Pradaxa, Gilenya, Other Problem Drugs Approved Too Fast: Report

Some experts are criticizing the FDA for expediting the approval of certain drugs, like the blood thinner Pradaxa and the multiple sclerosis drug Gilenya, before they were properly vetted. 

U.S. consumers may have been exposed to dangerous drugs in the name of fostering innovation, according to an editorial by Thomas J. Moore and Dr. Curt D. Furberg that was published in the September 5 edition of the Journal of the American Medical Association (JAMA).

Through a program known as the “Expedited Drug Development Pathway,” the FDA has allowed drug-makers to fast-track drugs that looked promising, but many have later been found to have questionable benefits and sometimes deadly side effects, the editorial states.

“Although enabling new drugs with a favorable benefit-to-harm balance to become available to patients more rapidly is a laudable goal, the underlying question is what public health risks are taken when drugs are approved for widespread use while important safety questions remain unanswered,” the editorial states.

The authors point out that in 2011 the FDA approved 16 of the 35 new drugs placed on the market through an expedited process; meaning nearly half (46%) of all such medications may not have been thoroughly tested and reviewed to ensure that they were safe and effective before consumers were given the drugs.

Pradaxa Fast-Tracked Without Reversal Agent

One fast-tracked drug highlighted in the report is the controversial new blood thinner Pradaxa, which has been linked to hundreds of deaths and thousands of adverse event reports where consumers suffered uncontrollable bleeding that doctors were unable to stop due to the lack of a reversal agent.

Pradaxa (dabigitran) is an anticoagulant that was introduced by Boehringer Ingelheim in October 2010 for prevention of strokes in patients with atrial fibrillation.  The medication has been aggressively promoted as a superior alternative to warfarin, because it is easier to take and requires less monitoring.  However, if bleeding problems develop on warfarin, patients can be given a reversal agent to quickly stop the bleeding. No such antidote is available to stop Pradaxa bleeding.

Dozens of Pradaxa lawsuits have now been filed against the Boehringer Ingelheim, alleging that the drug maker failed to provide adequate warnings to consumers and the medical community about the risk of bleeding and the lack of a reversal agent to stop the blood thinning effects.

After the medication was allowed to reach the market in October 2010 under this expedited process, Pradaxa quickly became one of the medications most commonly linked to adverse event reports submitted to the FDA.

According to a report issued earlier this year by the Institute for Safe Medication Practices (ISMP), which analyzed all adverse event reports submitted to the FDA during 2011, there were 2,367 reports of Pradaxa bleeding problems, as well as 542 reports of death among Pradaxa users. By comparison, warfarin was linked to 1,106 adverse event reports, including 72 patient deaths.

Gilenya Heart Problems Showed Up After Market Approval

Another example given by the authors was the multiple sclerosis (MS) drug Gilenya, which was approved by the FDA in 2010. The editorial points out that there were seven major safety issues during clinical trials, including heart problems, liver toxicity, increased risk of infection, reduced pulmonary function, teratogenicity, macular edema and potentially an increased risk of cancer. Clinical trials of doses of 5 mg and 2.5 mg were halted due to safety reasons, forcing the FDA to go with the lowest dose possible of 0.5 mg.

Gilenya (fingolimod) was approved by the FDA in 2010 as an oral treatment for relapsing forms of MS in adults. It is used to reduce how often flare-ups occur and to delay the onset of physical disability caused by MS.

Despite concerns over the safety of Gilenya when it was reviewed, the FDA agreed to fast-track the drug’s approval with minimal testing under a program aimed at getting crucial drugs to the market to address medication needs that have not been met by other drugs. It is the only oral MS drug on the market.

In May, the FDA added new Gilenya warnings about the risk of heart problems after a patient died within 24 hours of taking the drug.

The editorial also pointed out the thyroid cancer drug Caprelsa (vandetanib) was approved after only a single trial of 331 patients with thyroid cancer. The toxicity of the drug has been found to be so high that the survival rate for patients taking it is not much different than if they were given a placebo, the report states. There is so little clinical data that the FDA doesn’t know if lowering the dose will help.