Updated from 5:31 p.m. EDT
said after the market close Wednesday that preliminary results of a phase II study of peramivir to treat seasonal and life-threatening influenza didn't meet the study's primary endpoint. But a needle-length issue may have compromised results.
The study on 344 patients showed peramivir, which is being developed to treat avian influenza, to be safe and well-tolerated, but median time to alleviation of symptoms -- the primary endpoint -- wasn't statistically significant with improvement over placebo of 22.9 hours with a 150-milligram dose and 21.1 hours with the 300-mg dose. (An improvement of at least a day-and-a-half over placebo was the target.)
However, BioCryst said it believes only a third of the subjects received an adequate intramuscular injection of peramivir because a one-inch injection needle was used in the phase II trial compared to a one-and-a-half inch needle phase I trial, which also had stricter body mass index (BMI) criteria.
On a conference call Wednesday night, CEO Jon Stonehouse said that the company used the shorter needles for patient comfort, but didn't take into account differences in the BMI of different subjects and between genders, a factor that affects how far the needle has to go to reach the muscle. Not surprisingly, central to an intramuscular injection is that it reaches the muscle.
In order to determine in which patients peramivir reached the muscle, the company looked at creatine kinase (CK), an enzyme released when there's muscle injury. The company identified 101 patients that it believed showed evidence of adequate injection. Although this group is too small for statistical significance, peramivir showed an improvement of 64.8 hours over placebo at the 300-mg dose and 44.6 hours over the placebo at the 150-mg dose -- results that the company said exceeded its expectations.
Still, CK can be affected by a variety of conditions and the use of some medications. With that in mind, analysts were eager for a second indication that the population of 101 patients that BioCryst identified were for sure the ones who'd received the peramivir into the muscle -- and for confirmation that the rest of the population did not. In addition, one analyst asked, "Why not do a confirmatory phase II where you have all the wrinkles ironed out?"
Stonehouse said the virology results for the trial, "available in weeks not months," and a detailed pharmacokenetic study will provide answers, but he is confident needle length was the culprit for flimsy results. Confident enough to proceed with plans for a phase III study that will start enrolling patients before year-end.
BioCryst said the phase III study will be a 1,000-patient-plus program in two trials and whether it will be possible to complete it in one flu season will be dependent on what kind of flu season we see.
The company has fast-track designation for peramivir injection to treat acute influenza, including an infection caused by life-threatening strains of influenza, and also has a phase II study under way exploring an intravenous formulation of peramivir in hospitalized patients.
Shares closed Wednesday's regular session up 33 cents, or 2.9%, at $11.78 but were trading down $3.72, or 31.6%, at $8.06 in recent after-hours trading.