BioCryst Pharmaceuticals released the result of its phase III study using peramivir in the treatment patients hospitalized with influenza.
About the study:
About the study:
- A phase III safety and virology study (named 303) was an open-label, randomized trial that evaluated the safety and tolerability of peramivir given intravenously as once-a-day infusion of 600 mg or a twice-a-day infusion of 300 mg.
- Patient population: adult and adolescent patients who were hospitalized with confirmed or suspected influenza infection.
- Treatment duration: 5 to 10 days
- Number of patients enrolled: 234
- Patients Age: 14 to 92
- % of patients having illness more than 48 hours: 85%
- The number patients who were administered with peramivir: 230. Of these 230 patients, 170 were previously treated with oseltamivir.
- Primary endpoint: change in the influenza virus titer in nasopharyngeal samples measured by Log10TCID50 – log10 tissue culture infective dose50
Results in short:
- This is interesting: so according to the press release only 44 patients had a positive baseline culture. So the actual number of patients that the result will be based on is 44. Of the 44 patients, 20 patients were randomized into the 300 mg twice daily group and 24 patients were randomized into the 600 mg once a day group. The result showed that
- Twice a day group: there is a 1.66 reduction in log10 TCID50 viral titer (95% CI -2.32, -0.61)
- Daily group: there is a 1.47 reduction in log10 TCID50 viral titer (95% CI -1.89, -0.75)
- Other results reported when the company combined results from the patients who had positive viral titer in nasopharyngeal cultures and patients who had influenza confirmed by other methods (RT-PCR, viral culture, or serology):
- Median time to resolution of fever: 25.3 hrs
- Time to clinical resolution: 92 hours (about 4 days)
- Time to alleviation of symptoms: 145 hours (about 5-6 days)
- Time to resumption of usual activities: 26.8 days
What can we say about this result? Although it demonstrates statistically significant in the reduction of viral titer in nasopharyngeal samples, I am unsure about the clinical significance in this case. The data did not indicate as whether this medication is better than currently available therapies. Stating number doesn’t usually mean a lot unless there is something to compare to. It’s clear that a reduction in virus titer in the nasopharyngeal has been observed. However, of all the 230 patients who were administered with peramivir, only 44 patients who were positive for virus in the nasopharyngeal samples. This is less than 25% of the enrolled patients. This might justify why the company wants to increase the number of patients being evaluated in the next phase III trial.
- In addition to releasing the results, the company has submitted a proposal to the US Department of Health & Human Services (HHS) to revise its other phase III protocol (named 301). The followings are in the proposal:
- Focus of primary efficacy analysis will be on the subset of patients who are not treated with neuraminidase inhibitors
- Increase the total number of enrolled patients and increase total number of clinical trial sites
- Increase geographic regions
- Extend enrollment timeline to beyond the end of 2011
- Peramivir, discovered by BioCryst, is a neuraminidase inhibitor.
- It was launched in Japan as RAPIACTA in January 2010 by Shionogi & co. LTD.
- In August 2010, Korea Food and Drug Administration has given Green Cross marketing and manufacturing authorization for IV peramivir to treat patients who are infected with influenza A and B viruses, including H1N1 and avian influenza.
- BioCryst and Shionogi signed an exclusive license agreement in March 2007. Under the agreement, Shionogi has exclusive rights to develop and commercialize peramivir in Japan for the treatment of seasonal and potential life-threatening human influenza.
- BioCryst and Green Cross signed an agreement in June 2006 under which Green Cross is responsible for conducting clinical trials in South Korea and BioCryst is entitled to use these data for its clinical studies program.
- Based on the gathered information, BioCryst has exclusive rights to develop and commercialize peramivir worldwide except Japan, Taiwan and south Korea.