BioMarin lays out its PhIII strategy for its closely-watched gene therapy for hemophilia A

Henry Fuchs

When it comes to gene therapy studies, anything other than a perfect score always raises a red flag about their future in late-stage testing. And nobody gets a perfect score.

BioMarin was reminded of that lesson again today as it carefully laid out the latest promising early-stage data from a handful of hemophilia A patients who received their gene therapy BMN 270.

Their key data were good to great. Excluding one of the patients in the high dose group, leaving 6 for analysis, the mean annualized bleeding rate was reduced by 97% — from 16.3 to 0.5. “The median ABR for those same patients was reduced from 16.5 to zero. The mean annualized Factor VIII infusions were reduced by 94% from 136.7 to 8.5. The median annualized Factor VIII infusions were reduced from 138.5 to zero.” And the lower, mid-range dose also demonstrated an excellent score on bleeding and infusion rates, with a drop to zero.

So far, so good. BioMarin execs – which saw its shares $BMRN climb about 2% — say they are ready to take the high dose into a Phase III study during the 4th quarter, planning on a pivotal program with fewer than 100 patients.

But a few factors caught analysts’ eyes in examining the detailed breakdown on the data. One of the key issues was a wide variability in Factor VIII expression needed to keep hemophilia in check. Joseph Schwartz at Leerink notes this morning that investors will look closely to see if regulators are concerned by the much-higher-than-normal levels of Factor VIII in some patients before approving the Phase III design.

Interestingly, there were also several cases of elevated alanine aminotransferase (ALT) requiring a tapering treatment of corticosteroids. At one point not long ago, that sort of reaction would rattle a considerable number of investors. Now, it seems a common and easily managed side effect with no evidence of derailing therapy.

Just as Spark $ONCE is pushing ahead with its hemophilia B gene therapy, BioMarin is looking to revolutionize therapy in hemophilia. A success in the looming Phase IIIs for once-and-done treatments could put to rest a full slate of blockbuster therapies competing in this market. So look for plenty of careful data crunching in the months to come.

In the meantime, BioMarin continues to invest heavily in the work, completing a manufacturing facility for BMN 270.

BioMarin R&D chief Hank Fuchs laid out the stakes for patients:

“We are striving to make a big difference for patients with severe hemophilia A by developing a treatment that not only has the potential to eliminate bleeds, but also has the potential to eliminate the requirement for recombinant Factor VIII infusions for hemophilia A patients related to trauma, surgery and day-to-day activities.”

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