A drug for chronic fatigue syndrome that spent decades in clinical development and won fervent patient support has been turned down for approval by a committee of advisers to the US Food and Drug Administration (FDA) who voted 9–4 against it. The drug, named Ampligen (rintatolimod), has not been shown to be effective or safe, the committee determined on 20 December.

Ampligen is a double-stranded RNA molecule (called poly I:poly C) which is thought to stimulate the immune system. The FDA does not have to follow the recommendations of its advisers, but briefing documents released by the agency strongly suggest that it will. The FDA’s list of deficiencies in the drug application submitted by Hemispherx Biopharma is stunning and encompasses nearly every aspect of clinical testing.

“Key deficiencies included inadequate evidence of effectiveness or safety, inadequacy of drug–drug interaction studies, lack of carcinogenicity assessment, lack of anti-drug antibody determination, and inadequate analytical methods and drug product specifications,” the agency wrote in one of several sections listing problems associated with the application.

FDA representatives also expressed concern over inconsistencies in the data and statistical analyses. An agency representative says of the data: “It raises our eyebrows and makes us wonder what else is in the database that we’re not seeing.”

Despite these weighty caveats and the drug’s middling performance in the clinic when averaged across all patients, several people with chronic fatigue syndrome (CFS; also called myalgic encephalomyelitis) testified that Ampligen yielded dramatic improvements in their symptoms. Some moved to Reno, Nevada, to be near the clinical-testing site and to receive infusions of the drug.

Alaine Perry, who served as a patient representative on the advisory committee, acknowledged that the Ampligen data are slim, but noted that CFS symptoms can be so severe that some patients would willingly take on a significant mortality risk for the promise of even minor relief of their symptoms. “A very small improvement in a disease like this is life altering,” she said. There are no other approved treatments specifically for CFS.

Accelerated approvals are sometimes used in cases of serious unmet medical need, and there was speculation ahead of Thursday’s meeting that recent legislation charging the FDA with expanding its use of accelerated approvals may come to bear on Hemispherx’s application. Ultimately, however, the FDA is bound by requirements that drug-makers convincingly demonstrate efficacy before approval, representatives said. In fact, according to the FDA briefing documents, the agency made it clear to Hemispherx in June that its application would be unlikely to win approval without additional clinical trials. That revelation probably came as a surprise to many Hemispherx investors, noted The Street’s Adam Feuerstein.