Emergency authorization for peramivir draws fast response

Oct 26, 2009 (CIDRAP News) – Requests to use the intravenous (IV) antiviral drug peramivir in hospitalized H1N1 flu patients came quickly after the government issued an emergency use authorization (EUA) Oct 23, a Centers for Disease Control and Prevention (CDC) official said today.

"We released the peramivir [EUA] at 8 p.m. Friday, which is not a great time, but the feeling was we wanted to get this approved and get the drug moving as quickly as possible," Dr. Philip J. Peters said during an educational teleconference for clinicians today.

"We have had several inquiries and have sent it out to, I believe, five hospitals so far," he said.

The Food and Drug Administration (FDA) issued the peramivir EUA to make an IV antiviral drug available for H1N1 flu patients in response to a CDC request. The existing antivirals indicated for H1N1 are oseltamivir (Tamiflu), taken orally, and zanamivir (Relenza), which is inhaled. Those routes of administration may not be feasible for critically ill patients, especially those on ventilators.

Peramivir, like oseltamivir and zanamivir, is a neuraminidase inhibitor. It is in clinical trials and has not yet gained FDA approval for general use. The FDA has been considering issuing an emergency authorization for several months, and interest in using it in severely ill H1N1 patients has grown as the pandemic has spread across the country.

Under the EUA, clinicians who want to use peramivir must fill out a set of forms available on the CDC Web site and fax them to the agency.

Previously, clinicians who wanted to use the drug for H1N1 patients faced a more involved process called an emergency-use investigational new drug (EIND) application. The drug was used in a few patients under those rules, according to BioCryst Pharmaceuticals, the manufacturer, and other experts.

"I know there are a few who have gotten better, who got it under an emergency use IND," Dr. Richard Whitley, president-elect of the Infectious Diseases Society of America and a professor at the University of Alabama in Birmingham, told CIDRAP News last week. But he said it took 48 to 72 hours to obtain the drug under the EIND rules.

Under the new EUA, the CDC will draw peramivir from the Strategic National Stockpile and send it to the requesting physician's hospital free of charge, Peters said today.

The FDA's EUA letter calls on the CDC to send the drug to hospitals "as soon as possible within 24 hours of CDC's decision" to provide it.

In a news release about the authorization, BioCryst said it has transferred enough peramivir for 1,200 treatment courses to the Department of Health and Human Services (HHS). The donation was made under the company's development contract with HHS.

"BioCryst has worked with HHS to enable the government to rapidly deploy an initial supply of peramivir, and we are prepared to deliver more," Jon P. Stonehouse, BioCryst chief executive officer, said in the release.

The company said it is completing production of about 130,000 treatment courses to prepare for orders it may receive from the United States or other governments. A treatment course is 600 milligrams (mg) once a day for 5 days.

The FDA letter says the "totality of scientific evidence" indicates that IV peramivir may be effective in H1N1 patients and that "there is no adequate, approved, and available alternative to the emergency use of peramivir administered intravenously for the treatment of 2009 H1N1 in certain adult and pediatric patients."

The EUA permits use of peramivir only in hospitalized patients, Peters noted in today's Clinical Outreach and Communication Update (COCA) call.

In clinical trials so far, peramivir has yielded outcomes similar to those for the other neuraminidase inhibitors, Peters said. One study showed comparable results for patients who received a single IV dose of peramivir and patients who received oral oseltamivir for 5 days, he reported.

"The dose we're recommending is 600 mg once a day, given intravenously, for 5 to 10 days," he said. A CDC fact sheet for clinicians provides pediatric dosing recommendations based on modeling, as no pharmacokinetic studies have been done in children, he added.

Adverse events in patients given peramivir have included diarrhea, nausea, vomiting, and neutropenia, Peters reported. Physicians who use the drug under the EUA will be asked to report any serious adverse events.

"We don't anticipate that there'll be resistance problems with peramivir," which seems to have a resistance profile similar to that of oseltamivir, Peters said. He noted that 9 oseltamivir-resistant H1N1 isolates have been found among more than 1,000 tested in the United States. Most of the resistant viruses were from patients with severe immunosuppression.

In response to a question, Peters said an IV formulation of zanamivir exists but is in a much earlier stage of clinical testing than peramivir. Under EIND rules, the formulation has been used in several patients because of concern about possible resistance to oseltamivir, he said.

"Peramivir and zanamivir are really two separate issues; it's not that one would be approved [for an EUA] and not the other," he commented. "With the body of evidence available at this time, the FDA felt there was enough information available on safety and efficacy to approve peramivir. Zanamivir could be approved in the future."

So far, between 6% and 25% of hospitalized H1N1 patients have required intensive care unit placement, Peters reported. He said three different types of clinical presentations have been seen in those cases: primary viral pneumonia, invasive bacterial co-infections, and a worsening of organ dysfunction in patients who had poor cardiopulmonary reserve because of preexisting conditions.

See also:

CDC information on peramivir EUA
http://www.cdc.gov/h1n1flu/eua/peramivir.htm

Oct 15 CIDAP News story "FDA faces decision about use of peramivir for H1N1"

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