BioCryst Pharmaceuticals, Inc. reported preliminary findings from a phase II study with intramuscular injection of P Peramivir, the company's product for the treatment of influenza.
The study was a randomized, double blind, placebo-controlled clinical trial designed to test whether P P Peramivir, when administered acutely in high doses intramuscularly, could reduce the duration of symptoms during seasonal influenza. 344 patients who had a positive rapid antigen test indicating acute influenza illness were randomized to receive intramuscular injections of either placebo or one of two dose levels of p Peramivir (150mg and 300mg) as a single dose administered within 48 hours of symptom onset. The primary endpoint of the study was the time to alleviation of symptoms in the patients with confirmed influenza infection (n=313), the company said.
The results indicate that in the evaluable population of 313 subjects, a single dose of p Peramivir demonstrated a treatment improvement over placebo. However, the improvement was not statistically significant. With regard to the primary endpoint of median time to alleviation of symptoms, the improvement over placebo was 22.9 hours with the 150mg dose (p=0.284) and 21.1 hours with the 300mg dose (p=0.152). Based on a preliminary review, the company believes that due to the introduction of a shorter injection needle in the phase II trial compared to the phase I trial, only one-third of subjects received an adequate intramuscular injection, stated the press note.
In a post hoc analysis, 101 subjects showed evidence of adequate intramuscular injections as measured by a standard laboratory test, serum creatine kinase elevations over baseline. In this group of subjects, p Peramivir showed a larger treatment effect on the time to alleviation of symptoms. For these 101 subjects, p Peramivir showed an improvement of 64.8 hours over placebo at the 300mg dose, and an improvement of 44.6 hours over placebo at the 150mg dose. These differences were shown using the same measure of symptom alleviation as used for the primary endpoint, and they indicate a dose response in this group of patients, according to a company press release, according to a company press release.
At both doses studied, p Peramivir demonstrated a safety and tolerability profile similar to placebo, both in the total population and in the population showing evidence of intramuscular delivery.
"We are clearly disappointed that we did not achieve the primary endpoint across the entire study population. However, the goal of this phase II study was to explore the efficacy of p Peramivir and establish its safety profile in subjects with acute influenza infections as we plan for the phase III trial. In subjects that we believe received the intended dosing of p Peramivir, we saw patients achieve symptom relief up to 2.6 days faster than placebo, a result that exceeded our expectations. In addition, p Peramivir demonstrated a safety profile similar to placebo. Based on these results, we have a clear and concise plan to correct the issues identified in this study and continue our preparations to initiate our phase III program by year end," said Jon P. Stonehouse, president and chief executive officer, BioCryst Pharmaceuticals, Inc.
As per the company records, BioCryst is also currently conducting a phase II clinical trial studying an intravenous formulation of p Peramivir in hospitalized patients. That trial is designed to compare the efficacy and safety of intravenous p Peramivir to orally administered oseltamivir in patients who require hospitalization due to acute influenza.
The company is developing p Peramivir injection for the treatment of acute influenza, including infection caused by highly virulent, life-threatening strains of influenza. In January 2006 BioCryst received FDA Fast Track designation for the development of p Peramivir injection for this indication, said the company release.
According to the press release, BioCryst is advancing the clinical development of p Peramivir under terms of a contract from the US Department of Health and Human Services (DHHS) which, on January 3, 2007, awarded BioCryst a $102.6 million, four-year contract to develop p Peramivir for the treatment of influenza. Funding from the contract will support phase II and phase III product development activities including manufacturing of clinical lots, process validation, clinical studies and other product approval requirements needed for US licensure. BioCryst has retained all of its development and commercialization rights to p Peramivir worldwide except for in Japan and Korea where BioCryst recently established strategic partnerships with Shionogi & Co. in Japan, and Green Cross in Korea.
P Peramivir is a member of the class of antiviral agents that inhibit influenza viral neuraminidase, an enzyme that is essential for the spread of influenza virus within the host. P Peramivir is an inhibitor of influenza A and B neuraminidases and certain strains of influenza viruses that may be resistant to available neuraminidase inhibitors but are susceptible to p Peramivir in laboratory tests. P Peramivir injection has received Fast Track designation from US FDA and the availability of an intravenous neuraminidase inhibitor may be important in treating patients hospitalized with severe and potentially life-threatening influenza. The availability of an injectable formulation of p Peramivir could ensure appropriate dosing, which may be a concern with currently available oral or inhaled anti-influenza agents, the company informed.
BioCryst Pharmaceuticals, Inc. is a leader in the use of crystallography and structure-based drug design for the development of novel therapeutics to treat cancer, cardiovascular diseases, autoimmune diseases, and viral infections.