Last month's FDA workshop for chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME) – the first of its kind, one of 20 mandated by the Prescription Drug User Fee Act – hardly transformed the treatment landscape in the aftermath of the agency's refusal to approve the Toll-like receptor 3 modulator Ampligen (rintatolimod), the CFS therapy from Hemispherx Bioscience Inc.
But patients and their advocacy groups were given hope, and the FDA is taking comments from the public until August.
"The big news that came out of the second day [of the workshop] was the FDA's commitment to do a regulatory guidance document on ME CFS to help define what the issues are," said Kimberly McCleary, president and CEO of the Chronic Fatigue and Immune Dysfunction Syndrome Association of America, who took part in the workshop.
McCleary, in Washington this week at a federal CFS advisory committee meeting (not the same as an FDA adcom), noted that Jody Roth, director of regulatory affairs for Indianapolis-based Eli Lilly and Co., spoke during the final panel of the workshop, held April 25 and 26.
"After the FDA went on record with that intention to establish a guidance document, [Roth] said that is going to help bring a lot of people forward, because right now it's just too fuzzy," McCleary told BioWorld Today. "The symptoms are kind of all over the place, we don't have a target and the population is defined in so many different ways. Some of the dialogue at the meeting had been that when patients start to feel better, they do more, and that leads to a worsening of their symptoms. So even if the drug is helping, you have to find the right ways to measure it."
The guidance document will "define a roadmap, if you will," that could help companies not only establish endpoints, but also figure out "which end of the spectrum to go after," – i.e., severe CFS or disease that's just starting to manifest, McCleary said. "Maybe somebody will get Ampligen back on its feet, or repurpose treatments that are already out there for other indications, rituximab [Rituxan, Roche AG and Biogen Idec Inc.], for example."
Testimony at the workshop included remarks such as those delivered by CFS patient Mary Schweitzer. In 1994, she was a 44-year-old professor of history at Villanova University when she suffered the first of many blackouts, along with ataxia, short-term memory loss, dyslexia and massive confusion.
"I poured coffee into a silverware drawer convinced it was a cup," she told the workshop. By 1998, she was bedridden, and had been wrongly diagnosed a number of times, which led to various, ineffective medications. Then she was tested and found positive for 37kDa Rnase-L Factor, a predictor for success with the treatment of Ampligen.
After two months on the drug by way of a special program, she was walking. At five months, she could drive. Twenty months later, having significantly improved, she quit Ampligen, and then worsened. She started on the drug again. "It's that important that I remain on Ampligen," she said. "Without it, I would not be here talking to you. Without it, I don't have a life."
An FDA advisory panel voted 8-5 in December against recommending approval of Ampligen, based on safety and efficacy data. At the meeting, desperate CFS patients begged for the drug's marketing clearance, saying Ampligen had worked for them in trials, but committee members decided the studies were inadequately done, and did not show convincing enough effects to merit a positive outlook. (See BioWorld Today, Dec. 21, 2012.)
By a 9-4 margin, panelists opined that there was not substantial evidence of efficacy, and voted similarly on the question of whether safety had been thoroughly assessed and characterized. The safety profile, considered by itself, suggested approval for the drug was merited, the committee decided by an 8-5 ballot, but that was not sufficient to save Ampligen.
Shortly thereafter, the other shoe dropped, in the form of a complete response letter (CRL). CFS patient Robert Miller, who also spoke at the workshop, embarked on a hunger strike intended to draw attention to the plight of himself and his peers, which gained notice from regulators and politicians, but did not do anything to put Ampligen – or any other therapy for CFS, once considered a bogus disease – on the market. (See BioWorld Today, Feb. 6, 2013.)
Since then, CFS activists have called for such potential solutions as a development partnership with the National Institutes of Health, or a larger, more-experienced firm than Philadelphia-based Hemispherx. So far, nothing. Ampligen's rocky road to its latest defeat included a CRL in 2009 that came after Hemispherx had been working on the compound for a decade. (See BioWorld Today, Dec. 3, 2009.)
The workshop provided no explicit hope for Ampligen. "The FDA was pretty careful at the outset to say that this is not a product-specific meeting," McCleary said. "[Regulators said] we can talk about the different products that are used, not here to focus on one particular product."
Talk of Ampligen "came from patient testimony," she said. "Bob Miller and others were there to sort of bring that point forward, but it wasn't part of the construct of the meeting. There wasn't a speaker on that topic."