Previous Issues

by Deepen Joshi

FDA Launches Medical Device and Radiation-Emitting Product Website

The FDA has launched the Center for Devices and Radiological Health (CDRH) Transparency Website as part of the agency's transparency initiative. The site will provide information about medical device and radiation-emitting product regulatory processes and decisions, and summaries of data that provide the rationale for agency actions.

The new website is part of an ongoing effort within CDRH, across the FDA and across the Department of Health and Human Services to enhance public communication and transparency. CDRH's previous site provided information about approved products, industry guidance, medical device safety, and adverse event reports. On the new site, this and additional information are displayed in a more user-friendly format. The site includes information related to the following topics:

• Premarket submissions for approved and cleared products
• Postmarket performance and safety
• Compliance and enforcement
• Science and research
• Educational resources
• CDRH performance data

The site also features a searchable Total Product Life Cycle database, which integrates premarket and postmarket medical device information from multiple data sources into a single snapshot. In the coming months, FDA will expand the CDRH Transparency Web site to include premarket approval and clearance reviews. (Source: FDA Website, 19 April, 2010)

FDA Approves a Cellular Immunotherapy for Advanced Prostate Cancer

The FDA has approved Provenge (sipuleucel-T), a new therapy for certain men with advanced prostate cancer that uses their own immune system to fight the disease. Provenge, manufactured by Seattle-based Dendreon Corporation, is indicated for the treatment of asymptomatic or minimally symptomatic prostate cancer that has spread to other parts of the body and is resistant to standard hormone treatment.

Prostate cancer is the second most common type of cancer among men in the US, behind skin cancer, and usually occurs in older men. In 2009, an estimated 192,000 new cases of prostate cancer were diagnosed and about 27,000 men died from the disease, according to the National Cancer Institute.

Provenge is an autologous cellular immunotherapy, designed to stimulate a patient's own immune system to respond against the cancer. Each dose of Provenge is manufactured by obtaining a patient's immune cells from the blood, using a machine in a process known as leukapheresis. To enhance their response against the cancer, the immune cells are then exposed to a protein that is found in most prostate cancers, linked to an immune stimulating substance. After this process, the patient's own cells are returned to the patient to treat the prostate cancer. Provenge is administered intravenously in a three-dose schedule given at about two-week intervals. (Source: FDA Website, 29 April, 2010)

FDA Approves Genzyme's Lumizyme for Treatment of Late-Onset Pompe Disease

The FDA has approved Genzyme's Lumizyme (alglucosidase alfa) for patients ages 8 years and older with late-onset (non-infantile) Pompe disease, a rare genetic disorder that occurs in an estimated 1 in every 40,000 to 300,000 births. Its primary symptom is heart and skeletal muscle weakness, progressing to respiratory weakness and death from respiratory failure. Lumizyme is manufactured at Genzyme facilities in Ireland and Belgium.

In Pompe disease, a gene mutation prevents the body from making an enzyme, or making enough of the enzyme called acid alpha-glucosidase (GAA), necessary for proper muscle functioning. GAA is used by the heart and muscle cells to convert a form of sugar called glycogen into energy. Without the enzyme action, glycogen builds up in the cells and, ultimately, weakens the heart and muscles. Lumizyme is believed to work by replacing the deficient GAA, thereby reducing the accumulated glycogen in heart and skeletal muscle cells.

Lumizyme is being approved with a risk evaluation and mitigation strategy (REMS). It will only be available through a restricted distribution system called the Lumizyme ACE (Alglucosidase Alfa Control and Education) Program to ensure that it is used by the correct patient group. Lumizyme will carry a Boxed Warning because of the risk of anaphylaxis, severe allergic reactions, and immune-mediated reactions.

Currently, the only other treatment for Pompe disease available in the US is Myozyme, which is also manufactured by Genzyme at its manufacturing facilities in Framingham and Allston. Myozyme has been in short supply due to limited manufacturing capacity. The manufacturer reserved Myozyme to treat infants and children with Pompe disease because younger patients generally have a much more aggressive form of the disease. (Source: FDA Website, 25 May, 2010)

FDA Approves Amgen's Prolia for Treatment of Osteoporosis

The FDA has approved  Prolia, an injectable treatment for postmenopausal women with osteoporosis who are at high risk for fractures. Prolia is manufactured by Amgen Manufacturing Limited, a subsidiary of Amgen Inc.

Osteoporosis is a disease in which the bones become weak and are more likely to break. According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, 80 percent of the people in the US with osteoporosis are women. One out of every two women over age 50 will break a bone in their lifetime due to osteoporosis.

People with osteoporosis at high risk for fracture include those that have had an osteoporotic fracture, or have multiple risk factors for fracture; or those who have failed or are intolerant to other available osteoporosis therapy. Prolia works to decrease the destruction of bone and increase bone mass and strength. An injection of Prolia is recommended once every six months.

Prolia was approved with a risk evaluation and mitigation strategy (REMS) that includes a Medication Guide for patients and communications to health care providers that explains the risks and benefits of the drug. (Source: FDA Website, 1 June, 2010)

FDA Revises Recommendations for GlaxoSmithKline and Merck Rotavirus Vaccines

The FDA has revised its recommendations for rotavirus vaccines for the prevention of the gastrointestinal disease in infants and has determined that it is appropriate for clinicians and health care professionals to resume the use of Rotarix and to continue the use of RotaTeq. The vaccines are manufactured by GlaxoSmithKline and Merck, respectively.

In March, the FDA advised doctors to stop using Glaxo's vaccine after researchers found evidence of a porcine circovirus known as PCV1 in the vaccine. Those tests did not find the same pig virus in Merck's Rotateq, which has stayed on the market. However, more sensitive tests subsequently conducted on Rotateq found a low level of the same PCV1 virus, as well as a related porcine circovirus known as PCV2. Neither virus is known to cause illness in humans. 

The agency reached its current decision based on a careful evaluation of information from laboratory results from the manufacturers and the FDA's own laboratories, a thorough review of the scientific literature, and input from scientific and public health experts, including members of the FDA's Vaccines and Related Biological Products Advisory Committee that convened on May 7, 2010 to discuss these vaccines. The FDA also considered the following in its decision:

• Both vaccines have strong safety records, including clinical trials involving tens of thousands of patients as well as clinical experience with millions of vaccine recipients.
• The FDA has no evidence that PCV1 or PCV2 pose a safety risk in humans, and neither is known to cause infection or illness in humans.
• The benefits of the vaccines are substantial, and include prevention of death in some parts of the world and hospitalization for severe rotavirus disease in the US. These benefits outweigh the risk, which is theoretical. (Source: FDA Website, 5 May, 2010; and Jennifer Corbett Dooren, The Wall Street Journal, 8-9 May, 2010)  

FDA Approves Sanofi-Aventis' Treatment for Advanced Prostate Cancer

The FDA has approved Sanofi-Aventis' Jevtana (cabazitaxel), a chemotherapy drug used in combination with the steroid prednisone to treat men with prostate cancer. Jevtana is the first treatment for advanced, hormone-refractory, prostate cancer that has worsened during or after treatment with docetaxel, a commonly used drug for advanced prostate cancer.

In prostate cancer, the male sex hormone testosterone can cause prostate tumors to grow. Drugs, surgery, or other hormones are used to reduce testosterone production or to block it. Some men have hormone refractory prostate cancer, meaning the prostate cancer cells continue to grow, despite testosterone suppression. Different treatments are needed for men with this type of cancer.

Jevtana was reviewed under the FDA's priority review program, which provides for an expedited six-month review for drugs that may offer major advances in treatment, or provide a treatment when no adequate therapy exists.

Prostate cancer, which usually occurs in older men, is the second most common cancer among men in the United States, behind skin cancer. In 2006, the most recent year for which numbers were available, 203,415 men developed prostate cancer and 28,372 men died from the disease, according to the Centers for Disease Control and Prevention. (Source: FDA Website, 17 June, 2010)

FDA Approves New Indication for Novartis' Tasigna

The FDA has approved a new indication for Novartis' Tasigna (nilotinib) for the treatment of a rare blood cancer when it is first diagnosed. The cancer, called Philadelphia chromosome positive chronic phase chronic myeloid leukemia (Ph+ CP-CML), is a slowly progressing blood and bone marrow disease linked to a genetic abnormality.

Tasigna is believed to work by blocking a signal that leads to leukemic cell development. The new indication expands the use of Tasigna to adult patients in earlier stages of the disease. The FDA originally approved Tasigna in October 2007 for the treatment of Ph+CP-CML in adult patients whose disease had progressed or who could not tolerate other therapies, including Gleevec (imatinib).

When Tasigna was originally approved in October 2007, the FDA identified that the therapy placed patients at risk of an abnormal heart rhythm called QT prolongation. In March 2010, the FDA approved a Risk Evaluation and Mitigation Strategy (REMS) for Tasigna to help patients and health care professionals to better understand this risk. The REMS includes an updated Medication Guide and a communication plan to help reduce medication errors involving drug-food interactions and incorrect dosing intervals.

In CML, too many blood stem cells develop into a type of white blood cell called granulocytes. These granulocytes are abnormal and do not become healthy white blood cells. These cells can build up in the blood and bone marrow so there is less room for healthy white blood cells, red blood cells, and platelets. When this happens, infection, anemia, or unexpected bleeding may occur.

The FDA granted Tasigna a priority review for Ph+ CP-CML. The agency completed the review in six months. The new indication for Tasigna was approved under the FDA's accelerated approval program, which allows FDA to approve a drug to treat serious diseases with an unmet medical need based on an endpoint thought to reasonably predict clinical benefit. The company is required to collect additional long term efficacy and safety information data confirming the drug's benefit. The accelerated approval program provides earlier patient access to promising new drugs while the confirmatory clinical trials are being conducted.

Other FDA-approved drugs to treat CML include Gleevec and Sprycel (dasatinib). Tasigna and Gleevec are marketed by Novartis Pharmaceuticals; Sprycel is marketed by Bristol-Myers Squibb. (Source: FDA Website, 17 June, 2010)

FDA Approves First Diagnostic Assay to detect both HIV Antigen and Antibodies

The FDA has approved the first assay to detect both antigen and antibodies to Human Immunodeficiency Virus (HIV). It is approved for use in the diagnosis of HIV-1/HIV-2 infection in adults including pregnant women and children as young as two years old.

Manufactured by Abbott Laboratories, the highly sensitive assay is intended to be used as an aid in the diagnosis of HIV-1/HIV-2 infection, including acute or primary HIV-1 infection. Since it actually detects the HIV-1 virus (specifically the p24 antigen) in addition to antibodies to HIV, the assay can be used to diagnose HIV infection prior to the emergence of antibodies. Most tests used today in the diagnostic setting detect HIV antibodies only. Although direct detection of the virus itself by nucleic acid testing is available, it is not widely used in diagnostic settings.

The Centers for Disease Control and Prevention report that approximately 18 million people in the United States are tested for HIV each year. Most recent CDC estimates are that there are about 56,000 new HIV infections in the United States each year. In addition, there are more than 1 million people living with HIV in the United States, according to CDC.

The assay is not intended to be used for routine screening of blood donors. However, it is approved as a donor screening assay for HIV-1/HIV-2 infection in urgent situations where licensed blood donor screening tests are unavailable or their use is impractical. (Source: FDA Website, 21 June, 2010)

Pfizer Voluntarily Withdraws Cancer Treatment Mylotarg from US Market

Pfizer has announced the voluntary withdrawal from the US market of the drug Mylotarg (gemtuzumab ozogamicin) for patients with acute myeloid leukemia (AML), a bone marrow cancer. The company took the action at the request of the FDA after results from a recent clinical trial raised new concerns about the product's safety and the drug failed to demonstrate clinical benefit to patients enrolled in trials.

Mylotarg was approved in May 2000 under the FDA's accelerated approval program. This program allows the agency to approve a drug to treat serious diseases with an unmet medical need based on a surrogate endpoint - a laboratory measurement or a physical sign used as a substitute for a clinically meaningful endpoint that directly measures how a patient feels, functions, or survives.

Under accelerated approval, the company is required to conduct additional clinical trials after approval to confirm the drug's benefit. If those trials fail to confirm clinical benefit to patients, or if the company does not pursue the required confirmatory trials with due diligence, the FDA can withdraw the drug from the market using expedited procedures.

Mylotarg was approved to treat patients ages 60 years and older with recurrent AML who were not considered candidates for other chemotherapy. The initial approval was based on the surrogate endpoint of response rate (i.e., the percentage of patients whose leukemia decreased or disappeared in laboratory tests), observed in 142 patients with AML across three clinical trials.

A confirmatory, post approval clinical trial was begun by Wyeth (now Pfizer) in 2004. The trial was designed to determine whether adding Mylotarg to standard chemotherapy demonstrated an improvement in clinical benefit (survival time) to AML patients. The trial was stopped early when no improvement in clinical benefit was observed, and after a greater number of deaths occurred in the group of patients who received Mylotarg compared with those receiving chemotherapy alone.

At initial approval, Mylotarg was associated with a serious liver condition called veno-occlusive disease, which can be fatal. This rate has increased in the postmarket setting.

As a result of the withdrawal, Mylotarg will not be commercially available to new patients. Patients who are currently receiving the drug may complete their therapy following consultation with their health care professional. Health care professionals should inform all patients receiving Mylotarg of the product's potential safety risks.

Following the withdrawal, any future use of Mylotarg in the United States will require submission of an investigational new drug application to FDA. (Source: FDA Website, 21 June, 2010)

FDA Pushes Orphan Drug Research

Roche Holding AG, Johnson & Johnson, and Biogen Idec are being urged by US regulators to see whether existing medicines may help neglected disorders, after an incentive program failed to spark research on new therapies.

The FDA has published a list yesterday of 235 treatments that may have benefit in rare disorders and already have marketing clearance for other uses. Identifying "low-hanging fruit" may compel large drug makers to look beyond common ailments with guaranteed consumer demand, said Tim Cote, head of the agency's Office of Orphan Product Development. The list includes Roche's hepatitis drug Pegasys, J&J's leukemia medicine Leustatin, and Biogen Idec's multiple sclerosis drug Avonex.

About 30 million Americans have one of 7,000 rare diseases, defined by the FDA as conditions affecting fewer than 200,000 people in the US. Medicines developed to treat these conditions are called orphan drugs, under rules that encourage their development.

Roche's Pegasys has orphan status for chronic myelogenous leukemia. Roche is no longer studying Pegasys in cancer, said a spokeswoman for the company's Genentech unit.

Leustatin, made by J&J, is approved for hairy cell leukemia but has had orphan drug designation since 1990 for chronic lymphochytic leukemia and acute myeloid leukemia. J&J decided not to further develop Leustatin in part because there are other drugs available for leukemia, Ernie Knewitz, a spokesman, said. J&J is studying products for other types of neglected diseases, he said.

Also on the list is Biogen Idec's top-selling MS drug Avonex, which has had orphan designation since 1991 as a treatment for cutaneous t-cell lymphoma. While Biogen Idec initially pursued Avonex in "several indications," it now has no plans to develop it for cutaneous t-cell lymphoma, said Kate Weiss, a company spokeswoman. (Source: Catherine Larkin, The Boston Globe, 19 June, 2010)

IRS Accepting Applications for Qualifying Therapeutic Discovery Project

The IRS has announced that small firms may now begin applying for certification for tax credits or grants available under the Qualifying Therapeutic Discovery Project Program, created by the Affordable Care Act. These credits or grants are available for projects that show significant potential to produce new cost-saving therapies, create US jobs and increase US competitiveness.

Form 8942, Application for Certification of Qualified Investments Eligible for Credits and Grants Under the Qualifying Therapeutic Discovery Project Program, and its instructions are now available. Companies may submit applications for certification beginning immediately. Applications must be postmarked no later than July 21, 2010.

The Qualifying Therapeutic Discovery Project Program is targeted to projects that show potential to produce new therapies, reduce long-term health care costs, or significantly advance the goal of curing cancer within the next 30 years. The credit or grant covers up to 50 percent of the cost of qualifying biomedical research, up to a maximum credit of $5 million per firm and $1 billion overall, and is only available to firms with no more than 250 employees. Credits and grants are available for investments made in 2009 and 2010.

As part of the review process for research projects, the Department of Health and Human Services (HHS) will evaluate each project for its potential to produce new therapies, reduce long-term health care costs or cure cancer within 30 years. Only projects that show a reasonable potential to meet these goals will be certified as eligible for the credit or grant. The IRS will issue certifications by the end of October, based on the determinations made by HHS. More information on this program, can be found at http://grants.nih.gov/grants/funding/QTDP_PIM/index.htm. (Source: IRS Website, 18 June, 2010)