Hemispherx Ampligen NDA Plans Could Pose Challenge For FDA

An upcoming NDA filing for Hemispherx' chronic fatigue syndrome agent Ampligen may offer a sensitive case for FDA as it implements Commissioner McClellan's "strategic plan" for the agency.

Hemispherx has been pursuing studies of Ampligen for well over a decade without offering compelling evidence that the drug has a clear effect on the poorly understood condition.

However, the company has proven adept at garnering publicity for the potential treatment - and has kept pressure on FDA with the argument that the agency should not deny hope to chronic fatigue patients.

According to Hemispherx, sufficient evidence to support approval of Ampligen is now at hand: the drug completed Phase III trials at the end of January and results will be reported at a scientific conference in the second quarter, CEO William Carter, MD, told the Wall Street Analyst Forum's investor conference March 1 in New York.

Carter described the Ampligen development program as an "odyssey."

FDA's history with the drug goes back more than a decade. The agency put a treatment IND application for the agent on hold in 1991 due in part to concerns about acute hepatic toxicity, severe abdominal pain and irregular heartbeat seen in Phase II trials. At the same time, Hemispherx, then known as HEM Pharmaceuticals, hired a PR firm to publicize a conference presentation of Phase II data.

FDA agreed to allow Phase II/III studies to proceed in 1992. In 1997, FDA allowed Hemispherx to begin charging for the drug under a treatment protocol at a "cost-recovery" price of $300 per week. The protocol remains active (¹ (Also see "EXPANDED ACCESS DATA IMPACT ON NDAs SHOULD BE ASSESSED BY FDA, REFORM BILL CONFERENCE REPORT STATES; "FAST TRACK" PROVISIONS CODIFY ACCELERATED APPROVAL" - Pink Sheet, 24 Nov, 1997.), p. 13). In 1998, the firm was cited by FDA for illegally promoting Ampligen as safe and effective for CFS and other disorders.

Over the years, Hemispherx has found allies in Congress to press FDA to allow for greater access to Ampligen. Rep. James Greenwood (R-Pa.) urged FDA to approve the cost recovery protocol in 1997; Greenwood now chairs the House Energy & Commerce/Oversight Subcommittee.

Rep. Joe Barton (R-Texas) also pressed for access to Ampligen when he served as Oversight Subcommittee chairman during the FDA reform debate. Barton has not been involved in FDA oversight issues in recent years, but is now taking over as chairman of the full Energy & Commerce Committee (² (Also see "PhRMA CEO Search On Hold; Tauzin Will Wait On Decision" - Pink Sheet, 1 Mar, 2004.), p. 23).

Under Commissioner McClellan, FDA has embraced accelerating drug development as an active part of its mission. However, McClellan has consistently maintained that the new mission does not involve any change in regulatory standards of safety and efficacy (³ (Also see "FDA Pledges 10% Reduction In NDA Review Time As Part Of “Strategic Plan”" - Pink Sheet, 30 Jun, 2003.), p. 4).

According to Hemispherx, Ampligen is a double-stranded RNA drug that acts as an interferon enhancer and antiviral by stimulating the interferon immune cascade.

The Ampligen pivotal trials are using a primary endpoint of improved physical performance as measured by treadmill exercise tolerance testing, and "various other indices" of physical performance and cognitive activity as secondary endpoints, Carter said.

The Centers for Disease Control & Prevention website reports that while Phase II trials of Ampligen have shown "moderate improvements in cognition and performance compared to placebo" and the drug has been "mostly well-tolerated," some adverse events, such as liver damage, are "still incompletely characterized."

If approved, the agent will be the first marketed CFS therapy. The disorder has frustrated most drug development efforts; there are currently no other CFS treatments in active clinical trials, according to FDC Reports' ⁴ The NDA Pipeline.

Hemispherx is building a marketing team in the U.S. for Alferon N Injection (interferon alfa-n3), which the company acquired from Interferon Biosciences in March 2003. Hemispherx has already hired 90-95 sales reps on a contract basis, Carter said.

Hemispherx is running trials of Ampligen in metastatic renal carcinoma, HIV, hepatitis B and C, and Epstein-Barr virus-positive Hodgkin's lymphoma.