- BioMarin Pharmaceutical on Monday laid out its explanation for why Phase 3 results from its closely watched hemophilia A gene therapy appeared to slip from an earlier trial, pointing to differences in steroid use between the two studies.
- "We learned that the timing of steroid administration may have played a role in the Phase 3 initial interim results," BioMarin's R&D head Henry Fuchs said Tuesday at a Morgan Stanley healthcare conference. In the previous Phase 2 study, patients were given steroids on average three weeks post infusion, compared to roughly 10 weeks in the later-stage trial, a new company analysis found.
- That delay in starting steroids stems from the Phase 3 study's design, which calls for on-demand use rather than the prophylactic regimen used in Phase 2. Fuchs said the Phase 3 trial will continue as designed, but noted doctors have begun to tighten steroid use, as the company has encouraged investigators to be more alert to spikes in liver enzymes.
Investors, doctors and patients are closely tracking updates on hemophilia gene therapies, which promise one-time treatment and have rapidly progressed through clinical testing.
While BioMarin is out in front in hemophilia A, Spark Therapeutics and Sangamo Therapeutics are developing competing gene therapies. Early results from Sangamo's treatment, in particular, have put pressure on BioMarin to keep on track its gene therapy, valoctocogene roxaparvovec or valrox.
Interim Phase 3 results from May showed the therapy spurred Factor VIII expressions levels lower than what was observed in Phase 2 testing. Tuesday's update appeared designed to allay some of the investor concerns which arose in response to that update.
"I doubt anything will fully calm the waters, but we're encouraged by these findings," Fuchs said, adding he's confident earlier steroid use for the remaining patients in the Phase 3 study will lead to higher Factor VIII levels, similar to those in Phase 2.
The difference in steroid use could explain why, in seven of 12 Phase 3 patients, liver enzyme elevations were associated with decreased Factor VIII activity. That compares to just one of five Phase 2 patients who experienced decreased activity alongside increased liver enzyme counts, according to company slides presented Tuesday.
BioMarin's Fuchs said physicians are paying more attention to steroid use since the interim results in May.
"As soon as the results were available, doctors started to look at each other and said maybe we're a bit slow on the trigger on on-demand steroids, and they have already started to tighten their use of steroids," Fuchs said.
The analysis also illustrates the difficulty in answering questions on fast-moving studies with small patient numbers — attributes that can make it challenging to tease out meaningful trends in the data.
Fuchs said BioMarin's explanation came after observing "a bit of scatter" between the Phase 2 and 3 results, and wanting to determine if that reflected real differences in the studies.
U.S. and European regulatory applications are still on track to be submitted in the fourth quarter, Fuchs said.
After opening flat on Tuesday, BioMarin's stock rose by as much as 3%. Shares have traded down by about 14% since the interim Phase 3 release in May.