DID - May 19, 2008 Issue

Vol. 7 No. 98

Extra $275 Million for FDA Delayed By Lawmakers’ Fight Over War Funding

The Senate Appropriations Committee passed an amendment last week granting the FDA an immediate $275 million infusion, a sum FDA Commissioner Andrew von Eschenbach recently told a senior Republican lawmaker was necessary.

The amendment stipulates that $48.5 million be used for CDER operations and related field activities of the Office of Regulatory Affairs (ORA); $23.5 million for CBER and related ORA activities; and $21.8 million for the FDA Office of the Commissioner, Office of Operations, Office of Scientific and Medical Programs, Office of International and Special Programs and Office of Policy, Planning and Preparedness. The remainder is to be used for the Center for Food Safety and Applied Nutrition and other activities.

The amendment makes the $275 million available through the end of fiscal 2009 and stipulates that $100 million must be used for drug, device and biologic safety activities, $40 million for modernizing the agency’s science and workforce, $10 million for capital spending on laboratory facilities outside the Washington, D.C., area and $125 million for food protection.

How the FDA May Use the Money

In addition, von Eschenbach detailed ways the money could be used in his May 5 response to a request by Sen. Arlen Specter (R-Pa.), ranking member of the Senate Appropriations Subcommittee on Labor. In addition to amounts to be used for food safety or specifically for medical devices, he identified the following potential uses:

  • $27 million to support advanced manufacturing technologies, nanotechnology and cell and gene therapies;
  • $17 million for, among other activities, pediatric drugs, postmarket studies, clinical trials, active drug surveillance, labeling and safe use of drugs;
  • $15 million to develop and use a regulated product information data warehouse to share intelligence with other regulators;
  • $15 million to increase data access and analysis and develop scientific methods of data mining for adverse event signals;
  • $10.2 million for 575 more domestic medical product inspections;
  • $7.8 million to increase the agency’s presence in three of five geographic regions outside the U.S.;
  • $7.5 million to improve lab infrastructure for rapid analysis of product content;
  • $6.6 million to increase import exams and sampling/lab analyses;
  • $5.4 million for 120 more foreign medical product facility inspections, which would include facilities for drugs, devices, biologics and veterinary medicine;
  • $5 million to strengthen emerging science programs in the centers and the National Center for Toxicological Research;
  • $4 million to expand science training and professional development;
  • $4 million to launch a Science Fellows Program and start recruiting its first 500 fellows; and
  • $3 million for IT systems to achieve an integrated inventory database.

The FDA told DID that, if authorized, the funding needs in von Eschenbach’s assessment would not all be spent during fiscal 2008 and would enable the agency to implement HHS’ Import Safety Action Plan.

“These resources will also allow FDA to strengthen its information technology to improve threat assessment, conduct product safety research and analysis, detect product safety and integrity problems and allow more effective targeting of FDA inspection teams,” the FDA told DID.

When Will the Money Be Available?

The FDA’s money is in one of three amendments passed by the Senate committee, which has sent them to Senate leaders who may introduce them as legislation this week. The other two amendments involve policy and funding for the war in Iraq.

The House has voted on its versions of the three amendments, approving the one with funding for the FDA. But it did not approve one of the two remaining amendments related to the Iraq war. Senate and House staff were not able to provide bill or resolution numbers for the amendments and are uncertain what the next step for the amendments may be as Democrats and Republicans spar over increased funding for the war.

Von Eschenbach’s letter, which contains nine pages of detail, can be accessed at www.fdanews.com/ext/files/Drug_Industry_Daily/vonEschenbachSpector.pdf. — Christopher Hollis, Martin Gidron, David Grant


Theft Prompts J&J Recall

After learning that a transport trailer carrying 9,000 vials of high-value injectable medications was stolen while in transit in Tennessee, Johnson & Johnson (J&J) is recalling several lots of the drugs associated with the shipment.

“To ensure patient safety, Centocor and Ortho Biotech are voluntarily withdrawing products with lot numbers matching those of the stolen product,” the J&J subsidiaries said. The affected medications include three lots of erythropoiesis-stimulating agent Procrit (epoetin alfa), two lots of cancer treatment Doxil (doxorubicin HCl) and two lots of TNF inhibitor Remicade (infliximab).

J&J told DID the recall is not expected to affect the availability of the drugs.

“The transport trailer and product have not yet been recovered,” J&J said. “If the stolen product were to be reintroduced into distribution channels, the companies cannot guarantee that products were stored at appropriate temperatures, nor can the companies guarantee the products were not damaged.”

The theft occurred May 6 when the driver took a break at a truck stop. The shipment originated from a J&J distribution center in Kentucky operated by JOM Pharmaceutical Services, a J&J subsidiary.

The firm discontinued shipping drugs with lot numbers matching the stolen medicines the next day. Healthcare providers that received the products before the theft should consider them safe for use.

Mike Smithers, lead investigator on the case and a police detective in Louisville, Ky., told DID the perpetrators are suspected of following the transport trailer from the distribution center to the truck stop. He said there has been a rash of transport thefts for all types of goods in the area since UPS opened a distribution center in the region. — Christopher Hollis


MedWatch Report Warns of Birth Defects With CellCept, Myfortic

The FDA is again warning physicians that CellCept and Myfortic are linked to increased risks of early abortion and birth defects and that it is aware that CellCept is being prescribed for off-label conditions.

In Friday’s MedWatch and notice to healthcare professionals, the FDA cited reports of infants born with serious congenital anomalies, including microtia and cleft lip and palate, following exposure to mycophenolate mofetil (MMF).

MMF, the active drug substance in CellCept, is an ester of the active metabolite mycophenolic acid, the active drug substance in Myfortic.

Roche’s CellCept and Novartis’ Myfortic are approved to prevent organ transplant rejection. In most adverse event cases, the mothers were taking MMF following a transplant. However, some were being treated for immune-mediated conditions for which CellCept is not approved. Treatment began before their pregnancies and continued into the first trimester or until the pregnancy was detected.
The FDA said it is continuing to work with Roche and Novartis on reducing the risk of fetal exposure.

The FDA revised the labeling for both CellCept and Myfortic last November, adding information on the risk of spontaneous abortion and birth defects to the boxed warning. The agency also issued MedWatch Alerts for both transplant drugs last year.

Earlier this year, the FDA said it was investigating the possibility that the drugs contribute to a rare disorder affecting the central nervous system (DID, April 11).

Last November, Roche gave the FDA an evaluation of cases of progressive multifocal leukoencephalopathy (PML) in patients who received CellCept in addition to other immunosuppressive drugs. The company also submitted recommendations to revise the drug’s prescribing information for PML. The FDA asked Novartis for similar recommendations.

PML usually occurs in patients with immune systems suppressed by disease or medicines. PML patients frequently die, and survivors can develop permanent disabilities due to irreversible nerve damage.

The agency estimated it would take approximately two months to complete the review of postmarketing reports and the proposed revised prescribing information.
According to the NIH, Salix’s Azasan, GlaxoSmithKline’s Imuran and different generic drugs with the same active ingredient — azathioprine — are alternatives to CellCept and Myfortic. Azathioprine’s labeling warns of the risk of developing certain types of cancer, including skin cancer and lymphoma.

Roche and Novartis did not respond to requests for comment by press time. — April Astor


Immunize All Patients 60 and Older Against Shingles, CDC Says

People age 60 and older should get the zoster (shingles) vaccine unless they have specific contraindications, according to the Centers for Disease Control and Prevention (CDC).

The recommendation was released in advance of a formal publication date by the Advisory Committee on Immunization Practices (ACIP). It applies to Merck’s Zostavax (zoster vaccine, live), which the FDA approved in May 2006.

The Merck product is a live attenuated vaccine for the prevention of herpes zoster (shingles) and its complications. Zoster is a localized, generally painful cutaneous eruption that occurs most frequently among older adults and immunocompromised people. It is caused by reactivation of latent varicella zoster virus decades after an initial chickenpox infection.

Approximately one in three people develop zoster during their lifetime, resulting in an estimated 1 million episodes in the U.S. each year, ACIP noted. A common complication of shingles is postherpetic neuralgia (PHN), which occurs in 10 percent to 18 percent of patients and causes chronic, often debilitating pain that can last months or years.

In a large clinical trial, the zoster vaccine was partially effective at preventing zoster, reducing the severity and duration of pain, and preventing PHN among those who did develop the disease.

In the 60-plus age group, the zoster vaccine can be given to people who have had a previous episode of zoster or chronic medical conditions, such as chronic renal failure, diabetes mellitus, rheumatoid arthritis and chronic pulmonary disease.

Healthcare providers are advised to offer the vaccine at the patient’s first visit. It is not necessary to ask patients about their history of chickenpox or to do serologic testing for varicella immunity.

The vaccine is administered as a single 0.65-mL dose subcutaneously in the deltoid region of the arm with no booster shot. It is not indicated to treat acute zoster, prevent patients with acute zoster from developing PHN or to treat ongoing PHN.

The ACIP document can be viewed at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr57e0515a1.htm. — Martin Gidron


Generic Viramune Gets Nod Under PEPFAR Program

The FDA has granted tentative approval for Matrix Laboratories’ generic version of Boehringer Ingelheim’s 200-mg Viramune tablets, a non-nucleoside reverse transcriptase inhibitor (NNRTI) for use in combination with other antiretrovirals for the treatment of HIV. 

The generic Viramune (nevirapine) application was considered under the expedited review provisions of the President’s Emergency Plan for AIDS Relief (PEPFAR), a five-year, $15 billion program aimed at combating HIV and other disease in 114 countries — including 15 focus countries primarily in Africa — that President Bush announced in 2003. 

Tentative approval means the FDA has concluded that a drug product has met all required standards but is not eligible for marketing in the U.S. because of existing patents or exclusivity rights. The product is eligible for consideration for purchase outside the U.S. under the PEPFAR program, the agency said.

India-based Matrix received FDA approval for its generic version of GlaxoSmithKline’s 300-mg Retrovir (zidovudine) tablets, another NNRTI used in combination with other antiviral drugs to treat HIV, in February.

Because GSK’s patents on Retrovir have expired, Matrix’s generic product can be sold in the U.S. as well as be purchased under PEPFAR (DID, Feb. 18). — Elizabeth Jones


Sanofi’s Second Shot at Dronedarone Looking Good

Sanofi-aventis plans to resubmit its NDA for its atrial fibrillation treatment Multaq following positive clinical data for the previously not-approvable drug. The company says it also expects to submit a registration dossier to the European Medicines Agency.

In 2006, the FDA issued a not-approvable letter for Multaq (dronedarone), and sanofi said it would resubmit its application in the first part of 2008 after completion of a new trial (DID, Sept. 1, 2006). That trial, ATHENA, shows the drug decreased patients’ risk of cardiovascular hospitalizations or death from any cause by 24 percent, according to the company.

In the ATHENA trial, Multaq showed a 30 percent decrease in the risk of cardiovascular death on top of standard therapy, including rate control and anti-thrombotic drugs, in patients with atrial fibrillation or atrial flutter, the company said.

Multaq also significantly decreased the risk for death from arrhythmia by 45 percent, and there were fewer deaths from any cause in the dronedarone group compared with placebo, according to the company. First cardiovascular hospitalization was reduced by 25 percent in the dronedarone group.

ATHENA was a double-blind, randomized study in patients with atrial fibrillation. It is the first morbidity-mortality study as part of the Multaq Phase III clinical development program, sanofi said. — April Astor

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Reporters: Martin Gidron, April Astor, Christopher Hollis, Elizabeth Jones

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