Previous Issues

Newsletter Archive

By Deepen Joshi, Sunovion Pharmaceuticals

J&J Drug Receives EMA Approval for Metastatic Prostate Cancer

The European Medicines Agency (EMA) has approved J&J's Zytiga (abiraterone acetate), a novel, once-daily, oral, androgen biosynthesis inhibitor. Abiraterone acetate is approved, in combination with prednisone or prednisolone, for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen. Metastatic castration-resistant prostate cancer, or mCRPC, occurs when cancer has metastasized (spread) beyond the prostate and disease progresses despite serum testosterone below castrate levels. In 2008, an estimated 370,000 new cases of prostate cancer were diagnosed in Europe, and nearly 90,000 men died from the disease.

"The European Commission approval of abiraterone acetate gives new hope to men who are suffering from this late stage of prostate cancer with very few treatment options left," said Professor Karim Fizazi, Department of Cancer Medicine, Institut Gustave Roussy, France, who was an investigator in the abiraterone acetate pivotal Phase 3 study. "The efficacy, safety and ease of use of abiraterone acetate, a medicine that can be taken at home, will address an important unmet medical need for many patients, helping them to live longer with a better quality of life and less pain."

Abiraterone acetate is an androgen biosynthesis inhibitor that inhibits the CYP17 enzyme complex which is required for the production of androgens. Androgens (e.g. testosterone) are hormones that promote the development and maintenance of male sex characteristics. However, in prostate cancer, androgens can fuel the tumor's growth. Androgen production primarily occurs in the testes and adrenal glands but, in men with prostate cancer, the tumor tissue is an additional source of androgens. Abiraterone acetate is the first oral treatment for metastatic castration-resistant prostate cancer that inhibits androgen production at all three sources.

"In patients who have exhausted standard treatment options, including chemotherapy, abiraterone acetate offers a novel, well tolerated option for treating this devastating disease," explained Professor Johann S. de Bono, MD, FRCP, MSc, PhD, The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust, and one of the co-lead investigators for the Phase 3 clinical study. "In Europe, prostate cancer is the third most common cause of cancer deaths so it is essential that new treatments options like abiraterone acetate are developed." (Source: J&J Website, 7 September, 2011)

New Generic Lovenox Receives FDA Approval

California biotech Amphastar Pharmaceuticals won FDA permission to sell a generic version of the blockbuster drug Lovenox, following a years-long battle that was unusually bitter even for the high-stakes world of drug approvals. Lovenox, known generically as enoxaparin, is a rapid-acting version of heparin, the widely used blood thinner critical to millions of heart patients.

The approval could shake up the multbillion-dollar-a-year market for a drug widely used in heart patients, hurting Lovenox maker Sanofi SA and Momenta Pharmaceuticals, a company that started selling a generic version of Lovenox last year in partnership with Sandoz, a unit of Novartis AG.

Branded Lovenox's global revenue was $4.28 billion in 2010, but it fell to $1.5 billion in the first half of this year, according to Sanofi. Momenta said in an earnings call in August that generic Lovenox had generated over $1 billion since its launch in the fall of 2010.

Amphastar has agreed with leading generics maker Watson Pharmaceuticals to co-market generic Lovenox in the US. Amphastar was the first company to apply to make enoxaparin, filing for approval at the FDA in 2003. Momenta/Sandoz followed two years later.

As the FDA's consideration of both companies' applications dragged on for years, Amphastar complained that the FDA was biased toward Momenta. It cited the FDA's unexpected decision in November 2007 to add a specialized safety-testing requirement for all applicants seeking to sell generic Lovenox. That requirement put Amphastar back at the same starting point as Momenta and came after Momenta's founder, a MIT scientist, lobbied the head of the FDA's drug division for tougher approval standards for drugs like generic Lovenox. The FDA has repeatedly denied any favoritism and Momenta has said it was also delayed by the new testing requirement.

In 2008, the Momenta founder was given a leading role by FDA officials in a high-profile agency task force investigating the source of heparin contamination from China linked to 81 deaths in the US. When the task force said it identified the contaminant in the Chinese supplies, Momenta's stock price rose. Meanwhile, Amphastar's application was on hold, because one of its Chinese suppliers was linked to a contaminated heparin batch, leading to numerous FDA inspections of Amphastar facilities, according to the company.

In the fall of 2010, a report by the Government Accountability Office, Congress's watchdog agency, said FDA actions involving heparin-related issues had contributed to a public perception of bias toward Momenta and risked the agency's integrity. The FDA said it should have been more careful about the appearance of conflict of interest.

Amphastar sued the FDA after the agency approved Momenta's application in July 2010, saying the FDA illegally quarantined Chinese heparin needed for its drug development. The agency said it acted appropriately; the suit is pending.

A third company seeking to sell generic Lovenox, Teva Pharmaceutical Industries, the world's top-selling maker of generic drugs, hasn't received its approval from the FDA yet, a company spokeswoman said. (Source:  Alicia Mundy, Wall Street Journal, 20 September 2011)

FDA Reorganizes Area Responsible for Review of Drugs for Cancer Therapy

The FDA has announced organizational changes within the office responsible for reviewing all drug and biologic applications for cancer therapies. The Center for Drug Evaluation and Research's (CDER) Office of Oncology Drug Products has been reorganized and renamed the Office of Hematology and Oncology Products (OHOP).

The previous structure contained three divisions: Division of Hematology Products (DHP), Division of Drug Oncology Products (DDOP), and Division of Biologic Oncology Products (DBOP). The new structure contains four divisions: Division of Hematology Products (DHP), Division of Oncology Products 1 (DOP1), Division of Oncology Products 2 (DOP2), and Division of Hematology Oncology Toxicology (DHOT).

Unique features of the reorganization include the creation of DOP1 and DOP2, the agency's primary review divisions for cancer solid tumor therapies, and the creation of DHOT, which will review nonclinical information. (Source: FDA Website, 12 September, 2011)

FDA approves Alexion's Soliris for Rare Pediatric Blood Disorder

The FDA has approved Soliris (eculizumab) to treat patients with atypical Hemolytic Uremic Syndrome (aHUS), a rare and chronic blood disease that can lead to kidney (renal) failure and is also associated with increased risk of death and stroke. Atypical HUS accounts for 5 to 10 percent of all cases of hemolytic uremic syndrome. The disease disproportionately affects children.

This new indication for Soliris is being approved with an extension of the existing Risk Evaluation and Mitigation Strategy (REMS), to inform health care professionals and patients about the known risk of life-threatening meningococcal infections.

Soliris will continue to be available only through a restricted program, and prescribers must enroll in a registration program and provide a medication guide to patients who receive the drug.

Soliris was reviewed under the FDA's priority review program, which provides for an expedited six-month review of drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists. (Source: FDA Website, 23 September, 2011)

FDA Approves Remicade for Ulcerative Colitis in Children 6 Years and Older 

The FDA has approved Remicade (infliximab) to treat moderately to severely active ulcerative colitis (UC) in children 6 years and older who have had inadequate response to conventional therapy. Remicade reduces signs and symptoms of UC and induces and maintains clinical remission in these patients. Remicade is manufactured by Janssen Biotech Inc. in Malvern, PA.

UC is a type of inflammatory bowel disease (IBD) that affects the lining of the large intestine (colon) and rectum. Symptoms of UC include abdominal pain, diarrhea, rectal bleeding, weight loss and fever. Between 50,000 and 100,000 children in the United States have IBD; of these, 40 percent have UC. 

Remicade carries a Boxed Warning for risk of serious infections and cancer. Increased risks of infections include tuberculosis and infections caused by viruses, fungi or bacteria. There have been cases of unusual cancers reported in adolescent and young adult patients using TNF-blocking agents, including a rare and fatal type of cancer called Hepatosplenic T-cell Lymphoma.

Children should have all of their vaccines brought up to date before starting treatment with Remicade and should not receive live vaccines while taking Remicade. The most common side effects of Remicade are worsening of UC, upper respiratory infections, infusion-related reactions, and headache. (Source: FDA Website, 23 September, 2011)

FDA Seeks Comment on Streamlined Review of Lower Risk, New Technology, Devices 

The FDA has issued draft guidance for manufacturers that updates and streamlines the de novo review process used for certain innovative, low to moderate-risk medical devices that do not meet the requirements for clearance under the better-known 510(k) review process.  

Before manufacturers may market most low to moderate-risk medical devices, such as certain catheters or diagnostic imaging devices, they must obtain FDA "clearance" of a premarket notification or 510(k), named after the section of federal law that describes this notification requirement. Generally, 510(k) submissions must demonstrate that the new device is substantially equivalent to another, legally marketed medical device that is also low to moderate-risk. However, some low to moderate-risk medical devices are novel and not comparable to an already legally marketed device. Legislation passed by Congress in 1997 created the de novo process for these types of devices. 

The draft guidance outlines a pathway for a concurrent 510(k) and de novo petition without duplicative data requirements, trimming up to 90 days from the process and fostering more efficient, early interaction between manufacturers and the FDA. It also provides clarity for manufacturers on the suitability of a device for the de novo process. 

This draft guidance is one of 25 action items listed in the FDA's Plan of Action for Implementation of 510(k) and Science Recommendations launched earlier this year to improve the predictability, consistency and transparency of the agency's pre-market review programs. (Source: FDA Website, 30 September, 2011)

New FDA Transparency Report Outlines Proposals for Enforcement Data, For Public Comment

The FDA has released eight new draft proposals in a report titled "Food and Drug Administration Transparency Initiative: Draft Proposals for Public Comment to Increase Transparency by Promoting Greater Access to the Agency's Compliance and Enforcement Data." These draft proposals are focused on making FDA's compliance and enforcement data more accessible and user-friendly, and they are part of FDA's ongoing efforts to increase the transparency of FDA's operations and decision-making. 

In developing these draft proposals, FDA met with the Environmental Protection Agency (EPA) and the Department of Labor (DOL), both of which have well-developed and well-regarded enforcement data.  At these meetings, EPA and DOL shared their insights to help FDA learn from, and build upon, their experiences.  Like FDA, EPA and DOL recognize that transparency can drive good behavior and promote regulatory compliance.

FDA Commissioner Dr. Margaret Hamburg launched FDA's Transparency Initiative in June 2009.  The initiative is overseen by a Task Force that includes key leaders of FDA.  The report issued today advances that initiative and is part of FDA's response to President Obama's Presidential Memorandum on Regulatory Compliance, which directed federal agencies to make compliance information more publicly available, easily accessible, downloadable and searchable online. (Source: FDA Website, 03 October, 2011)

FDA Works to Improve Science Used to Approve Medical Devices

The FDA's Center for Devices and Radiological Health (CDRH) has released a report highlighting scientific activities that support the medical device industry and product development, while maintaining the safety and effectiveness of the products. The report, "Regulatory Science in FDA's Center for Devices and Radiological Health: A Vital Framework for Protecting and Promoting Public Health," offers a look at the work FDA engages in every day to help foster science that enables and supports innovation and sound medical product development.

Regulatory science efforts cited in the report range from providing device designers with computer modeling of cardiovascular devices to developing standard tests for the durability and performance of spinal disc implants. The document is intended to give clinicians, researchers, patient groups and the medical device industry an idea of the scope of the scientific activities at CDRH and how they support device innovation and protect public health.

Investments in regulatory science help to maintain a robust medical device industry by reducing the time and resources needed to develop, assess and test new products. This can lead to quicker, more efficient device approvals, potentially decrease the size and duration of premarket clinical trials, and speed the rate at which breakthrough technologies reach the market. In August, the FDA released its "Strategic Plan for Regulatory Science." That plan touches on several priority areas identified in greater detail in CDRH's regulatory science report. (Source: FDA Website, 03 October, 2011)

FDA Awards Three Grants to Stimulate Development of Pediatric Medical Devices 

The FDA has announced the awards of three grants to boost the development and availability of medical devices for children. A panel of five experts with experience in medicine, business, and device development reviewed 10 applications for the grants, which will be administered by the FDA's Office of Orphan Products Development.

Children differ in terms of size, growth, and body chemistry and present unique challenges to device designers. In addition, the activity level and ability to manage some implantable or long-term devices may vary greatly among children. While this program is administered by the Office of Orphan Products Development, it is intended to encompass devices used in all pediatric diseases, not just rare diseases.

Legislation passed by Congress in 2007 established funding for grants to nonprofit groups to help stimulate projects to promote the development and availability of pediatric medical devices. These grants are meant to encourage the development of multiple pediatric device projects. While a small portion of the grants fund specific projects, the real spirit of this grant program is to provide information clearinghouses to promote multiple projects.

As part of the legislation, each of the grant recipients will coordinate among the FDA, device companies, and the National Institutes of Health's Eunice Kennedy Shriver National Institute of Child Health and Human Development to facilitate research and any necessary applications for device approval or clearance. (Source: FDA Website, 03 October, 2011)

FDA Outlines Plans for an Outside Network of Scientific Experts

FDA's Center for Devices and Radiological Health (CDRH) is soliciting comment on a plan to create a network of outside scientific experts who would provide staff with rapid access to specific specialized knowledge about emerging technology, as well as other topics. To further enrich this comment period, CDRH will also conduct a 12-week pilot of the network through December 30, 2011.

CDRH has a world-class scientific staff that includes scientists, engineers, and clinicians. Nevertheless, there are times when staff must turn to external sources to further enhance their scientific understanding, given the rapid advancements in certain scientific fields, the development of pioneering technologies and increasingly complex medical devices.

The CDRH Network of Experts would allow CDRH staff to tap into a vetted network of scientists and engineers for detailed scientific information on topics related to medical devices.

CDRH will build the Network in partnership with leading scientific, academic and clinical organizations. The center will enter into agreements with these organizations and then call upon their membership for needed expertise.  This will permit a fast and efficient exchange of knowledge with scientific leaders on an as-needed basis. (Source: FDA Website, 04 October, 2011)

FDA Approves Gel to Stop Blood Flow during Blood Vessel Surgery

The FDA has approved LeGoo, a gel that allows surgeons to temporarily stop blood flow during surgery so that they can join blood vessels without clamps or elastic loops. LeGoo is manufactured by PluroMed Inc. of Woburn, MA.

To join blood vessels during surgery, it is necessary to temporarily stop blood flow to the area where a new vessel is being attached. Stopping blood flow prevents flooding the surgical area with blood, which makes it difficult for the surgeon to clearly see where to place sutures to connect the two vessels.

LeGoo is a temperature sensitive gel that is liquid at room temperature and solid at higher temperatures. When injected into a blood vessel, LeGoo forms a gel plug that molds to the shape of the blood vessel and stops blood flow for up to 15 minutes. After the blood vessels are joined, the plug is expected to dissolve on its own in 15 minutes. In the event the plug needs to dissolve sooner, the surgeon can dissolve the gel plug by applying a cold pack or cold saline to the blood vessel.

LeGoo is approved for temporarily stopping blood flow in blood vessels below the neck that are 4 millimeters or less in diameter. It is contraindicated for use on vessels supplying blood to the brain. (Source: FDA Website, 04 October, 2011)

FDA Commissioner Outlines Steps to Spur Biomedical Innovation, Improve Health

FDA Commissioner Margaret A. Hamburg, M.D. has released a blueprint containing immediate steps that can be taken to drive biomedical innovation, while improving the health of Americans. Titled "Driving Biomedical Innovation: Initiatives for Improving Products for Patients," the blueprint addresses concerns about the sustainability of the medical product development pipeline, which is slowing down despite record investments in research and development.
   
While FDA has long been committed to promoting innovation with a number of efforts underway already this year, Dr. Hamburg recognized the need to create an FDA-wide framework to address the changing scientific landscape. This blueprint launches the Innovation Initiative, identifying additional steps the agency can take immediately to address the most pressing concerns facing patients and industry.
 
The report's proposals stem from a review of FDA's current policies and practices, as well as months of meetings with major stakeholders nationwide, including key industry leaders, small biotech, pharmaceutical and medical device company owners, members of the academic community and patient groups. (Source: FDA Website, 05 October, 2011)

FDA Approves Cialis to Treat Benign Prostatic Hyperplasia

The FDA has approved Cialis (tadalafil) to treat the signs and symptoms of benign prostatic hyperplasia (BPH), a condition in which the prostate gland becomes enlarged, and for the treatment of BPH and erectile dysfunction (ED), when the conditions occur simultaneously. Cialis was approved in 2003 for the treatment of ED and is manufactured by Indianapolis-based Eli Lilly and Co.

Common symptoms of BPH include difficulty in starting urination and a weak urine stream; a sudden urge to urinate; and more frequent urination including at night. The FDA has approved eight other drugs to treat symptoms of BPH: Proscar, (finasteride), Avodart (dutasteride), Jalyn (dutasteride plus tamsulosin), and the alpha blockers: Hytrin (terazosin), Cardura (doxazosin), Flomax (tamsulosin), Uroxatral (alfuzosin) and Rapaflo (silodosin). (Source: FDA Website, 06 October, 2011)

FDA Approves Juvisync, First Combination Drug to Treat Type 2 Diabetes and High Cholesterol in One Tablet

The FDA has approved Juvisync (sitagliptin and simvastatin), a fixed-dose combination (FDC) prescription medication that contains two previously approved medicines in one tablet for use in adults who need both sitagliptin and simvastatin.

About 20 million people in the United States have type 2 diabetes, and they often have high cholesterol levels as well. These conditions can lead to increased risk of heart disease, stroke, kidney disease and blindness, among other chronic conditions, particularly if left untreated or poorly treated. 

Juvisync is approved with a Medication Guide that provides important information to patients. The most common side effects of Juvisync include upper respiratory infection; stuffy or runny nose and sore throat; headache; muscle and stomach pain; constipation; and nausea. (Source: FDA Website, 07 October, 2011)

FDA Approves Ferriprox to Treat Patients with Excess Iron

The FDA has approved Ferriprox (deferiprone) to treat patients with iron overload due to blood transfusions in patients with thalassemia, a genetic blood disorder that causes anemia. Patients with thalassemia have excess iron in the body from frequent blood transfusions, a condition that is serious and can be fatal. These patients also have a risk of developing liver disease, diabetes, arthritis, heart failure or an abnormal heart rhythm. Ferriprox is marketed by ApoPharma of Toronto, Canada.

The standard of care to treat transfusional iron overload is chelation therapy - chemical agents that are used to remove heavy metals from the body. Ferriprox is intended for use when chelation therapy is inadequate.

The therapy is being approved under the FDA's accelerated approval program, designed to provide patients with earlier access to promising new drugs followed by further studies to confirm the drug's clinical benefit. ApoPharma has agreed to several post-marketing requirement and commitments. One commitment includes further study of the use of Ferriprox in patients with sickle cell disease who have transfusional iron overload. (Source: FDA Website, 14 October, 2011)

Unique features of the reorganization include the creation of DOP1 and DOP2, the agency's primary review divisions for cancer solid tumor therapies, and the creation of DHOT, which will review nonclinical information. (Source: FDA Website, 12 September, 2011)

FDA Outlines Plans for an Outside Network of Scientific Experts for CDRH

FDA's Center for Devices and Radiological Health (CDRH) is soliciting comment on a plan to create a network of outside scientific experts who would provide staff with rapid access to specific specialized knowledge about emerging technology, as well as other topics. To further enrich this comment period, CDRH will also conduct a 12-week pilot of the network through December 30, 2011.

CDRH has a world-class scientific staff that includes scientists, engineers, and clinicians. Nevertheless, there are times when staff must turn to external sources to further enhance their scientific understanding, given the rapid advancements in certain scientific fields, the development of pioneering technologies and increasingly complex medical devices.

The CDRH Network of Experts would allow CDRH staff to tap into a vetted network of scientists and engineers for detailed scientific information on topics related to medical devices.

CDRH will build the Network in partnership with leading scientific, academic and clinical organizations. The center will enter into agreements with these organizations and then call upon their membership for needed expertise.  This will permit a fast and efficient exchange of knowledge with scientific leaders on an as-needed basis. (Source: FDA Website, 04 October, 2011)