Thursday, September 23, 2010

FDA Restricts Use of Diabetes Drug Avandia

FDA Decides Not to Ban Avandia, but Puts Restrictions on How It’s Used.
By Daniel J. DeNoon
WebMD Health News

Sept. 23, 2010 -- The FDA will not ban Avandia -- but stringent restrictions will make it far harder for doctors to prescribe the safety-troubled diabetes drug.

The European Medicines Agency took harsher action. European sales of Avandia-containing drugs will be suspended over the next few months, although the agency did not formally withdraw approval.

The 600,000 U.S. patients currently taking Avandia can continue to take the drug only if their doctors officially attest that their patients understand the risks, that the drug is helping them, and that no other diabetes drug can keep their blood sugar under control.

New Avandia prescriptions can only be written for patients who, for medical reasons, cannot take Actos. Actos, a diabetes medication in the same class as Avandia, does not cause the heart problems linked to Avandia.

"Avandia will be available to new patients only if they cannot achieve [blood sugar] control on other agents and cannot take Actos," FDA commissioner Margaret A. Hamburg, MD, said at a news conference. "Current patients can continue taking Avandia only if they benefit and understand the risks."

Avandia maker GlaxoSmithKline will be required to establish a Risk Evaluation and Mitigation Strategy (REMS) program. Patients, their doctors, and their pharmacists will have to enroll in the program in order to receive, prescribe, or sell Avandia.

Avandia Heart Risks Clouded by Uncertainty

Hamburg admitted that FDA experts are split over how to interpret the scientific evidence suggesting that Avandia damages the heart. Both Avandia and Actos increase the risk of heart failure. But evidence suggests that only Avandia increases risk of heart attack.

Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research, noted that an FDA advisory panel last July split over the issue of whether the evidence proved Avandia unsafe.

"In and outside the agency there is mostly agreement on the facts, but not on the weight of the safety analysis," Woodcock said at the news conference. "This has resulted in different conclusions, not only inside FDA but among outside experts. This reflects uncertainty in the science that tells us whether or not Avandia causes these problems."

Questions about Avandia heart safety should have been answered by the RECORD study, which Avandia maker GlaxoSmithKline conducted at the behest of the European drug agency. This study found Avandia to be safe, but critics have lambasted the study's poor design. Moreover, an FDA analysis suggests that the study failed to investigate all possible heart attacks in study patients.

Today's FDA action will require GlaxoSmithKline to convene a panel of independent scientists to review the RECORD data. That review may cause the FDA to lift the new Avandia restrictions -- or to ban the drug.

The FDA today also officially ended a study called TIDE, which was directly comparing Avandia and Actos. The FDA decided that the study, which already had been suspended, posed too much risk to participants.

In a statement, GlaxoSmithKline says it "continues to believe that Avandia is an important treatment for patients with type 2 diabetes," but that it will work with the FDA and the European Medicines Agency to implement their decisions.

Thank you, WebMD

Wednesday, September 22, 2010

Gilenya, First Oral MS Drug, Gets FDA Nod

Once-Daily Capsules Cut MS Relapses, Delay Progression
 
By Daniel J. DeNoon
WebMD Health News
 
Sept. 22, 2010 -- The FDA today approved Novartis' Gilenya, the first oral drug for multiple sclerosis (MS). Gilenya (formerly spelled Gilenia, generic name fingolimod) last June received the overwhelming approval of an FDA expert advisory panel.

Gilenya treats the relapsing form of MS. The drug significantly reduces MS attacks. However, it has serious side effects, with possible heart, lung, and eye toxicity and increased risk of infection. Patients must be closely monitored, and regular eye exams are advised.

In MS, white blood cells attack the myelin sheaths that protect nerve cells. Gilenya, the first drug in its class, keeps white blood cells penned up in lymph nodes by taking away the chemical key they need to unlock the lymph node door.

Fewer white blood cells mean fewer MS attacks. But it also means less protection against infections. Novartis will set up a careful program for educating and monitoring patients taking the drug. Moreover, the company will continue long-term studies to look for side effects that may occur with longer-term use.

Gilenya was invented as a new way to prevent rejection in kidney transplant patients. But at the necessary dosage, the drug was far too toxic. The dose that would be used to treat MS is five times lower than the lowest dose tested in the transplant studies.

Even at this dosage, Gilenya can have severe toxicity. In clinical trials, side effects linked to Gilenya included:

    * Elevated liver enzymes
    * Macular edema (swelling of the central portion of the retina, causing distorted vision)
    * Elevated blood pressure
    * Shortness of breath
    * Bronchitis
    * Diarrhea
    * Bradycardia (slowing of the heartbeat, seen only upon first treatment. The FDA panel recommended that patients be required to receive their first dose under medical supervision).

Two fatal herpes infections occurred in MS patients treated with Gilenya at 2.5 times the 0.5-milligram dose for which Novartis is seeking approval.

But overall, the drug's benefits outweighed its risks among the more than 2,600 MS patients who took the drug in clinical trials.