“The Alzheimer’s Plan”: CFS/ME Patients Seek “Loosening” Of Approval Requirements

FDA’s recent guidance on drug development in early-stage Alzheimer’s did not change the standard of evidence required for approval, agency official says amid calls to ease requirements for chronic fatigue syndrome/myalgic encephalomyelitis.

FDA’s efforts to aid drug development in Alzheimer’s disease have prompted calls among some patients with chronic fatigue syndrome/myalgic encephalomyelitis that they, too, should be able to benefit from what they say are “looser” drug approval standards.

During FDA’s April 25-26 CFS/ME workshop and in comments submitted to the public docket, patients have urged the agency to ease the approval requirements for new drugs as it has done for Alzheimer’s through a February draft guidance.

That guidance lays out a pathway for testing and approval of drugs in patients with early-stage disease, the target population thought to offer the best chance for affecting the course of the disease but a difficult one to study because patients may have little to no functional or cognitive impairment.

The guidance would allow a single primary outcome measure that combines cognition and function in patients in the early stage of the disease to serve as the basis for drug approval. It also opens the door to accelerated approval based upon showing a drug’s intermediate effect on a valid and reliable cognitive assessment that is used as a single primary outcome measure (Also see "Guidance For Drugs To Target Early Alzheimer’s Notes Lack Of Metrics, Biomarkers" - Pink Sheet, 7 Feb, 2013.).

Media reports following the guidance’s release described the action as “loosening” the drug approval requirements for Alzheimer’s disease. That characterization brought strenuous objections from FDA officials, who said the guidance was an attempt to provide standards where none existed, not a loosening of current requirements for substantial evidence of effectiveness (Also see "Standards For Early Alzheimer’s Drugs Adapted, Not Loosened, FDA’s Katz Says" - Pink Sheet, 1 Apr, 2013.).

Nevertheless, some in the CFS/ME patient community have seized on the Alzheimer’s guidance as an opening to push for faster development and approval of new treatments, including Hemispherx Biopharma Inc.’s CFS drug Ampligen (rintatolimod). FDA has twice refused to approve Ampligen, calling the efficacy and safety data inadequate and questioning the quality of the clinical development program.

At the public meeting, patient Robert Miller, who has strongly advocated for Ampligen’s approval, urged FDA to “open the door” for CFS/ME treatments just as it has opened the door for new Alzheimer’s therapies. “I want the Alzheimer’s plan,” he said. “You’re willing to loosen the restrictions.”

Several variations of a form letter have been submitted to the public docket for the CFS/ME workshop that also reference the Alzheimer’s guidance. One such letter states: “We need a stated path to drug approval for ME/CFS, with special evaluation criteria to fill the profound unmet need and empty pipeline, just like you announced for treating Alzheimer’s, ‘FDA to Ease Alzheimer’s Drug Approval.’”

At the CFS/ME meeting, Theresa Michele, clinical team leader in the Division of Pulmonary, Allergy and Rheumatology Products, sought to put the Alzheimer’s guidance into the context of FDA’s unwavering requirement for substantial evidence of efficacy and safety.

“What’s absolutely critically important is regardless of the disease, the standard of evidence is the same,” she said. “It doesn’t matter if you are looking at an orphan disease in a tiny little population, or a disease like diabetes that affects everybody, or a disease such as a rapidly progressive cancer that kills people in six months, or a disease such as chronic fatigue syndrome that’s a serious disease that’s chronically debilitating. All of these diseases have the same level required.” As to the mentions of other guidances, for example for Alzheimer’s, “they do not change the standard of evidence that’s required,” she stressed.