FDA has recently taken second looks at weight-loss drugs from Vivus and Arena, and now it’s giving Hemispherx’s experimental chronic fatigue syndrome drug, Ampligen, a second chance with a Thursday advisory committee hearing.

The injectable has been kicking around the regulatory agency since 1988, when its Phase I tests were reviewed by the Center for Biologics Evaluation and Research. It’s since been looked at by other groups within the FDA, and the results share one theme: give us more information.

A November 21 memo to the Pulmonary, Allergy and Rheumatology advisory committee in November by clinical team leader Theresa Michele indicates that questions remain, despite a 2009 complete response letter in which the agency said Hemispherx’s supporting data was found lacking. Among the 2009 complaints: inadequate evidence of effectiveness or safety; inadequacy of drug-drug interaction studies; inadequate analytical methods and drug product specifications. The FDA requested at least one additional clinical trial. The 2009 letter echoed one issued in 2007 when the Cardio-Renal Drug Products group refused to accept Hemispherx review application over deficient data, including missing studies and inconsistent patient counts, among other reasons.

The drug changed committees in 2011, but the data Thursday’s committee will be reviewing is an analysis of the information Hemispherx submitted three years ago. Although the briefing documents are for reference and do not indicate judgment, the notes show the committee is cross-referencing past experiences with present ones.

Among the FDA’s notes:

  • Hemispherx did not conduct any dose ranging studies, but noted in the complete response that the minimal effective dose is 200mg twice a week.
  • FDA finds fault with the remix of the exercise tolerance data, which is meant to assess patient activity thresholds. The FDA notes indicate Hemispherx’s approach was flawed because it included a variable endpoint, among other reasons, including “there is no evidence suggesting that improvement with Ampligen is more likely in patients who may spontaneously improve.”

A Hemispherx spokesperson told MM&M the company couldn’t comment on the committee’s notes before Thursday’s review.

Chronic fatigue syndrome is associated with unexplained, persistent fatigue that lasts at least six months and can include impaired concentration as well as muscle and joint pain. Although a study published in the journal mBio in September indicated that two viruses thought to be associated with the condition were not found among the patients diagnosed with CFS, the condition is attractive for two key reasons: first, no pharmacological therapy currently exists. Second, Hemispherx locked in an Orphan Drug designation in 1993, when the number of diagnosed patients was well below the rare-disease threshold of under 200,000 patients. According to the FDA briefing documents, the CFS patient pool was around 18,000 people at the time. The current estimate has since jumped to around 1 million patients, but the FDA noted that the population at the time of designation is what matters, not how large the patient pool is when the drug comes up for review. The designation has the potential to be a lucrative one, because of an extended exclusivity period.