Shiloh
Editor, Senior Moderator
Source: http://www.cidrap.umn.edu/cidrap/content/influenza/general/news/nov0912peramvr-jw.html
BioCryst may drop quest for US approval of peramivir
Robert Roos * News Editor
Nov 9, 2012 (CIDRAP News) ? BioCryst Pharmaceuticals Inc. signaled yesterday it will probably give up on seeking a US license for the influenza drug peramivir, a move that would reduce the already limited options for severely ill flu patients in need of an intravenous antiviral drug.
Peramivir is a neuraminidase inhibitor, like oseltamivir (Tamiflu, given orally) and zanamivir (Relenza, given by inhalation). During the 2009 flu pandemic, the Food and Drug Administration authorized emergency use of the drug in very sick patients who needed an IV neuraminidase inhibitor. The US government has supported testing of the drug.
In a statement, BioCryst said an interim analysis of a phase 3 trial of peramivir showed that it made only a small impact and that a larger sample of patients is needed to demonstrate a statistically significant difference.
"The difference between peramivir and control groups for the primary endpoint was small and the recalculated sample size was greater than the predefined futility boundary of 320 subjects," William P. Sheridan, MB BS, of BioCryst said in the statement. "Based on this information, the independent data monitoring committee (DMC) recommended that the study be terminated for futility."
Given that recommendation, the company has stopped enrolling patients in the trial, said Sheridan, who is senior vice president and chief medical officer. He added, "We are proceeding with a full analysis of unblinded data from the trial, and a final decision will be made following completion of the analysis and further discussions with our development partners; however, it is unlikely that peramivir development for US registration will continue."
BioCryst has received a total of $234.8 million worth of contracts from the US Biomedical Advanced Research and Development Authority to develop and test peramivir, according to previous reports. The last installment was a $55 million contract awarded in February 2011 for completion of phase 3 studies.
Peramivir has been licensed in Japan for several years. It is one of two drugs that were used in the United States on an emergency basis during the 2009 pandemic. The other one was an IV formulation of zanamivir. GlaxoSmithKline, maker of zanamivir, announced in early 2011 the launch of a phase 3 trial of the IV formulation.
Earlier this year, the US Centers for Disease Control and Prevention estimated that 1,274 patients received peramivir during the pandemic. In reports published in Clinical Infectious Diseases, experts said the impact and safety profile of the drug during the pandemic remained unclear, in part because of patchy data collection.
Testing peramivir has been a challenge, because the standard care for severe flu usually includes one of the licensed neuraminidase inhibitors, oseltamivir or zanamivir. Enrolling a control group to go without standard care would be unethical, so the phase 3 trial compared standard care alone, such as oseltamivir, with peramivir plus standard care.
In February 2011 BioCryst officials said they hoped to recruit for the phase 3 trial 160 patients not treated with neuraminidase inhibitors, which might not be part of standard care at some of the 265 trial sites in several countries. The aim was to "provide the greatest opportunity to demonstrate a statistically significant peramivir treatment effect," the company said in yesterday's statement.
BioCryst said it enrolled 405 patients in the trial overall, but the interim analysis involved 119 patients enrolled in the primary efficacy population. The interim analysis included comparing the time to clinical resolution in the peramivir and control groups and estimating the sample size needed to show statistical significance, the company said. But the statement offered no details on recovery time under the two treatment regimens.
See also:
Nov 8 BioCryst press release
Apr 6 CIDRAP News story "Impact of IV peramivir use in 2009 pandemic unclear"
Feb 25, 2011, CIDRAP news item about phase 3 trial
Related Jan 14, 2011, CIDRAP News item
Jul 13, 2011, CIDRAP News item
BioCryst may drop quest for US approval of peramivir
Robert Roos * News Editor
Nov 9, 2012 (CIDRAP News) ? BioCryst Pharmaceuticals Inc. signaled yesterday it will probably give up on seeking a US license for the influenza drug peramivir, a move that would reduce the already limited options for severely ill flu patients in need of an intravenous antiviral drug.
Peramivir is a neuraminidase inhibitor, like oseltamivir (Tamiflu, given orally) and zanamivir (Relenza, given by inhalation). During the 2009 flu pandemic, the Food and Drug Administration authorized emergency use of the drug in very sick patients who needed an IV neuraminidase inhibitor. The US government has supported testing of the drug.
In a statement, BioCryst said an interim analysis of a phase 3 trial of peramivir showed that it made only a small impact and that a larger sample of patients is needed to demonstrate a statistically significant difference.
"The difference between peramivir and control groups for the primary endpoint was small and the recalculated sample size was greater than the predefined futility boundary of 320 subjects," William P. Sheridan, MB BS, of BioCryst said in the statement. "Based on this information, the independent data monitoring committee (DMC) recommended that the study be terminated for futility."
Given that recommendation, the company has stopped enrolling patients in the trial, said Sheridan, who is senior vice president and chief medical officer. He added, "We are proceeding with a full analysis of unblinded data from the trial, and a final decision will be made following completion of the analysis and further discussions with our development partners; however, it is unlikely that peramivir development for US registration will continue."
BioCryst has received a total of $234.8 million worth of contracts from the US Biomedical Advanced Research and Development Authority to develop and test peramivir, according to previous reports. The last installment was a $55 million contract awarded in February 2011 for completion of phase 3 studies.
Peramivir has been licensed in Japan for several years. It is one of two drugs that were used in the United States on an emergency basis during the 2009 pandemic. The other one was an IV formulation of zanamivir. GlaxoSmithKline, maker of zanamivir, announced in early 2011 the launch of a phase 3 trial of the IV formulation.
Earlier this year, the US Centers for Disease Control and Prevention estimated that 1,274 patients received peramivir during the pandemic. In reports published in Clinical Infectious Diseases, experts said the impact and safety profile of the drug during the pandemic remained unclear, in part because of patchy data collection.
Testing peramivir has been a challenge, because the standard care for severe flu usually includes one of the licensed neuraminidase inhibitors, oseltamivir or zanamivir. Enrolling a control group to go without standard care would be unethical, so the phase 3 trial compared standard care alone, such as oseltamivir, with peramivir plus standard care.
In February 2011 BioCryst officials said they hoped to recruit for the phase 3 trial 160 patients not treated with neuraminidase inhibitors, which might not be part of standard care at some of the 265 trial sites in several countries. The aim was to "provide the greatest opportunity to demonstrate a statistically significant peramivir treatment effect," the company said in yesterday's statement.
BioCryst said it enrolled 405 patients in the trial overall, but the interim analysis involved 119 patients enrolled in the primary efficacy population. The interim analysis included comparing the time to clinical resolution in the peramivir and control groups and estimating the sample size needed to show statistical significance, the company said. But the statement offered no details on recovery time under the two treatment regimens.
See also:
Nov 8 BioCryst press release
Apr 6 CIDRAP News story "Impact of IV peramivir use in 2009 pandemic unclear"
Feb 25, 2011, CIDRAP news item about phase 3 trial
Related Jan 14, 2011, CIDRAP News item
Jul 13, 2011, CIDRAP News item