The US Food and Drug Administration (FDA) has sent Hemispherx Biopharma a Complete Response Letter (CRL) regarding the new drug application (NDA) for rintatolimod (Ampligen) for chronic fatigue syndrome (CFS), according to a news release February 5 from Hemispherx.
The FDA declined the NDA, requesting that Hemispherx perform at least 1 more clinical trial, as well as additional nonclinical studies and data analyses before the agency would reconsider the NDA. According to a company news release, Hemispherx intends to seek an end-of-review conference with the agency.
The CRL states that data from 2 pivotal clinical studies that were submitted in the NDA do not offer substantial evidence that rintatolimod is effective in treating CFS. Because of size limitations of the safety database and several discrepancies within the submitted data, the FDA stated that the available evidence was insufficient to assess safety of rintatolimod in patients with CFS.
The FDA and Hemispherx agree that in clinical study AMP-502 the primary efficacy endpoint was met with a level of significance of P = .02. For the second study, AMP-516, the P value calculated by the FDA was .10, in disagreement with Hemispherx's analysis yielding a P value of < .05. Hemispherx therefore contends that in both pivotal clinical studies the primary efficacy endpoints were met with a statistically significant improvement.
Despite the disagreement regarding the P value, analyses of AMP-516 by the FDA and by Hemispherx both showed improvement with rintatolimod compared with placebo.
Safety data submitted by Hemispherx were from the 845 study participants assigned to rintatolimod, including 589 participants with severe CFS and more than 200 patients with CFS who received rintatolimod for 1 year or more.
Hemispherx claims that these data are sufficient to establish the safety profile of rintatolimod. At the FDA Advisory Committee meeting held December 20, 2012, 8 of 13 members voted "yes" regarding "Is the safety profile of rintatolimod adequate for approval for the treatment of CFS?"
Before submitting a formal appeal to the Office of New Drugs in the FDA's Center for Drug Evaluation and Research, Hemispherx intends to seek an end-of-review conference with the FDA about their declining the NDA for rintatolimod in CFS. Their goal is to review issues cited in the CRL, the corroborating data, and experiences of clinicians and patients regarding the benefits of rintatolimod treatment in CFS.
Hoping for FDA approval of rintatolimod. a CFS advocate and patient treated with rintatolimod since 1999 through a treatment IND began a hunger strike on January 30, 2013. Hemispherx has requested that any hunger strikes be discontinued and that patients collaborate with the FDA, the company, clinicians, and patient advocates to resolve the significant unmet need for CFS treatment.
"FDA has an important role to play in shaping the future of medical breakthroughs by bringing stakeholders together to identify and overcome challenges," FDA Commissioner Dr. Margaret Hamburg said in a previous statement.
Medscape Medical News © 2013
Cite this: FDA Nixes Rintatolimod for Chronic Fatigue Syndrome - Medscape - Feb 05, 2013.