Investigators won’t pull back the covers from the latest mid-stage data on fitusiran for a few days yet, but Alnylam $ALNY and its Big Pharma partners at Sanofi Genzyme $SNY have fired the starter pistol on an ambitious Phase III program for the antithrombin hemophilia drug that will look to field a rival to Roche’s closely watched emicizumab (ACE910).
The companies outlined their plans for the three studies in the pivotal effort, which will collectively require 250 patients with top-line data due in mid- to late-2019.
“I think we’re going to hope to file by the end of 2019, that would be the goal,” Alnylam’s Akin Akinc, the GM of the fitusiran program, tells me. “We’re now in a time where there are lots of new approaches moving forward.”
That timeline leaves the two partners well behind Roche, which has been fielding impressive data on emicizumab, a drug that has demonstrated some strong potential in slashing the annualized bleeding rate for high-risk patients who have developed inhibitors to standard therapy. But Roche has also had to contend with thromboembolic events — blood clots — in its Phase III, which have left lingering questions about the drug’s safety profile.
“These results are at least as good as what’s been presented for emicizumab,” Alnylam CEO John Maraganore told Bloomberg late last year.
Up to now, Alnylam’s updates on its RNAi approach have highlighted some cases of elevated liver enzymes, which investigators say may be the result of hepatitis C. In any case, they say they have been able to continue treatment, with great effect. In the latest update on the mid-stage program last December, researchers noted that the annualized bleed rate for patients was zero.
According to Akinc, Sanofi and Alnylam will be splitting the cost of the Phase III as part of their partnership agreement. Sanofi agreed to buy a minority stake in the biotech for $700 million when they mapped out their partnership. And Sanofi is committed to providing $75 million in development and regulatory milestones following a $25 million upfront due when Phase III starts.
Fitusiran’s move into the clinic comes as Alnylam continues to shift focus toward its late-stage pipeline, a crucial time in which the biotech will be expected to meet some high expectations on performance, particularly after Alnylam was forced to scrap revusiran last fall after safety problems scuttled the work.
Fifty hemophilia A and B patients with inhibitors to current standard of care receiving prior on-demand therapy will be enrolled for one study. Another 100 patients without inhibitors will be in a separate study. And the third is recruiting 100 patients with hemophilia A or B with or without inhibitors receiving prophylaxis therapy as prior standard of care. In this study, patients will receive standard of care prophylaxis for six months and then transition to fitusiran treatment for seven months. The annualized bleeding rate – the classic primary endpoint for these studies — will be prospectively measured in both periods.
The move by Alnylam and Sanofi comes one day after Shire filed an IND for their hemophilia gene therapy program. Gene therapy could one day provide a once-and-done approach to fixing hemophilia and that prospect has attracted several players into the field.
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