- Alnylam Pharmaceuticals will roll the dice and seek to win an accelerated approval from the Food and Drug Administration for its rare disease drug givosiran, betting that initial study results showing the treatment's beneficial effect on a biomarker will be sufficient to pass regulatory muster.
- The biotech, announcing Thursday interim data from a Phase 3 trial of givosiran, said it aims to discuss a potential submission for approval with the FDA by the end of this year. If the FDA disagrees, however, Alnylam would need another four to six months to complete the study and obtain more full results.
- Givosiran is designed to treat a group of rare diseases known as acute hepatic porphyrias (AHP), which can cause frequent attacks of severe abdominal pain as well as muscle weakness. Like Alnylam's recently approved drug Onpattro, givosiran works by "silencing" the RNA instructions used by cells to make proteins.
One month after winning a landmark approval, Alnylam is already looking to its second date with regulators.
In seeking an accelerated approval for givosiran, the biotech is counting on the FDA's willingness to consider data based on surrogate endpoints "reasonably likely" to predict a clinical benefit.
To this end, Alnylam planned its late-stage study of givosiran to include a prespecified interim check of the drug's impact on a disease marker found in urine.
That marker, a neurotoxic heme intermediate called ALA, is thought to be a trigger for AHP, Alnylam says. Phase 1 data appear to back up that claim, showing greater ALA lowering was associated with lower annualized attack rates.
Givosiran reduces ALA by targeting a liver protein called ALAS1. Silencing that protein through RNA interference should, in theory, lower ALA and translate into fewer attacks.
Data from the Phase 3 study show that, after three months of treatment, givosiran led to a statistically significant reduction in urinary ALA levels. While Alnylam didn't disclose the specific figures, it's moving on to seek a meeting with the FDA. If those discussions go well, the company could file by year's end.
Results on how treatment with givosiran affected the number of AHP attacks, however, won't be available until early 2019. If the FDA wants to wait for those data, Alnylam could be hung up on a filing for standard approval for as long as half a year.
Thursday's interim look at the study also only reports data from 43 patients. Enrollment of all 94 patients in the study completed in August.
More patients who received givosiran experienced an adverse event than those given placebo. One patient was forced to discontinue treatment after an increase in liver enzymes eight times higher than the upper limit of normal.
Shares in Alnylam initially dropped nearly 3% in early Thursday trading on the news, before recovering to close down a little more than 1%.