[Author's Note: This story has been amended to correct a mistake about the design of the study presented, and to incorporate Genocea comments about the purpose of the placebo group and 12-month placebo patient data in the upcoming Phase II trial.]
A near-doubling of a biotech stock might be assumed to be the result of a knockout trial result, but in the case of Genocea’s (NASDAQ:GNCA) 95% surge yesterday the phase II data in question should be treated with caution.
The group’s therapeutic herpes vaccine GEN-003 seems to have had a sustained impact on viral shedding, but the lack of an effect on lesion reduction versus placebo, and no placebo control at 12 months, are red flags that investors should not ignore. If anything, the data highlight the importance of generating positive results from more robust studies.
The results it presented yesterday come from a 42-day, placebo-controlled trial in 310 patients, in which patients on the active arm were additionally followed open-label for one year. The 45 placebo recipients were rolled over into a separate active trial, but data from this were not reported.
The results it presented yesterday actually come from two separate studies: a 42-day, placebo-controlled trial in 310 patients, and another in which the placebo recipients were rolled over to active treatment, with all patients followed open-label for one year.
The results Genocea reported yesterday primarily concerned viral shedding – the way herpes can spread through direct contact when the patient is showing no visible signs of disease, and thus a driver of lesions. 42 days after a three-dose course of the highest, 60/75µg GEN-003 dose, patients’ days with detectable viral shedding were cut by 55%, versus about 5% in the placebo group.
The results Genocea reported yesterday primarily concerned viral shedding – the way herpes can spread through direct contact, even when the patient is showing no visible signs of disease. 42 days after a three-dose course of the highest, 60/75µg GEN-003 dose, patients’ days with detectable viral shedding were cut by 55%, versus about 5% in the placebo group.
However, for this primary endpoint the company only provided a statistical analysis versus baseline, not against placebo. And its key argument – that the two highest GEN-003 doses broadly maintained this shedding reduction for 12 months – was likewise backed only by baseline comparison since there was no placebo control beyond 42 days.
The placebo recipients did not continue for 12 months, as the Clinicatrials.gov entry suggests they were to have done, with Genocea stating that the purpose of this arm was solely for comparative safety and tolerability purposes in the immediate post-dose period.
Worryingly, at the 42-day point at which placebo-controlled data are available, genital lesion rate was cut by about 65% in the highest two doses and the placebo group alike. At least Genocea can argue that it is seeing something akin to a dose-response – the four lowest GEN-003 doses showed unreliable efficacy.
To be fair, there is logic to what Genocea is arguing: if the conceptual leap can be made between viral shedding reduction and disease abatement then a single course of GEN-003 might give patients a year’s benefit similar to that of a current daily course of antivirals, with improved convenience.
Indeed, Genocea points out that percentage of subjects lesion-free at 12 months on the two highest GEN-003 doses is broadly similar to the label claims for Valtrex and Famvir. But these are uncontrolled measures, compared across separate studies.
At least the company can point to the fact that the two highest doses, using its intended phase III formulation, are the ones it is testing in a separate phase II trial; this is also looking at viral shedding as primary endpoint, though for 10 weeks, versus placebo.
Those initial data are due in the third quarter, followed by six-month efficacy data measuring lesion-free patient numbers, at the end of 2016. Genocea says it will follow patients – importantly, including the placebo group in this instance – out to 12 months.
Investors should remain cautious until robust, 12-month comparator data are available, and bear in mind that yesterday’s share price pop will most likely be used to raise funds for phase III, due to start next year.