Pradaxa, an anti-coagulant drug marketed by Boehringer Ingelheim Pharmaceuticals, enjoyed an unusually smooth (and quick) ride towards FDA approval.  Rather than spending months pouring over clinical studies and safety data, FDA employees instead approved Pradaxa based primarily on a single study and did so in just six months.  Below are some highlights from the drug’s unprecedented fast-tracking by the FDA:

  • December 15, 2009 – Original New Drug Application (NDA) filed by Boehringer Ingelheim with the FDA seeking approval of Pradaxa (dabigatran exteliate), a direct thrombin inhibitor, for the prevention of strokes in patients with atrial fibrillation not caused by valvular heart disease.
  •  February 12, 2010 – FDA issues a Refusal to File Letter due to data integrity issues in the RE-LY trial, the primary data utilized by Boehringer Ingelheim to substantiate its claims of Pradaxa’s superiority over Coumadin (also known as warfarin) for the prevention of strokes in patients with atrial fibrillation.
  •  April 19, 2010 – Boehringer Ingelheim resubmitted its New Drug Application for Pradaxa along with a Medication Guide which is supposed to provide important drug-related safety information directly to patients.
  •  August 24, 2010 – The New Drug Application for Pradaxa was amended to include a REMS strategy.  The FDA Amendments Act of 2007 gave the Agency the authority to require a Risk Evaluation and Mitigation Strategy (REMS) in hopes of improving drug safety, the adequacy of warnings given to patients, and ensuring that the claimed benefits for risky medications are well substantiated.   A REMS program can include production of a medication guide, a communications plan, or other safeguards intended to protect patients.  The FDA ruled, inexplicably, that a communications plan was not required in connection with the approval of Pradaxa.
  •  September 20, 2010 – The Cardiovascular and Renal Drugs Advisory Committee to the Food & Drug Administration conducted a hearing regarding approval of Pradaxa for sale in the United States.  The panel voted unanimously in support of approval of the drug for use in stroke prevention in patients with atrial fibrillation.
  •  October 19, 2010Pradaxa was approved for sale and marketing in the United States by the FDA after only six months of review by the Agency.

The FDA has several timetables that it follows for approval of New Drug Applications (which has cut the average time period for drug approvals from 27.2 months to 13.8 between 1993 and 2003):

  • Fast Track – 60-day review process for drugs that treat serious disease and fill an unmet medical need or show some advantage over other available treatments (such as greater efficacy, fewer side effects, or improve the ability to diagnose a disease);
  •  Accelerated Approval  – permits the Agency to approve drugs based upon surrogate endpoints (essentially looking only for signs that a drug may cure a disease) rather than clinical outcomes (actually proof that it does cure the disease); and
  •  Priority Review – allows drug manufacturers to be placed ahead of other pending applicants if their new drug would provide a major advance in treatment for a particular condition or a completely new treatment option.

The emerging litigation over Pradaxa will be focusing closely on this approval process and whether short-cuts were taken as well as whether the FDA was provided accurate and complete information about the special risks that patients taking Pradaxa are facing and whether those risks are truly outweighed by the claimed benefits of the drug. Discovery in these individual lawsuits brought on behalf of patients who have suffered catastrophic or fatal bleeding episodes as a result of their use of Pradaxa will seek to answer a number of fundamental questions:

  • Did Boehringer Ingelheim deserve an expedited approval of Pradaxa?
  • Was approval of the drug even appropriate in light of other pending drug applications for medications that have the same benefits as Pradaxa but also have an available reversal agent or antidote, one of the critical defects in Pradaxa?
  • What factors led to the unanimous decision by the Advisory Committee? Were those committee members biased? Did they have financial ties to Boehringer Ingelheim?
  • Does Pradaxa meet an unfilled need in the medical community?
  • Does Pradaxa provide a greater benefit over warfarin, a drug whose safety profile has been documented and understood for more than 50 years?

It will likely be several years before the litigation process answers these questions, and far too late to make a difference for the thousands of patients who have already suffered harm.