Adaptimmune comienza un nuevo ensayo para el tratamiento del sarcoma sinovial.

Drug Discovery & Development - Julio 26, 2011

Adaptimmune ha iniciado en el Nacional Cancer Institute (NCI) un ensayo clínico piloto, abierto, en pacientes con sarcoma sinovial, a fin de probar su terapia con linfocitos T. Está planeado iniciar un segundo sitio en la Washington University  en el transcurso de este año.

Adaptimmune está concentrada en el uso de terapias con linfocitos T para tratar el cáncer, empleando dichos linfocitos para detectar y destruir a las células cancerosas. El ensayo ha sido diseñado para investigar la seguridad, el efecto antitumoral y la bioactividad de la infusión de células T del mismo paciente que han sido genéticamente modificadas para expresar una alta afinidad por el receptor de células T (TCR) específico para un determinado tipo de antígeno tumoral (proteína) conocido como antígeno CT (por su nombre en inglés).

Durante el ensayo, se empleará un receptor mejorado de células T a fin de hacer blanco en un antígeno CT denominado NYESO-1. La manufactura de las células T será efectuada en el Clinical Cell and Vaccine Production Facility en la Perelman School of Medicine, de la Universidad de Pensilvana.

En el ensayo se enrolarán hasta 10 pacientes, lo que puede llevar hasta 3 años para poder reunirlos debido a la rareza de la naturaleza de este cáncer. Además de evaluar la seguridad, el objetivo primario del estudio es determinar el índice de respuesta a la terapia. Los objetivos secundarios son investigar la persistencia de las células modificados genéticamente y  efectuar análisis de las respuestas antitumorales en los pacientes..

Publicado: Julio 25, 2011
Fuente: Adaptimmune Limited 

Buena actividad del davunetide en un ensayo de esquizofrenia precoz

Buena actividad del davunetide en un ensayo de esquizofrenia precoz

Drug Discovery & Development - Julio 20, 2011
Allon Therapeutics Inc. anunció que la administración de su producto líder daunetide durante 12 semanas parece prevenir el adelgazamiento cortical de importantes áreas del cerebro de pacientes esquizofrénicos.

El Dr. Bruce Morimoto, Vice-Presidente de Desarrollo de Drogas de Allon informó que “los nuevos datos son coherentes con el efecto neuroprotector ya hallado con davunetide en otros ensayos clínicos y confirman adicionalmente la estrategia que respalda al  estudio esencial de Fase 2/3 en parálisis supranuclear progresiva, actualmente en curso.”

El Dr. Morimoto informó que los nuevos datos surgieron de un análisis en curso efectuado con resonancia magnética (MRI) efectuado por un grupo de científicos y médicos liderados por el Dr. Jeffrey Lieberman, Jefe del Departamento de Psiquiatría de la Escuela de Medicina y Cirugía de la Universidad Columbia y Director del Instituto Psiquiátrico de Nueva York.

Así mismo agregó que “los nuevos datos mostraron que en los 23 pacientes en estudio, el grosor de la corteza en regiones específicas del cerebro decreció en 8 de los pacientes esquizofrénicos que recibieron placebo, en tanto que no mostró variaciones en los 15 enfermos tratados con davunetide; si bien estos datos se obtuvieron en un grupo relativamente pequeño en un estudio de carácter exploratorio, sugieren que el tratamiento con davunetide previene el adelgazamiento cortical hallado en la esquizofrenia”.

El Dr. Lieberman dijo que la esquizofrenia es una enfermedad neurodegenerativa en la que se considera que el adelgazamiento cortical es responsable de algunos de los síntomas clínicos, señalando que “en nuestro laboratorio hallamos que la corteza de pacientes esquizofrénicos es más delgada que la de voluntarios sanos. La extensión y el grado de adelgazamiento cortical en el estudio con davunetide es similar al que hemos visto previamente enfermos tratados con placebo”, agregando que la evidencia preliminar recogidad con el tratamiento con este nuevo fármaco es interesante y amerita la replicación en un estudio más amplio con este tipo de pacientes. Este nuevo hallazgo es consistente con la hipótesis r que el davunetide previene la atrofia cerebral por medio de un mecanismo que, según se cree, involucra la preservación de la función de los microtúbulos.”

El análisis mostró que el mayor efecto del tratamiento se halló en las regiones corticales dorsolaterales prefrontales y temporales del cerebro. Se sabe que estas áreas están involucradas en las alteraciones cognitivas asociadas con la esquizofrenia (CIAS).

Con anterioridaed, Allon ya había efectuado la presentación de datos basados en imágenes enfocadas a los cambios bioquímicos que subyacen detrás de los déficits cognitivos persistentes vistos en pacientes con esquizofrenia. Por ejemplo, el tratamiento con davunetide produjo un aumento estadísticamente significatio de la N-acetilaspartato (NAA), un marcador putativo de la integridad neuronal que se reduce en varios desórdenes neurovegetativas incluyendo la esquizofrenia.

El análisis de imágenes actualmente en curso es parte del estudio de recolección de datos, que a su vez es parte de un ensayo clínico más grande de Fase 2a, que había demostrado un efecto estadísticamente significaivo (p=0.015) sobre la medición de resultados funcionales, el denominado UPSA (University Performance-based Skill Assessment) de la Universidad de San Diego, en California.  El test de la UPSA evalúa la capacidad funcional de las habilidades para las actividades cotidianas y ha sido reconocido por las autoridades regulatorias como apropiado punto final compartido en pacientes que padecen CIAS.

Los estudios de imágenes están subvencionados por la National Alliance for Research on Schizophrenia and Depression (NARSAD) y por Allon. El estudio manejado por TURNS (Treatment Units for Research on Neurocognition and Schizophrenia), una red de ensayos clínicos conformado por ocho instituciones médicas académicas pertenecientes al National Institute of Mental Health (NIMH), parte de los U.S. National Institutes of Health.

Fecha de comunicación:: Julio 19, 2011
Fuente: Allon Therapeutics Inc. 

Varenicline Smokers at Risk of Heart Attack

Varenicline Smokers at Risk of Heart Attack
Drug Discovery & Development - July 05, 2011

Healthy, middle-aged smokers who take the most popular smoking cessation drug on the market have a 72%  increased risk of being hospitalized with a heart attack or other serious heart problems compared to those taking a placebo, a Johns Hopkins-led study suggests.
“People want to quit smoking to reduce the risk of cardiovascular disease but in this case they’re taking a drug that increases the risk for the very problems they’re trying to avoid,” says Sonal Singh, MD, MPH, an assistant professor of general internal medicine at the Johns Hopkins University School of Medicine and the lead author of the research.
In the study, Singh and his colleagues reviewed and analyzed 14 double-blind, randomized, controlled clinical trials involving more than 8,200 healthy people who received either varenicline (made by Pfizer and sold in the United States under the brand-name Chantix) or a placebo.
Whereas the number of people who died in each group was the same (seven), the increased risk of a major harmful cardiovascular event requiring hospitalization such as a heart attack or arrhythmia was 72% in the varenicline arms. The average age of study participants was less than 45 years and the majority were men.
Varenicline has been shown to modestly increase the chances of a successful quit attempt, compared to unassisted smoking cessation attempts. But overall, the majority of smokers who quit do so without any pharmaceutical assistance at all.
Singh notes that varenicline already carries a boxed warning—the Food and Drug Administration’s (FDA) highest level of caution—because of its association with suicidal thoughts and behaviors. “We notified the FDA of our cardiovascular safety concerns with Chantix earlier this year,” Singh says.
On June 16, the FDA announced that on the basis of a 700-person study, people with existing heart disease who use varenicline have a slightly increased risk of a heart attack or other cardiovascular event. But Singh’s study found that varenicline substantially increased the risk of a serious cardiovascular event even among smokers without heart disease. “I think our new research shifts the risk-benefit profile of varenicline,” Singh says. “People should be concerned. They don’t need Chantix to quit and this is another reason to consider avoiding Chantix altogether.”
Singh and his colleagues from Wake Forest University School of Medicine and the University of East Anglia in the United Kingdom emphasize the need to quit smoking, but suggest that varenicline may not be the right drug to kick the habit.
Singh says questions about the drug’s cardiovascular disease risks have been raised since varenicline went on the market in 2006, but no study has clarified the magnitude of these risks to the extent found in the new study. Singh says the FDA used a “fast-track” review process in allowing varenicline to be sold in the United States and would like regulators to take a new look.
The study was published in the Canadian Medical Association Journal.
Release Date: July 4, 2011
Source: Johns Hopkins University 

Vertex Hep C Treatment Passes Midstage Milestone

Vertex Hep C Treatment Passes Midstage Milestone
Drug Discovery & Development - March 31, 2011

CAMBRIDGE, Mass. (AP) - Vertex Pharmaceuticals Inc. said that a potential hepatitis C treatment was safe and tolerable in a midstage study.
The study involved a combination of telaprevir and VX-222 with pegylated-interferon and ribavirin and focused on people with genotype 1 chronic hepatitis C who were new to treatment. Pegylated-interferon and ribavirin are already used to treat hepatitis C.
Previously, the company halted other arms of its telaprevir and VX-222 study because the combination wasn't working.
Telaprevir is Vertex's primary drug candidate.
Date: March 31, 2011
Source: Associated Press

Phase 3 Study Begins for ALS Treatment

Phase 3 Study Begins for ALS Treatment
Drug Discovery & Development - March 31, 2011

Biogen Idec and Knopp Biosciences announced enrollment of the first patient in EMPOWER, a multi-national Phase 3 study evaluating the efficacy, safety and pharmacokinetics of dexpramipexole in patients with amyotrophic lateral sclerosis (ALS). ALS, also known as Lou Gehrig’s disease and motor neuron disease (MND), is a rapidly progressive and degenerative disease of motor neurons in the brain and spinal cord. It causes muscle atrophy and spasticity, resulting in weakness, progressive paralysis and ultimately death, usually by respiratory failure.
“ALS is a serious disorder that affects patients in the prime of life and for which there is an urgent need for new and effective treatments," said Merit Cudkowicz, M.D., MSc, Director of the MDA ALS Clinic at Massachusetts General Hospital and Principal Investigator in the EMPOWER study. "In the past several years, there has been an explosion of research in ALS that has helped us better understand the disease and potentially pave the way for the discovery and development of new treatments for ALS.”
EMPOWER is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multi-center study that will assess the safety and efficacy of dexpramipexole in people with familial or sporadic ALS. Approximately 804 patients will be randomized in a one-to-one ratio to receive either dexpramipexole 150 mg twice daily or placebo and will be followed for a period of at least 12 months. Investigators also have the option to maintain treatment with the current standard-of-care in ALS for all patients enrolled in the study. The primary objective will be assessed using a joint ranking of functional outcomes adjusted for mortality on the ALS Functional Rating Scale, Revised (ALSFRS-R), a validated rating instrument used by physicians for monitoring the progression of disability in patients with ALS.
“Biogen Idec is committed to working with the ALS community to find new treatment options for this deadly disease and to improve the lives of people with ALS,” said Alfred Sandrock, M.D., Ph.D., Senior Vice President of Development at Biogen Idec. “Based on promising data from earlier clinical trials, we believe that dexpramipexole has the potential to be a significant advance for people suffering from ALS, and we will fully explore its potential as a new treatment for this devastating disease.”
“Knopp Biosciences is very pleased to see dexpramipexole entering Phase 3 development with the initiation of the EMPOWER study,” said Michael Bozik, M.D., President and CEO of Knopp. “The promise of dexpramipexole has brought together a motivated multi-national network of investigators and study coordinators committed to determining if dexpramipexole can fulfill its potential as a treatment for patients with ALS.”
Dexpramipexole was well-tolerated in three Phase I studies in healthy volunteers who received dexpramipexole in single doses up to 300 mg or multiple doses of up to 150 mg twice daily for four-and-a-half days. Dexpramipexole was also well-tolerated in a two-part Phase II study (CL201) that evaluated about 100 ALS patients treated for up to nine months and in a subsequent Phase II extension study (CL211) that has continued to follow ALS patients for about two additional years. In the first part of CL201, dexpramipexole at 150 mg twice daily showed a trend toward slowing functional decline over a 12-week period compared to placebo. Following re-randomization in the second part of CL201, dexpramipexole at 150 mg twice daily again showed a trend toward slowing functional decline and also showed a trend toward improving survival compared to low dose over a six-month period. In CL201, the joint ranking, which incorporates both function and survival and which is the primary endpoint of the Phase 3 trial, significantly favored dexpramipexole 150 mg twice daily compared to 25 mg twice daily.
Biogen Idec has agreed with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for the design of the Phase 3 clinical trial of dexpramipexole. Under an SPA, the FDA evaluates a clinical trial protocol to assess whether it is adequate to meet current scientific and regulatory requirements for a potential application to market a new drug.
The first patient dosed in the EMPOWER study triggers a $10 million milestone payment from Biogen Idec to Knopp.
Date: March 31, 2011
Source: Biogen Idec http://www.biogenidec.com/

Clinical Trial Electronic Data Capture Solutions: Elevating Efficiency and Insight

Clinical Trial Electronic Data Capture Solutions: Elevating Efficiency and Insight
Simon Brooks, Senior Director Product Strategy, Oracle Health Sciences
Drug Discovery & Development - March 31, 2011

The clinical trial process has reached new levels of complexity. Trials are longer, more expansive, more complex in design, increasingly global, and require new types of data. These changes mean that investigative sites must grapple with more subjects, visits, forms, and data validation, as well as multiple applications. Trials are also more costly, driving the need for faster insight into trial and site progress so that sponsors can make more informed decisions about the path forward.
Electronic data capture (EDC) technology has become the de facto standard for gathering and recording clinical trial data. The technology has matured over the years to keep pace with these rapidly changing clinical trial requirements, but it is also important to keep pace with the increasing proficiency and expectations of EDC end users.
EDC solution providers are redoubling efforts to develop solutions that are more efficient for this new generation of front-line users and also expand data visibility to cover all areas of study progress. Helping trial managers and sponsors expedite collection analysis of all their clinical data allows deeper insights and more timely decisions, speeding the all-important time to market.
Helping the front-line
Improved efficiency and usability are key concerns for EDC users on the front lines of data collection and management. Clinical research professionals are looking for systems that do more than simply present data; they need solutions that quickly and easily direct them to key tasks and help complete them successfully—whether registering patients, managing and cleaning data, or monitoring.
EDC solution providers are working to answer this call.  For example, Oracle Health Sciences’ InForm GTM EDC solution has a redesigned user interface that helps users make quicker decisions, reduce errors and simplify navigation.
In creating the new InForm GTM interface, three usability design principles were applied:
• Signal-to-noise ratio, ensuring that important information stands out from peripheral information on a screen
• Information proximity, making certain that information needed to complete a task is grouped together on a screen for greater efficiency
• Streamlined workflow, simplifying the progression of documents and forms, as well as task delegation, from employee to employee or from sponsor to site
Leveraging these principles, InForm GTM’s interface features updated icons that make follow-up actions quicker to recognize and new controls that make it easier to navigate and filter. It also features improved query workflow that simplifies response exchange to speed query resolution; the user-friendly page layout also allows for more information to be viewed per page without scrolling.
Improving insight for managers and sponsors
With the cost of clinical trials continuing to escalate, study managers and sponsors need timely data on study progress to enable informed decisions about potential mid-study changes. Real-time reliable data and analytics are essential; InForm GTM provides on-demand and scheduled data extracts, as well as integrated advanced reporting that uses real-time data. These capabilities enable sponsors and managers to perform both ad hoc review and structured analysis earlier, and to more accurately spot trends and/or identify anomalies and move quickly to address them.
Electronic data capture solutions have hit their stride and are an indispensible clinical trial data management tool. A concerted focus to deliver expanded efficiency for front-line users—and real-time insight for trial managers and sponsors—will continue to fuel adoption and success.

Medicare to Cover Pricy Prostate Drug

Medicare to Cover Pricy Prostate Drug
Matthew Perrone
Drug Discovery & Development - March 31, 2011

WASHINGTON (AP) - Medicare officials said that the program will pay the $93,000 cost of prostate cancer drug Provenge, an innovative therapy that typically gives men suffering from an incurable stage of the disease an extra four months to live.
The Centers for Medicare and Medicaid said the biotech drug made by Dendreon Corp. is a "reasonable and necessary" medicine. The decision ensures that millions of men would be able to afford the drug through the government-backed health care coverage. With government reimbursement, analysts estimate Provenge could rack up $1 billion in sales next year. The decision, which will be finalized by June 30, is important for Dendreon because most prostate cancer patients are 65 or older.
Medicare is legally prohibited from considering price when deciding whether to pay for a new treatment. The Food and Drug Administration approved Provenge last April and in most cases Medicare automatically covers drugs cleared by the agency. But Medicare's decision to review Provenge last year prompted outrage from some patients and doctors who said the government was looking for a reason to avoid reimbursing for the pricey drug.
The infused drug is a first-of-a-kind treatment in that each dose is customized to work with a patient's immune system. Seattle-based Dendreon says Provenge's price reflects the more than $1 billion spent researching and developing the drug. And prostate cancer patients point out that the median survival time with Provenge is double that of chemotherapy, which is about two months and is marked by significant side effects.
"It's impossible to put a dollar figure on a human life, especially when you're talking about a drug that has such mild side effects," said Jim Kiefert, a prostate cancer patient and advocate who was part of the Provenge study. "Of all the treatments I've had - with surgery, radiation and hormone treatment - Provenge had fewer side effects than any of them."
But bioethicists who study health care decisions say Medicare's ruling on Provenge mirrors the bias of the overall U.S. health system, which emphasizes expensive treatments over basic medical care. Health care costs account for nearly one fifth of the U.S. economy, more than any other country.
"We tend to put our health care dollars into very high-tech interventions that produce very marginal improvements," said Dr. Steven Miles, a professor at the University of Minnesota's Center for Bioethics. "The problem is that we have created a health care system that is uniquely inadequate in terms of access to primary health care, which is where you get the most bang for your buck."
A growing number of biologically engineered cancer drugs are being priced in the $100,000 range, including therapies from Roche and Eli Lilly & Co. Last week, Bristol-Myers Squibb Co. received approval for a new melanoma drug that will be priced at roughly $120,000 per patient.
Provenge is the first FDA-approved cancer drug that uses the body's own immune system to fight the disease, offering an alternative to chemotherapy drugs that attack cancerous and healthy cells at the same time. The treatment is intended for men whose prostate cancer has spread elsewhere in the body and is not responding to hormone therapy or radiation.
Each regimen of Provenge must be tailored to the immune system of the patient using a time-consuming formulation process. Doctors collect special blood cells from each patient that help the immune system recognize cancer as a threat. The cells are mixed with a protein found on most prostate cancer cells and another substance to rev up the immune system, and then given back to the patient as three infusions two weeks apart.
Industry observers say much of the scrutiny of Provenge stems from the current political climate, as voters push lawmakers to cut the deficit and rein in government spending. At the same time, the new health care reform law has stoked debate about how much say the government should have in approving coverage of medical treatments.
Republicans have accused the acting chief of Medicare, Dr. Donald Berwick, of advocating health care rationing, based on statements he made as a professor at Harvard University. President Obama appointed Berwick to the post last year, but Senate Republicans have opposed his confirmation and have urged Obama to nominate someone else.
Dr. Sean Tunis, a former Medicare official, called Wednesday's decision a case of "the dog that didn't bark."
"You could almost guess that this would be outcome before they even started. So why raise all the anxiety and subject yourself to all the criticism of rationing?" said Tunis, who is director of the Center for Medical Technology Policy in Baltimore.
Medicare officials have said the agency's review of Provenge was aimed at clearing up bureaucratic confusion among Medicare carriers across the country, some of whom already pay for Provenge. Medicare on Wednesday called its online memo a "proposed decision," but it essentially amounts to agreeing to cover the drug for millions of seniors enrolled in its program.
Date: March 31, 2011
Source: Associated Press

Biolex Announces Hepatitis Trial Data

Biolex Announces Hepatitis Trial Data
Drug Discovery & Development - April 01, 2011

Biolex Therapeutics, Inc. announced that final 72-week results from its SELECT-2 Phase 2b trial of Locteron for the treatment of hepatitis C were presented at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.  Data presented show that Locteron achieved the SELECT-2 study objectives by demonstrating viral kinetics and response rates that were comparable with or exceeded the PEG-Intron control while also achieving a statistically significant reduction in flu-like adverse events, reduced rates of depression, lower use of concomitant medications and a reduced rate of discontinuation due to adverse events.  Locteron, the only controlled-release interferon alpha, is designed to offer key tolerability and dosing advantages over currently marketed interferons and serve as a core component of new combination therapies as the treatment of hepatitis C evolves to triple- and quad-drug regimens.
Locteron Dosing Convenience and Efficacy
Locteron is administered once every other week and requires half as many injections as the currently marketed interferons, each of which are injected once per week.  In SELECT-2, the sustained virologic response rate (SVR) for each of the three Locteron doses studied was comparable with or exceeded the response rate for the PEG-Intron control.
Locteron Tolerability Advantages
A major objective of the SELECT-2 trial was to further demonstrate the ability of Locteron’s controlled-release mechanism to improve patient tolerability.  In SELECT-2, patients treated with Locteron experienced a significant reduction in the frequency and severity of flu-like adverse events, reduced use of concomitant (analgesic/antipyretic) medications and reduced rates of depression compared to patients treated with the PEG-Intron control.
The SELECT-2 results were presented by the lead author, Eric Lawitz, MD, Medical Director and Principal Investigator, Alamo Medical Research, in a poster titled “SVR for Controlled-Release Interferon Alpha-2b (CR2b) + Ribavirin Compared to Pegylated Interferon Alpha-2b (Peg2b) + Ribavirin in Treatment-Naïve Genotype-1 (G1) Hepatitis C: Final Results from SELECT-2.”
“The results from the SELECT-2 trial are certainly consistent with the promise of this drug candidate as a next-generation interferon,” said Dr. Lawitz. “The ability of Locteron to contribute to the achievement of comparable viral cure rates with once-every-two-week dosing is a major improvement over current interferons.  I am also impressed by the consistency of the Locteron tolerability advantages seen across different outcome measures and reporting methodologies.  I look forward to seeing the development of Locteron expanded to testing in combination with direct-acting anti-viral agents.”
In SELECT-2, flu-like adverse events were predefined to include arthralgia, chills, fever, headache, and myalgia and were captured in two ways:
• Traditional weekly adverse event assessments performed by medical personnel at the clinical sites during the entire 48 weeks of treatment.
• Daily electronic patient reported outcome (ePRO) system where patients directly reported their flu-like adverse events each day for the first 12 weeks of the trial.
As the ePRO results were reported in real-time directly by the patients, they provide important insight into the patients’ real-world experiences with these side effects and the impact on their daily activities.  A comparison of the ePRO and clinic site reporting highlights the fact that flu-like adverse events may be even more important to patients than historically believed. The total flu-like adverse events reported directly by the patients using the ePRO system during the first 12 weeks of SELECT-2 were almost five times greater than the total flu-like adverse events recorded by the clinical sites.  Also of importance, patients rated 77% of their flu-like adverse events as moderate or severe in their ePRO reports, compared to the clinical site reporting in which only 16% of flu-like adverse events were rated as moderate or severe. Despite the apparent differences in sensitivity in the two adverse event reporting methods, the results from both the ePRO and weekly clinic visits complement each other and each demonstrates the substantial reduction in flu-like adverse events for patients treated with Locteron compared to patients treated with PEG-Intron.
“The ePRO results underscore the impact that flu-like adverse events have on patients’ daily lives and highlight the potential contribution of Locteron to the future success of multi-drug treatment combinations,” said Zobair Younossi, MD, Professor of Medicine and Executive Director of the Center for Liver Diseases at Inova Fairfax Hospital.  “Treatment of hepatitis C is likely to progress to triple and quad therapies in which interferons are combined with one or more direct-acting anti-viral drugs.  If confirmed in phase III clinical trials, Locteron’s potential advantages with regards to flu-like adverse events, depression and dosing frequency have the potential to enhance the overall tolerability of, and patient adherence to, these future combinations.”
Consistent with the reduction in flu-like adverse events, fewer Locteron patients used concomitant medications (analgesics and antipyretics) compared to PEG-Intron patients during the study period.
Date: March 31, 2011
Source: Polaris Group 

FDA Approves ADI-PEG 20 SPA

FDA Approves ADI-PEG 20 SPA
Drug Discovery & Development - April 01, 2011

Polaris Group announced that the U.S. Food & Drug Administration (FDA) has approved the company’s Special Protocol Assessment (SPA) for a Phase 3 clinical trial of pegylated arginine deiminase (ADI-PEG 20) in patients with advanced hepatocellular carcinoma (HCC). The randomized, placebo-controlled, global trial will enroll approximately 600 patients who have failed prior systemic chemotherapy. The primary endpoint of the study is overall survival.
Ghassan Abou-Alfa, M.D., of Memorial Sloan-Kettering Cancer Center in New York, is the principal investigator of the study.

“ADI-PEG 20 has demonstrated medical benefit in prior studies in multiple indications with a remarkable safety profile,” said Dr. Abou-Alfa. “I am delighted to lead this study to explore ADI-PEG 20 as a viable option for patients with advanced liver malignancies.”

SPA is a mechanism that allows the FDA and drug developers to reach an agreement prior to study initiation about the design and size of a Phase 3 trial. It will form the primary basis of an efficacy claim in a marketing application.
“The SPA agreement with the FDA is a key step in our plans for the clinical development of ADI-PEG 20,” said John Bomalaski, M.D., executive vice president, medical affairs, of Polaris. “We are pleased to move ADI-PEG 20 into a pivotal Phase 3 trial and to be working with such well-established hepatocellular carcinoma experts.”
Leo Chen, M.D., the lead investigator of the Phase 2 HCC study in Taiwan, stated, “Our Phase 2 study demonstrated that ADI-PEG 20 was effective and well-tolerated in patients with advanced liver cancer, and we look forward to the opportunity to further assess the efficacy and safety of this drug in a large randomized Phase 3 study.”

The lead investigator in China, Shukui Qin, M.D., president of the Chinese Society of Clinical Oncology and chair of the Chinese Liver Cancer Study Group, added, “Approximately half of the liver cancer-related deaths in the world are in China. We have been watching the development of this drug, and we are excited to become an active participant in this pivotal global study.”
ADI-PEG 20 is a biologic being developed to treat cancers carrying a major metabolic defect that renders them, unlike normal cells, unable to make arginine internally. Because arginine is one of the 20 amino acids that are essential for protein synthesis and survival of cells, these cells become dependent upon the external supply of arginine to survive and grow. ADI-PEG 20 works by systemically depleting the external supply of arginine and causes these arginine-dependent cancer cells to die while leaving the normal cells unharmed.

In addition to HCC, multiple other cancers have been reported to have a high degree of arginine-dependency. Early-to-mid-stage clinical trials have yielded positive results in patients with metastatic melanoma, and Phase 2 trials for small cell lung cancer (SCLC) and mesothelioma are currently ongoing. Polaris also plans to initiate clinical studies in prostate cancer, pancreatic cancer, leukemia, lymphoma and sarcoma this year.
Date: March 31, 2011
Source: Polaris Group 

BMS Releases HCV Study Results

BMS Releases HCV Study Results
Drug Discovery & Development - April 01, 2011

Bristol-Myers Squibb Company announced results from a Phase 2 clinical trial in which treatment with the investigational direct-acting antiviral (DAA) BMS-790052, an NS5A replication complex inhibitor, in combination with PEG-Interferon alfa and ribavirin (RBV), achieved sustained virologic response 12 weeks post-treatment (SVR12) in up to 92% of treatment-naïve patients chronically infected with hepatitis C (HCV) genotype 1 (10 mg dose arm, n=12). Adverse events and serious adverse events were consistent with those reported in the PEG-Interferon alfa and ribavirin arm and were comparable across all doses of BMS-790052. These data were reported today for the first time in a late-breaker poster session at the International Liver Congress, the 46th annual meeting of the European Association for the Study of the Liver (EASL) in Berlin, Germany.
“There currently exists a medical need for new medicines or new combinations of medicines for hepatitis C patients as many hepatitis C patients have limited success on the currently available treatments,” said Stanislas Pol, MD, PhD, Professor of Hepatology at Université Paris V (René Descartes), Paris, France and head of the Hepatology unit at Cochin Hospital, Paris, France. “The results of this study warrant further clinical investigation of adding Bristol-Myers Squibb’s investigational compound BMS-790052 to the current medicines to evaluate its potential to address this unmet treatment need.”
Date: March 31, 2011
Source: Bristol-Myers Squibb Company 

Sylatron Approved in Melanoma

Sylatron Approved in Melanoma
Drug Discovery & Development - April 01, 2011

The U. S. Food and Drug Administration approved peginterferon alfa-2b (Sylatron, Schering Corporation), for the treatment of patients with melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection including complete lymphadenectomy.
The approval was based on a single trial, EORTC 18991, an open label, multi-center trial enrolling 1256 patients.  Patients who had been adequately surgically resected for their primary cutaneous melanoma and affected regional lymph nodes were randomized (1:1) to receive either Sylatron or observation for a 5 year period. Stratification factors included type of nodal involvement (microscopic versus gross), number of positive nodes (1, 2-4, 5 or more, or not assessed), Breslow primary thickness (less than 1.5 mm, greater than or equal to 1.5 to 4 mm, greater than or equal to 4 mm), ulceration of primary tumor (present or absent or unknown), sex, and study center.  Patients were assessed for local and regional recurrence or distant metastases every three months for the first two years of treatment and subsequently every six months through the end of the trial.  An independent review committee, blinded to randomization assignment and to information that would break the treatment blind, reviewed the case report form data to determine the occurrence, and the date of loco-regional recurrence, or distant metastasis.
The primary efficacy endpoint, relapse-free survival (RFS), was defined as the time to the earliest of local or regional recurrence, distant metastases, or death. Based on 696 RFS events, an improvement in RFS for Sylatron-treated patients [hazard ratio 0.82 (95% CI: 0.71, 0.96); unstratified log-rank p = 0.011] was observed.  The estimated median RFS was 34.8 months (95% CI: 26.1, 47.4) and 25.5 months (95% CI: 19.6, 30.8) in the Sylatron and observation arms, respectively.  Following 525 deaths on study, there was no difference in overall survival between the Sylatron and the observation arms [hazard ratio 0.98 (95% CI: 0.82, 1.16)].
Safety was evaluated in 608 Sylatron-treated patients in EORTC 18991.  The most common (>60%) grade 1-4 adverse reactions experienced by Sylatron-treated patients were fatigue, increased ALT, increased AST, pyrexia, headache, anorexia, myalgia, nausea, chills, and injection site reactions.  The most common serious adverse reactions occurring in Sylatron-treated patients were fatigue, increased ALT, increased AST, and pyrexia.
Thirty-three percent of patients receiving Sylatron discontinued treatment due to adverse reactions.  The most common adverse reactions present at the time of treatment discontinuation were fatigue, depression, anorexia, increased ALT, increased AST, myalgia, nausea, headache, and pyrexia.  Five deaths were reported within 30 days of the last Sylatron dose.  Two were attributed to recurrent disease, two to cardiovascular disease possibly related to Sylatron, and one to an accident.
The recommended dose and schedule for Sylatron is 6 mcg/kg/week, subcutaneously for 8 doses, followed by 3 mcg/kg/week subcutaneously.  The maximum treatment period is 5 years (260 weeks).
Date: March 30, 2011
Source: U. S. Food and Drug Administration 

New Study into Possible Cholesterol-Autism Link

New Study into Possible Cholesterol-Autism Link
Drug Discovery & Development - April 01, 2011

Researchers at The Ohio State University Medical Center are studying whether simple nutritional intervention – adding cholesterol to the diets of children with autism spectrum disorders after a test to see if they need it – can improve core autism symptoms.
In excess, cholesterol can be harmful, but a certain amount is crucial for the proper development and maintenance of the brain. So it stands to reason that lower levels of cholesterol, particularly during crucial periods of growth, can lead to mental dysfunction, said principal investigator Dr. L. Eugene Arnold, a child psychiatrist at Ohio State’s Nisonger Center who specializes in researching and treating autism.
“We think low cholesterol may be contributing to the core autism symptoms of a subgroup of children with autism spectrum disorders,” said Arnold. “Cholesterol is not only in the food we eat, but we also make cholesterol, which is necessary for normal brain development and for the manufacture of vitamin D from sunlight. Vitamin D is necessary for brain development, so there are several possible ways that having low levels of cholesterol can affect the brain.”
Some children with autism appear to be typically developing before age 2 and then suddenly “regress,” losing language or social skills they had previously developed. Children with autism often have difficulty with pretend play, social interactions and verbal and nonverbal communication.
Researchers have noticed that cholesterol levels in children with autism spectrum disorders tend to be below the normal range compared to the general population. Normal or healthy cholesterol levels range from 120 to 190, but in up to 10 percent of children with autism, cholesterol levels are below 120, and in some cases, even below 100, Arnold said.
“The lower levels of cholesterol could be attributed to poor absorption or a missing enzyme to make the cholesterol,” said Arnold. “There are many different causes of autism, of course, from genetic through environmental, so what we’re investigating here will not apply to all children or people with autism, but it may help a subgroup.”
Too much cholesterol can do more harm than good, especially when it comes to cardiovascular health, so dosages will be closely monitored to find the optimal dose.
“It’s very important that we not just rush out and try to give everyone with autism more cholesterol, because for some of them it may be harmful,” Arnold said.
Ohio State’s Nisonger Center is teaming up with Dr. Elaine Tierney of Johns Hopkins University/Kennedy Krieger Institute and Dr. Forbes D. Porter of  the National Institutes of Health to conduct a phase I/II double-blind study for children ages 4-11 who have been diagnosed with autism spectrum disorders: autistic disorder, Asperger’s disorder, or pervasive developmental disorder – not otherwise specified (PDD-NOS).
Potential study participants will be screened, and 60 children who are found to have abnormally low cholesterol will participate in a 12-week double-blind study in which they will receive either the cholesterol or a placebo, followed by 12 weeks of “open” cholesterol supplementation.
The study, which is currently enrolling participants, is open to children with autism spectrum disorders who are ages 4-11.
Date: March 31, 2011
Source: The Ohio State University Medical Center 

Omeros OMS103HP Study Inconclusive

Omeros OMS103HP Study Inconclusive
Drug Discovery & Development - April 01, 2011

SEATTLE (AP) - Omeros Corp. said that its experimental knee drug did not meet goals of a late-stage clinical trial.
Omeros said it couldn't draw any conclusions about the drug's effectiveness in the study because of "confounding factors," or variables that made it impossible to tell if its drug was responsible for changes in the condition of patients. The company didn't elaborate on the nature of those factors.
Omeros was testing OMS103HP in patients undergoing arthroscopic surgery to reconstruct an anterior cruciate ligament. The anterior cruciate ligament is a major ligament in the knee, and Omeros' drug is intended to improve joint motion and function and reduce pain after surgery.
"Given the strength of the data from previous clinical studies of OMS103HP, we are obviously disappointed and surprised by the outcome," said Gregory A. Demopulos, M.D., Omeros Chairman and CEO. "As we learn more from our data analysis, we will provide additional information on our plans for OMS103HP."
Shares of Omeros plunged $3, or 37.5 percent, to $5 in aftermarket trading. The stock had the regular session up 20 cents at $8.
The company said the results don't show the drug is ineffective and do not undermine another late-stage study of OMS103HP in patients who are having surgery on the meniscus, a cartilage pad inside the knee.

FDA Extends Indacaterol Review

FDA Extends Indacaterol Review
Drug Discovery & Development - March 24, 2011

NEW YORK (AP) - The Food and Drug Administration is extending a review of a lung disease drug made by Novartis AG, the Swiss drugmaker said Wednesday.
Novartis said the FDA now expects to complete its review in July instead of April. It said the FDA needs more time to review data from clinical trials, but has not asked for any new information. The agency is reviewing Novartis' application on a drug candidate called QAB149, or indacaterol, which is a once-per-day treatment for patients with chronic lung conditions like bronchitis or emphysema.
Indacaterol is a bronchodilator, or a drug that opens up airway passages in the lungs to ease breathing.
In February, an FDA advisory panel recommended the drug be approved. Novartis is seeking approval to market the drug in strengths of 75 micrograms and 150 micrograms per day. The company said the drug is approved under the name Onbrez Breezhaler in more than 50 countries. Onbrez Breezhaler is marketed in strengths of 150 micrograms and 300 micrograms per day.
Date: March 23, 2011
Source: Associated Press

Gene Therapy Improves Parkinson's Symptoms

Gene Therapy Improves Parkinson's Symptoms
Maria Cheng
Drug Discovery & Development - March 24, 2011

LONDON (AP) - An experimental treatment improved symptoms of Parkinson's disease in a mid-stage test, echoing results of an earlier pilot study.
The new research is the first to show positive results in a test of gene therapy against a sham operation in about three dozen U.S. Parkinson's patients.
After six months, those who got the gene therapy scored 23 percent better on a standard test to measure motor skills while those who got the sham operation did about 13 percent better.
"Gene therapy is no longer just a theory," said Michael Kaplitt, a neurosurgeon at New York-Presbyterian Hospital and Weill Cornell Medical Center, and one of the study authors. "We are getting much closer to a reality where this treatment can be offered to patients." Kaplitt said the results might spur similar treatments for other brain disorders like Alzheimer's, epilepsy and depression.
Kaplitt and colleagues tested the gene therapy on 16 people while 21 others received a sham surgery. The patients were aged 30 to 75 and all were taking Parkinson's medication.
In patients with Parkinson's disease, their brains get overactive after losing the normal supply of a chemical called GABA. The new treatment, gene therapy, works by inserting billions of copies of a gene into patients' brains that helps them produce more GABA.
For patients who got the gene therapy, doctors drilled a hole into their brains while they were still awake. Doctors then slipped in a virus engineered to bring in billions of copies of a gene to help the brain pump out more GABA. Patients who didn't get the gene therapy had holes drilled halfway into their skull - enough to trick them they were getting the therapy but apparently not enough to do any harm.
The study was published online Thursday in the journal, Lancet Neurology. It was paid for by Neurologix Inc., the biotechnology company that devised the therapy. Kaplitt is a company cofounder and holds stock options and many of the other authors reported ties to Neurologix and other pharmaceuticals.
Parkinson's disease is a degenerative brain illness that causes problems including tremors, rigidity and slow movements. It affects about one in every 500 people. There is no cure, but some drugs help control symptoms.
"This is promising research but we need to know how long these benefits of gene therapy might last," said Michelle Gardner, research development manager at Parkinson's U.K. She was not linked to the study. "We don't know if there could be long-term consequences of introducing viruses into the brain."
In an accompanying commentary in the Lancet, Michael Hutchinson of New York University School of Medicine questioned whether gene therapy offers any advantages over deep brain stimulation, which has been used to treat Parkinson's disease for about a decade.
Walter Liskiewicz, a former oral surgeon in Michigan with the disease, could barely move before receiving the gene therapy in 2009 as part of the experiment.
Now, he plays jazz music and recently returned from a holiday in Brazil. "Everything was taken away from me and to just have them handed back is pretty special," he said. "It's like a miracle."
Date: March 23, 2011
Source: Associated Press

Symphogen Receives U.S. Patent on Lead Cancer Compound

Symphogen Receives U.S. Patent on Lead Cancer Compound
Drug Discovery & Development - March 07, 2011

Symphogen, a private biopharmaceutical company developing antibody therapeutics, has been granted a U.S. patent for Sym004 as well as other antibody compositions containing at least two distinct anti-EGFR antibodies having certain binding characteristics. The U.S. Patent and Trademark Office on February 15, 2011 issued to the company U.S. Patent No. 7,887,805, titled “Recombinant anti-epidermal growth factor receptor antibody compositions.” The US patent provides protection through 2028. Patent applications are pending in additional countries.
In addition, Symphogen said that preclinical data demonstrating the superiority of the now proprietary Sym004 to the reference monoclonal antibody (mAb) was highlighted  in Paris, France in a Plenary Session of the 9th International Symposium on Targeted Anticancer Therapies (TAT Symposium). Sym004 is a novel drug candidate based on a 1:1 mixture of two anti-EGFR monoclonal antibodies (mAbs) directed against distinct non-overlapping epitopes in EGFR extracellular domain III.
Preclinical data showed Sym004, a novel and proprietary candidate for the treatment of solid tumors, exhibited more pronounced growth inhibition in vitro and superior efficacy in in vivo models as compared to the reference anti-EGFR mAb cetuximab. The rate at which Sym004 induced rapid and efficient removal of the ligand-binding receptor from the cancer cell surface by triggering EGFR internalization and degradation was reported to have exceeded that of cetuximab. Like anti-EGFR mAbs in current clinical use, Sym004 has been previously shown to inhibit cancer cell growth and survival by blocking ligand-binding receptor activation and downstream signaling.
The preclinical safety and pharmacokinetic data for Sym004 has been accepted for a poster presentation at the upcoming 102nd Annual meeting of the American Association for Cancer Research in Orlando, Florida April 2-6, 2011.
Later this year, Symphogen plans to present safety data from its first clinical study of Sym004. Sym004 is currently being evaluated for the treatment of advanced solid tumors with particular focus in patients with KRAS wildtype advanced metastatic colorectal cancer (mCRC) that have previously progressed to standard chemotherapy and marketed anti-EGFR mAbs. A phase I-II, first-in-human study is presently ongoing at centers in USA and Spain. The main objective of the phase I component of the trial is to evaluate the safety and tolerability of multiple ascending doses of Sym004 in patients with solid tumors. The phase II part of the trial will include patients with mCRC and begin in the first quarter of 2011.

Date: March 7, 2011
Source: Symphogen  

Primary Endpoints Met In Phase 3 Trial of Tofacitinib

Primary Endpoints Met In Phase 3 Trial of Tofacitinib
Drug Discovery & Development - March 07, 2011

Pfizer Inc. announced that the ORAL Sync Phase 3 study (A3921046) of tofacitinib (development code: CP-690,550), formerly known as tasocitinib, an investigational, novel, oral JAK inhibitor, being studied in moderate-to-severe rheumatoid arthritis (RA), met its primary endpoints by showing statistically significant changes versus placebo in reducing signs and symptoms of RA, as measured by ACR20 response rates at six months; in improving physical function, as measured by mean change in HAQ DI at three months; and in reaching DAS28-4(ESR) <2.6 at six months. The safety profile of tofacitinib was consistent with that seen previously in the clinical program, and no new safety signal was detected. A full analysis of efficacy and safety data will be submitted to a future scientific meeting.
ORAL Sync evaluated the efficacy and safety of tofacitinib doses 5 mg and 10 mg given twice daily compared to placebo in patients with moderately to severely active RA who had a previous  inadequate response to a DMARD and who continued to receive background traditional DMARD therapy throughout the study.
Tofacitinib is a novel, oral Janus kinase (JAK) inhibitor that is being investigated as a targeted immunomodulator and diseasemodifying therapy for RA. More than 4,000 RA patients have been treated with tofacitinib in clinical trials to date. Unlike current therapies for RA, which are directed at extracellular targets such as pro-inflammatory cytokines, tofacitinib takes a novel approach, targeting the intracellular signaling pathways that operate as hubs in the inflammatory cytokine network. The Phase 3 ORAL Trials clinical program includes six studies with more than 350 locations in 35 countries worldwide.
Date: March 4, 2011
Source: Pfizer 

NeuroVive Conducting Late-Stage NeuroSTAT Trial

NeuroVive Conducting Late-Stage NeuroSTAT Trial
Drug Discovery & Development - March 08, 2011

NeuroVive has signed an agreement with the European Brain Injury Consortium (EBIC) to conduct a European multi-center Phase 2/3 clinical trial of NeuroSTAT for neuroprotection in patients with traumatic brain injury (TBI). The goal of the collaboration is to secure the highest possible study quality and compliance with clinical standards to support NeuroSTAT‘s rapid progress toward commercialization. To this end, NeuroVive will work closely with EBIC’s key European experts in the field of neurotrauma and acute brain injuries.
NeuroVive will manage the study in close collaboration with the EBIC group and a clinical research organization (CRO) to be selected. The collaboration with EBIC includes development of the study protocol, site selection, patient recruitment, and statistical support. This adaptive design Phase II/III study will determine the safety and efficacy of NeuroSTAT in moderate to severe TBI.
TBI is a leading cause of death and disability among a predominantly young male population, mostly victims of motor vehicle accidents. TBI is composed of two stages: a first stage of initial brain damage; and a second stage of mitochondrial collapse inside brain cells leading to additional cell death, brain damage and disability. The active agent in the NeuroSTAT formula is a proven mitochondrial protector that in animal studies is a potent neuroprotectant against TBI. There are over 10 million TBI cases per year worldwide. Annually in the U.S., head trauma sends two million people to the emergency room and a half a million have injuries severe enough to be admitted to the hospital. TBI kills 50,000 people and leaves 80,000 people disabled. The annual market for an effective TBI drug is estimated to exceed US$1 billion in the U.S. and Europe.
NeuroVive CEO Mikael Bronnegard comments: ”We are very pleased to collaborate on the NeuroSTAT Phase II/III clinical trial with a highly respected organization like EBIC, comprising key opinion leaders and medical experts in the field of neurotrauma in Europe. Through this collaboration, we have an excellent opportunity to advance the development of NeuroSTAT toward clinical use in treating millions of TBI patients worldwide.”
Professor Andrew Maas, Chairman of EBIC, Professor and Chairman Department of Neurosurgery at University Hospital Antwerp, Belgium comments: “This clinical trial is of great interest to us. The need for international collaboration in the conduct of research in the clinical management of head injury has never been greater, but rigorous evaluation must be carried out on a range of approaches that include new pharmacological agents. Therefore, the collaboration with NeuroVive in conducting a clinical trial in TBI patients with their product NeuroSTAT offers a unique way to address all critical issues in study design, selection of end-points, patient recruitment, study monitoring and, finally, study analysis.”
Date: March 3, 2011
Source: NeuroVive 

Toxikon Completes Kevetrin Toxicity Studies

Toxikon Completes Kevetrin Toxicity Studies
Drug Discovery & Development - March 08, 2011

Toxikon Corp., a pre-clinical contract research organization with facilities in the US and in Leuven, Belgium, has completed toxicity studies in two species for Cellceutix Corp.’s Kevetrin, a compound the Beverly, Mass.-based firm is developing for the treatment of resistant lung and breast cancers.  Toxikon also performed safety pharmacology studies of Kevetrin in the central nervous system as well as the cardiovascular and respiratory systems.
The toxicity studies, required for an Investigational New Drug (IND) filing, involved administering Kevetrin to two species of animals weekly over a 29-day period. In each study, there was a 14-day recovery period after the dosing. Parameters measured were hematology, clinical chemistries, weight change, food consumption, survival, urinalysis, ophthalmic examination and histopathology. The studies are designed to confirm that Kevetrin meets FDA safety requirements for clinical studies in humans.
 “We are proud to have led these important toxicology studies and help Cellceutix achieve its goal of getting Kevetrin to human trials and, ultimately, to market,” said Dr. Laxman Desai, president and CEO of Toxikon, adding that “Toxikon is equipped to meet the industry’s anticancer and antiviral drug discovery demands.”
“Along with safety studies, we can assist with synthesis of intermediates from milligrams to hundreds of grams,” said Dr. Desai, the former director of anti-cancer drug research at Boston’s Dana Farber Cancer Institute. “We are also poised to develop small novel molecules for the treatment of cancer and viral diseases.”
“We are very delighted with the results of the toxicity studies performed at Toxikon,” said Dr. Krishna Menon, Chief Scientific Officer at Cellceutix.  “While we were confident that the results would be positive, it is always reassuring to see the actual results.  We are also grateful to Toxikon for the high quality of their work and excellent customer focus.  We have now taken a major step forward toward our phase 1 clinical trial, to be conducted at a major cancer center in the Boston area.”
In animal studies, Kevetrin was found to significantly delay tumor growth in multi-drug resistant lung, breast and colon cancer cell lines. In data presented in April, 2010 at the American Association for Cancer Research, the efficacy of Kevetrin in a mouse model of drug resistant lung cancer was shown to increase with increasing dose. The data presented at the AACR also show that the administration of a second cycle of therapy with Kevetrin in the same animal model continues to delay tumor growth without the development of resistance.
Date: November 2, 2010
Source: Toxikon Corp. 

FDA Reviewing Carbinoxamine XR NDA

FDA Reviewing Carbinoxamine XR NDA
Drug Discovery & Development - March 09, 2011

Tris Pharma, a specialty pharmaceutical company that develops innovative drug delivery technologies, announced that the US Food and Drug Administration (FDA) has accepted its Extended Release Carbinoxamine Oral Suspension NDA for the treatment of allergies in kids two years and older. If approved, Tris Pharma's Extended Release Suspension will provide an alternative to the currently available immediate release formulations.
Carbinoxamine is a mildly sedating antihistamine with years of proven safety and efficacy. Prior to 2006 carbinoxamine was widely used, with more than 100 marketed Carbinoxamine containing products including extended release solid dose and combination products. However, nearly all of these were older products which hadn't gone through the FDA's rigorous approval process. Following the 2006 DESI review, the FDA removed all carbinoxamine based products with the exception of two immediate release formulations which had been reviewed, creating a void for patients and doctors who valued the benefits associated with an extended release formulation.
A leading New York based pediatrician, Dr. Laura Garabedian, who often prescribes Carbinoxamine said, "I've always found Carbinoxamine extremely effective in treating allergy symptoms in children but don't typically prescribe it as first line therapy because the existing immediate release formulations need to be dosed multiple times per day including a dose while the child is in school thus making compliance poor.  I am looking forward to a true 12 hour formulation that tastes good.  The new product profile should translate to improved compliance and better outcomes."
Ketan Mehta, Tris President and CEO added, "This is the fourth NDA submission based on Tris' OralXR+ technology platform including Nexiclon XR, a recently launched first ever 24-hour liquid Extended Release Suspension. Tris' pipeline includes several additional products targeted for the respiratory market, i.e. cough, cold, allergy therapies and are slated for submission over the next two years. Tris plans to launch Carbinoxamine Extended Release Suspension in 2012 season and is currently evaluating its options including partnering with other specialty Pharma companies. "
Date: March 9, 2011
Source: Tris Pharma 

New Leukemia Treatment Given Orphan Drug Status

New Leukemia Treatment Given Orphan Drug Status
Drug Discovery & Development - March 09, 2011

Stemline Therapeutics, Inc. announced that SL-401, the Company's lead compound, has received Orphan Drug designation from the U.S. Food and Drug Administration (FDA) for the treatment of acute myeloid leukemia (AML).
SL-401 has completed a multi-center Phase 1/2 clinical trial in AML where it has demonstrated single agent efficacy, including two durable complete responses (CRs), multiple blast reductions and disease stabilizations, and an overall survival (OS) benefit in heavily pre-treated patients. SL-401 was well-tolerated and bone marrow-sparing. The trial results were presented at the 52nd Annual Meeting of the American Society of Hematology (ASH) in December 2010. SL-401 is now poised for Phase 3 clinical trials in patients with advanced AML.
Stemline's CEO, Ivan Bergstein, MD, noted, "Receipt of Orphan Drug designation represents another key milestone in the advancement of SL-401 through the regulatory process. We are also very encouraged by the potential of SL-401 to benefit patients with advanced stage AML, an unmet medical need, as well as additional hematologic malignancies including MDS, CML and potentially certain lymphomas."
Date: March 9, 2011
Source: Stemline Therapeutics, Inc.

Sildenafil Reduces Raynaud's Frequency in lcSSc

Sildenafil Reduces Raynaud's Frequency in lcSSc
Drug Discovery & Development - March 09, 2011

Researchers in Europe reported that treatment with modified-release sildenafil significantly reduced the frequency of attacks of Raynaud's phenomenon in patients with limited cutaneous systemic sclerosis (lcSSc), also known as scleroderma. The double-blind, placebo-controlled trial found that sildenafil was well tolerated with only some subjects experiencing minor or moderate side effects. Full findings are available in the March issue of Arthritis & Rheumatism, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology (ACR).
Raynaud's phenomenon (RP) is a major feature of systemic sclerosis and causes the blood vessels supplying the skin surface to spasm in response to cold temperatures or stress. These vasospasms can affect the fingers, toes, ears and other skin surfaces and can lead to serious complications in patients with systemic sclerosis such as digital ulceration, soft tissue or bone infection, or gangrene. According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) this phenomenon occurs in 90% of all scleroderma cases.
The multicenter trial of sildenafil was conducted in 57 men and women (ages18-75) with Raynaud's secondary to lcSSc between January and June 2003. For one to two weeks prior to the start of treatment, patients recorded the number of RP attacks. To be eligible for the study, subjects had to report at least 7 RP attacks per week. RP was defined as an episode where fingers or toes turned white (pallor) followed by blue (cyanosis) and/or red (erythema) in response to cold or emotion. At the onset of the treatment phase, participants were randomized in a one-to-one ratio, receiving either 100 mg of modified-release sildenafil for three days followed by a 200-mg modified-release dose daily for 25 days, or placebo for 28 days. Researchers used a two-step dosing to enhance tolerability, and a modified-release formulation to permit once daily dosing.
"Our findings indicate that modified-release sildenafil reduced the frequency of Raynaud's attacks in patients with systemic sclerosis," confirmed lead author, Ariane Herrick, M.D., from the University of Manchester in the U.K. Results showed a 44% reduction in attacks per week (from baseline to day 28) for subjects receiving sildenafil treatment compared with 18% in the placebo group. Researchers also reported that the mean number of attacks per week improved from 30.5 at baseline to 18.7 after sildenafil treatment, compared with 25.0 at baseline to 19.3 after placebo treatment.
Secondary endpoints, including Raynaud's Condition Score, duration of attacks, and RP pain score, were not significantly different between the two groups. The most frequent adverse events reported were headache and indigestion with the majority of these events being mild or moderate. Researchers did not observe any serious adverse events. Dr. Herrick concluded, "Modified-release sildenafil was well tolerated and reduced the attack frequency in patients with Raynaud's secondary to lcSSc. Our results, coupled with existing medical evidence of the favorable safety profile of sildenafil in non-SSc patient populations, may offer a beneficial treatment option in lcSSc patients with secondary Raynaud's."
Date: March 8, 2011
Source: Arthritis & Rheumatism

No Clear Evidence of Increased Efficacy In RA Treatment

No Clear Evidence of Increased Efficacy In RA Treatment
Drug Discovery & Development - March 09, 2011

A recent trial of rituximab in combination with a tumor necrosis factor (TNF) inhibitor and methotrexate (MTX) in patients with active rheumatoid arthritis (RA) found the safety profile to be consistent with other RA trials with TNF inhibitors. While the trial reported no new safety risks, clear evidence of an efficacy advantage in RA patients receiving the combination therapy was not observed in this study sample. Results of the trial are published in the March issue of Arthritis & Rheumatism, a peer-reviewed journal of the American College of Rheumatology.
The National Arthritis Data Workgroup estimates that 1.3 million U.S. adults have RA which is characterized by systemic joint inflammation that often leads to joint damage, functional impairment and significant disability. While MTX is successfully used to treat many RA patients, the severity of the disease in some patient populations requires the use of additional disease-modifying antirheumatic drugs (DMARDs). A specific group of biologic DMARDs, called tumor necrosis factor (TNF) inhibitors and includes such therapies as etanercept and adalimumab, block the immune system response, and have been shown to be safe and effective in clinical trials.
Prior studies, however, have found that up to 40% of RA patients exhibit an inadequate response, intolerance, or inadequate slowing of the rate of joint damage with biologic therapies, and require additional treatment options. "Our objective was to assess the safety of the biologic DMARD, rituximab, in combination with a TNF inhibitor and MTX in patients with active RA," said lead study author Maria Greenwald, M.D., from Desert Medical Advances in California. This was a small exploratory study to evaluate safety with this combination due to the prolonged effect of rituximab, and the fact that RA patients may switch to an alternate biologic such as a TNF inhibitor before the effects of rituximab may have resolved.
The controlled trial enrolled 51 patients with active RA (more than 5 swollen and tender joints) who were receiving a stable dose of MTX (10-25 mg/week) and either etanercept or adalimumab for more than 12 weeks. Participants were randomized 2:1 to receive one course of rituximab or placebo (two 500-mg doses intravenously or placebo). The primary study end point was the proportion of patients developing more than one serious infection through week 24.
Researchers reported one serious infection (pneumonia) in the rituximab group compared with none in the placebo group (TNF only) at week 24. Nonserious infections were reported in 18 patients (55%) and 11 patients (61%) in the rituximab and placebo groups, respectively. Infections requiring intravenous antibiotics occurred in three patients administered rituximab and in none of the patients receiving placebo. No life-threatening, opportunistic, fungal or tuberculosis infections were observed. Dr. Greenwald noted, "The incidence of serious infections was low."
During the 24-week trial period the overall proportion of patients in the placebo and rituximab cohorts who experience an adverse event (AE) was 83% and 94%, respectively. The most common AEs reported in the rituximab group included nausea, pruritus (itching sensation), and fatigue. In the placebo group the common AEs included upper respiratory tract infections, sinusitis, headache, and exacerbation of RA. Two serious adverse effects (SAEs)—pneumonia and coronary artery occlusion—were observed in two rituximab-treated patients; no SAEs were reported in patients receiving placebo.
The research team also determined the percentage of patients achieving an ACR201 improvement response at week 24 was 30% in the rituximab group compared with 17% in the placebo group. ACR50 responses achieved in the rituximab and placebo groups were 12% and 6%, respectively. "The safety of rituximab in combination with a TNF inhibitor and MTX was consistent with other RA trials of rituximab and MTX that did not include TNF inhibitors," concluded Dr. Greenwald. The authors noted that a larger study examining efficacy of treatment of RA using multiple biologic DMARDs is underway.
Date: March 8, 2011
Source: Arthritis & Rheumatism

Biotron Completes First Part of Phase 2 Trial

Biotron Completes First Part of Phase 2 Trial
Drug Discovery & Development - March 10, 2011

Australian drug development company Biotron Limited has completed stage one of a landmark human trial of its lead Hepatitis C drug candidate, BIT225.
Twelve patients have been dosed in the first half of the trial being undertaken by ACLIRES, an international contract research organisation (CRO) that specialises in running antiviral drug clinical trials.  All are infected with the most common strain of the Hepatitis C virus, genotype 1.
The second half of the trial - which also involves 12 patients - is now underway and expected to be completed in May, with results anticipated to be analysed and released in June.  The trial is blinded, so no results are available until samples are analysed at the conclusion of the trial and the data is unblinded.
Biotron CEO, Dr Michelle Miller, said the trial was proceeding as expected and the results would be "of international interest".
She said BIT225 was a first-in-class drug candidate which specifically targeted the p7 protein, a viral protein essential to virus production and replication.
"We are happy with how the trial is progressing.  We achieved the necessary ethics and drug import approvals to move to the second stage of the trial, which is now underway."
Twelve further patients are now being recruited and dosed over four weeks with BIT225.
As in stage one of the study, one-third of patients are being given a placebo, one-third a dose of 400mg BIT225 and another one -third are being dosed at 200mg BIT225.
This Phase 2 trial is examining how BIT225 works in combination with current approved treatments for HCV, Interferon and Ribavarin.
Existing drugs have limited effectiveness and can be toxic.  Doctors say fifty per cent of sufferers do not respond to current therapies, signalling a need for new treatments that directly target and halt replication and reproduction of the virus.
Date: March 9, 2011
Source: Biotron Limited www.biotron.com.au/

Lucentis Trial Shows Greatly Improved Vision in DME

Lucentis Trial Shows Greatly Improved Vision in DME
Drug Discovery & Development - March 10, 2011

Genentech, a member of the Roche Group, announced that two-year results from a pivotal Phase 3 trial (RISE) showed patients with diabetic macular edema (DME) who received Lucentis (ranibizumab injection) experienced rapid and sustained improvement in vision compared to those who received a placebo (sham) injection. According to the data, there was:
• A significantly greater number of people able to read at least 15 additional letters on the eye chart compared to baseline after 24 months (primary endpoint),
• Significant improvement in average eye chart reading scores at 24 months,
• Significant improvement in average eye chart reading scores demonstrated as early as seven days,
• Significantly decreased retinal swelling.
“There are no FDA-approved medicines to treat DME and these new data add to evidence showing that Lucentis can help improve vision soon after initiation of treatment,” said Dennis M. Marcus, M.D., Southeast Retina Center in Augusta, Ga., who presented the data today. “In the case of the RISE study, the significant improvements on day seven were maintained for two years.”
DME is an eye condition characterized by swelling of the retina, which can occur in patients with type 1 or type 2 diabetes and can cause blurred vision, severe vision loss and blindness. DME is a leading cause of blindness among the working-age population in most developed countries. The safety results were consistent with previous experience and no new adverse events related to Lucentis were observed in the study.
The data from RISE, the first of two pivotal Phase 3 studies of Lucentis in DME, were presented at the 34th Annual Macula Society Meeting in Boca Raton, Fla.
Date: March 10, 2011
Source: Genentech 

BioTox Using eStudy for Preclinical Studies

BioTox Using eStudy for Preclinical Studies
Drug Discovery & Development - March 10, 2011

iAdvantage Software, Inc., a leading solutions provider for managing development and pre-clinical life science studies, announced that BioTox Sciences (BTS), a GLP Contract Research Organization, headquartered in San Diego, California, is deploying the eStudy hosted solution to manage its GLP and Non-GLP preclinical/nonclinical studies.
In 2010, BioTox Sciences expanded its resources from people to facility to accommodate growing Sponsors' needs. The final challenge was selecting a software platform that would handle the different preclinical study types BTS conduct's today, yet flexible enough to meet the ever-changing needs they may encounter as they continue to grow.
"After weighing our options and careful due diligence, BioTox Sciences chose to implement eStudy, by iAdvantage Software," commented Tareq Abu-Nadi, BioTox Sciences, Business Development/Study Director. "eStudy will complement and streamline the study processes conducted at BTS by increasing productivity and speed of reporting while maintaining 21 CFR parts 58 and 11 compliance."
"eStudy's flexibility ensures that BTS Study Directors would be able to use eStudy on various projects and multiple species. Whether a typical 28 day toxicity study in rats or dogs, or a long term surgery study in NHPs, eStudy will be used to manage the study, capture the data and allow for on-demand reporting of results upon Sponsor request. This significant investment gives us the ability to produce complete study books in mere hours, and help Sponsors make key decisions on development of compounds and initiate more projects," concluded Abu-Nadi.
eStudy is a 100% web-based study management platform that iAdvantage Software hosts for BTS at Cegidem/Dendrite's world-class network operating center in Chesapeake, VA. "eStudy will continually grow with BioTox Sciences, easily adapt to new study-types, marry to BTS' operational work-flow and interface with 3rd party instruments and tools," stated Diana Michelotti, Director of Marketing and Sales for iAdvantage. "eStudy implemented for BTS, provides BTS with a custom fit solution without the start-from-scratch price."
Date: March 9, 2011
Source: iAdvantage Software, Inc. 

FDA Approves Taxotere Generic

FDA Approves Taxotere Generic
Drug Discovery & Development - March 10, 2011

LAKE FOREST, Ill. (AP) - Drug and medical device maker Hospira Inc. said the Food and Drug Administration approved the company's generic version of Sanofi-Aventis' blockbuster cancer drug Taxotere.
The company said its generic Taxotere, or docetaxel, is a single-vial formulation as opposed to the two-step process for the branded Taxotere.
Hospira said Taxotere, which is approved to treat breast, lung, and other types of cancer, had U.S. sales of about $1.2 billion in 2010. It lost patent protection in November, opening the market up to generic competitors.
Shares of Hospira have traded between $48.69 and $60.49 over the last 52 weeks.
Date: March 9, 2011
Source: Associated Press

FDA Approves First Lupus Treatment in Half-Century

FDA Approves First Lupus Treatment in Half-Century
Matthew Perrone
Drug Discovery & Development - March 10, 2011

WASHINGTON (AP) - The Food and Drug Administration approved the first new drug to treat lupus in over 50 years, a milestone that medical experts say could prompt development of other drugs that are even more effective in treating the debilitating immune system disorder.
Known as Benlysta, the injectable drug is designed to relieve flare-ups and pain caused by lupus, a little-understood and potentially fatal ailment in which the body attacks its own tissue and organs.
Biotech drugmaker Human Genome Sciences Inc. spent 15 years developing Benlysta and will co-market it with GlaxoSmithKline PLC.
The companies estimate there are at least 200,000 lupus patients in the U.S. who could benefit from the drug.
But experts stress that Benlysta is not a miracle drug: It only worked in 35 percent of North American patients tested and was not effective for patients with the deadliest form of the disease. Additionally, it did not show positive results in African-Americans, who are disproportionately affected by lupus.
FDA said in its news release it would require the drug developers to conduct another study exclusively on African-Americans.
Dr. Betty Diamond, who has studied lupus for 30 years, said Benlysta should provide encouragement to researchers and drug developers.
"It will send out the message that it's possible to conduct a successful clinical trial in lupus and that's tremendously important to keep the pharmaceutical industry interested in this disease," said Diamond, a researcher at the Feinstein Institute in New York.
Janice Fitzgibbon of McLean, Virginia has been taking Benlysta for two years as part of the drug's clinical trial program.
"It's given me my life back," she said, after being so crushed by pain that she couldn't take her dog for a walk or drive her children to school.
"It's a bittersweet thing for me because I have friends with lupus for whom this drug won't work," said Fitzgibbon, who is 54. "There's no one-size-fits-all for lupus and I'm just extremely fortunate that my lupus is mild and is helped by Benlysta."
FDA approved the drug for systemic lupus erythematosus, the most common form of the disease. Ten-year survival for patients diagnosed with the illness is more than 85 percent, according to the National Institutes of Health.
Lupus patients have long struggled to draw attention to their disease, which affects women nine times more than men. African-Americans are three times more likely to have the disease.
"I don't think there's a conspiracy here, but it just hasn't gotten a lot of funding and it hasn't gotten a lot of attention from the media," said Dr. Abby Abelson, chair of the Department of Rheumatologic and Immunologic Disease at the Cleveland Clinic.
Lupus causes fibrous tissue and inflammation of internal organs, skin rashes and joint pain. Most of Benlysta's benefit came from relieving muscle inflammation versus organ problems, as measured on a comprehensive checklist of lupus symptoms.
The disease occurs when the body's protector cells, known as antibodies, stop differentiating between foreign invaders, like bacteria, and healthy cells. The cause of this malfunction is not understood.
Currently most patients treat their disease with a variety of drugs that help ease inflammation, including painkillers, steroids and antimalarial drugs - which were first approved for lupus in the 1950s. Many patients say the side effects of those treatments are nearly as uncomfortable as the disease itself. Steroids can cause bone fractures, weight gain and infection.
Wednesday's approval completes a remarkable turnaround for Maryland-based Human Genome Sciences which has been developing Benlysta since 1996 and has no other products on the market. The company originally tested Benlysta, known generically as belimumab, as a treatment for rheumatoid arthritis.
When a mid-stage trial in lupus patients failed to meet researchers' goals in 2006, many analysts wrote the drug off and downgraded the company's stock. But when scientists reanalyzed the data they found that the drug helped block the antibodies that cause lupus symptoms in a subset of patients.
Analysts estimate the drug could reach annual sales exceeding $3 billion within five years.
Date: March 9, 2011
Source: Associated Press

Vertex Drug Improves Lung Function

Vertex Drug Improves Lung Function
Drug Discovery & Development - February 23, 2011

CAMBRIDGE, Mass. (AP) - Vertex Pharmaceuticals Inc. said that its potential cystic fibrosis drug improved lung function in a key late-stage study.
The company said VX-770 prompted a 10.5 percent improvement in lung function in the study, which focused on patients with a specific gene mutation. The drug is aimed at treating the genetic cause of the lung condition, rather than just symptoms. But, its target is a small swath of cystic fibrosis patients with a specific gene mutation.
Cystic fibrosis causes a fluid imbalance in the lungs, resulting in mucus plugging, infection and inflammation. It affects about 30,000 people in the U.S. and around 70,000 people worldwide, the company has said. The study focused on patients with the G551D mutation and about 4 percent of the U.S. cystic fibrosis population has at least on copy of the mutation.
Vertex said the drug also met secondary goals of improving the symptoms of the condition, which include shortness of breath and difficulty breathing.
"Treating the underlying cause of cystic fibrosis with VX-770 led to clinical improvements that were far beyond our expectations, providing support for an entirely new approach to the treatment of this disease," said Peter Mueller, executive vice president of global research and development and chief scientific officer at Vertex.
He said the company plans on working with regulatory agencies to determine the fastest path for approval of VX-770. Vertex expects data from another late-stage study in mid-2011. The company plans on asking for regulatory approval in the U.S. and Europe in the second half of 2011.
Date: February 22, 2011
Source: Associated Press

Tibotec Launches Two Phase 3 Trials for TMC435

Tibotec Launches Two Phase 3 Trials for TMC435
Drug Discovery & Development - February 24, 2011

Tibotec Pharmaceuticals announced that two global, registrational phase 3 trials are recruiting patients to examine TMC435, its investigational hepatitis C protease inhibitor, in treatment-naïve adults with chronic genotype 1 hepatitis C virus (HCV). A third global phase 3 trial is being conducted in genotype 1 HCV patients who have experienced a viral relapse after prior interferon-based treatment. Approximately 3.2 million people in the U.S. live with chronic hepatitis C disease and more than 170 million people have the disease globally. The response-guided trials will compare the efficacy, safety and tolerability of TMC435 given as a single 150 mg oral tablet once daily for 12 weeks versus placebo; each patient also will be treated with a background regimen of peginterferon and ribavirin for 24 or 48 weeks.
“TMC435 is an important component of our growing HCV pipeline,” said Brian Woodfall M.D., Vice President of Global Clinical Development at Tibotec. “The initiation of the TMC435 phase 3 clinical trial program reinforces our commitment to develop innovative new treatment options that may decrease the duration of treatment for patients with chronic hepatitis C infection.”
The first global, phase 3, double-blind, randomized study, known as TMC435-C208 or QUEST-1 (QD dosing of TMC435 of previoUsly untreated GEnotype 1 patienTs-1), will evaluate a single TMC435 once-daily oral tablet (150 mg) versus placebo in treatment-naïve HCV patients. Both groups will also receive peginterferon alfa-2a (Pegasys) and ribavirin (Copegus) as part of their treatment. The second global, phase 3, double-blind, randomized study, known as TMC435-C216 or QUEST-2 (QD dosing of TMC435 of previoUsly untreated GEnotype 1 patienTs-2), also will evaluate a single TMC435 once-daily oral tablet (150 mg) versus placebo in treatment-naïve HCV patients. However, patients in this trial will either receive peginterferon alfa-2a (Pegasys) and ribavirin (Copegus) or peginterferon alfa-2b (PegIntron) and ribavirin (Rebetol) as part of their treatment. A third global, phase 3, double-blind randomized study, known as TMC435-C3007 or PROMISE (PROtease inhibitor TMC435 In PatientS who have previously rElapsed on IFN/RBV), will evaluate a single TMC435 once-daily oral tablet (150 mg) verses placebo in HCV patients who experienced viral relapse after previous interferon-based therapy. Both groups will receive peginterferon alfa-2a (Pegasys) and ribavirin (Copegus). The complete treatment duration for all three trials will be 24 or 48 weeks, depending on patient response.
The studies will be conducted at more than 160 sites in 24 countries, including the U.S. and countries throughout Europe, and together seek to enroll approximately 1,125 HCV genotype 1 infected patients who are treatment-naïve or have experienced a relapse after previous interferon-based HCV therapy. To be eligible, patients must have chronic hepatitis C infection, and must have had a liver biopsy within three years of the screening visit. For those patients who have not had a liver biopsy in the three years prior to the study, one will be performed before the baseline visit. In addition, eligible patients need to have completed a recent ultrasound with no findings suspicious of hepatocellular carcinoma (HCC). Patients with signs of hepatic decompensation, liver disease of any non-HCV etiology, co-infection with hepatitis B or HIV-1 and 2 or a history of malignancy within 5 years of the screening vitis are ineligible for the study. Patients in QUEST-1 and QUEST-2 trials must not have received any prior treatment for hepatitis C, and patients in the PROMISE trial must have previously received at least 24 weeks of (peg)interferon-based therapy, along with documented negative HCV RNA at last on-treatment measurement, and have relapsed (detectable HCV RNA) within one year of last taking medication. The primary endpoint of the studies is to assess whether TMC435 is superior to placebo in achieving sustained virologic response (SVR), defined as HCV RNA <25 IU/ml undetectable, 24 weeks after the planned end of treatment (SVR 24), with the final analysis being performed after the last patient reaches week 72 of the study. Secondary endpoints include superiority of TMC435 versus placebo at 12 weeks (SVR 12), after planned end of treatment and at week 72 of the study. Evaluations of viral breakthroughs, relapse rates in treatment groups, safety and tolerability also will be assessed.
Phase 3 studies for TMC435 also recently launched in Japan.
Date: February 18, 2011
Source: Tibotec Pharmaceutical