AMPLIGEN NOT APPROVED BY FDA
Experimental drug for ME Rejected
From Co-Cure:21 Dec 2012 Posted by Heidi LedfordA 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.
From The Wall Street Journal -20/12/2012
By Jennifer Corbett Dooren A federal advisory panel on Thursday said a proposed medicine from Hemispherx Biopharma Inc. HEB -5.26% to treat chronic fatigue syndrome isn't ready for approval, dealing another setback to the drug maker.
Hemispherx Biopharma is seeking approval from the U.S. Food and Drug Administration for the drug, Ampligen. The product, which been in development for more than two decades, was reviewed Thursday by the agency's arthritis-drugs advisory panel, which is made up of non-FDA medical experts.
In an 8-to-5 vote, the panel said the company didn't provide sufficient data to support the approval of Ampligen.
The vote amounts to a recommendation that FDA not approve the drug. Several panel members said they struggled with their decisions because it appears the drug works in certain patients even if it wasn't strongly shown in the clinical data presented to the panel.
"I think the advisory panel in general hopes there will be an effective drug and hopes this might be the drug" for chronic fatigue syndrome, said Lenore Buckley, the panel's chairwoman and a professor at Yale School of Medicine. "We are interested in seeing more data."
A decision by the FDA on whether to approve Ampligen is expected by early February. Almost three dozen patients or family members testified in person or via video before panel, urging them to approve Ampligen.
Anita Kathryn Patton, who's had chronic fatigue syndrome for more than 20 years, was first given Ampligen in 1997. "It was like rising from the dead," Ms. Patton said of her disease improvement. She and some other patients are receiving Ampligen through a special access program at a cost of about $25,000 a year.
At issue is whether Ampligen, which is the drug's proposed brand name, is effective and safe. The FDA said there was missing data in clinical studies that made it hard to tell whether the drug is safe. Potential safety concerns include infections and liver problems. FDA medical reviewers questioned whether the data meet drug-approval requirements demonstrating "substantial evidence" of safety and efficacy, or effectiveness. Theresa Michele, an FDA team leader, said the agency believes that chronic fatigue syndrome is a serious disease that needs treatments, but said clinical studies submitted in support of products have to meet federal drug approval standards showing "substantial" safety and effectiveness. "We have to be certain a drug works and we clearly know what the risks are," Dr. Michele said.
The FDA and the company differed on whether one of the main clinical studies reached a goal showing a statistically significant test showing patients receiving the drug were able to walk on a treadmill for a longer period than patients receiving placebo injections. The company said on average there was an improvement of about one minute while the FDA said the difference appeared to be about 20 seconds. "Regardless of the [measurement] approach there's a consistent pattern of benefit in the data, which favor Ampligen," said William Carter, Hemispherx chief executive. At a minimum, Dr. Carter said, the drug "prevents further disease progression."
After the meeting, Dr. Carter said he had no comment.
Chronic fatigue syndrome, also known as myalgic encephalomyelitis, is believed to affect more than one million Americans, according to the Centers for Disease Control and Prevention. The condition is marked by severe fatigue, muscle pain and memory and concentration problems. It isn't known what causes the condition and there are currently no specific treatments. Ampligen, an injectable drug, is believed to boost the body's immune system and fight viruses.
Further Reading: http://www.medpageto...sorders/36569