A few weeks ago, Alnylam Pharmaceuticals indicated it might seek a speedy FDA approval for what could be the second-ever RNA interference medicine to market. After meeting with regulators, however, the Cambridge, MA, company has come up with a different plan.
Alnylam (NASDAQ: [[ticker:ALNY]]) said this morning that it won’t seek accelerated approval of an RNAi drug, givosiran, that the company is developing for acute hepatic porphyria, a rare genetic disease that causes potentially deadly bouts of abdominal pain. But at least one outside analyst doesn’t view the decision to take a slower path as a cause for concern.
Instead of trying the faster route, Alnylam will file for approval based on the full results of an ongoing Phase 3 study, Envision. Alnylam will begin putting the paperwork together for an application later this year—what’s known as a “rolling” FDA application—but won’t file it until mid-2019, assuming the study succeeds.
An “accelerated” approval is given off of a thinner body of evidence than the FDA typically requires, and is thus faster than the norm. Such an approval is tied to a drug’s ability to impact a surrogate biological marker that should lead to a positive effect. A drug developer has to then confirm those effects with additional testing. The product could be pulled from the market if it fails those tests.
In late September, Alnylam said that upon an interim look at results of its ongoing Phase 3 study, givosiran led to a statistically significant reduction of aminolevulinic acid, or ALA, in patients’ urine—a marker of acute hepatic porphyria—after three months of treatment. Alnylam had been hoping that would be enough to head to an FDA review, and disclosed in late September it might file for accelerated approval of givosiran by the end of the year if the agency were on board with the idea.
That won’t happen, however. Alnylam will first report results from the study’s main goal—whether givosiran can reduce the rate of the disease’s hallmark attacks after six months of treatment, compared to a placebo. Those results should come in “early 2019,” Alnylam said in a prepared statement Monday. Akin Akinc, the vice president and general manager of the givosiran program, said in the statement that the study enrolled quickly and those data “are expected much earlier than originally planned.”
A full approval will take longer than an accelerated nod would have. But Stifel Financial analyst Paul Matteis wrote Monday that if Alnylam had filed for accelerated approval, the Envision data would have come while the drug was in the middle of an FDA review, a potentially “complicating dynamic” that is avoided by going the more traditional route.
“This is not a surprise to us,” Matteis wrote, calling the decision a “byproduct” of fast enrollment. “We don’t view the change in the givosiran approval path (previously accelerated, now full approval) as a marker of poor management execution.”
After 16 years of work, Alnylam has just begun selling its first product, patisiran (Onpattro), the first-ever FDA-approved medicine that uses RNA interference, a method cells can use to silence a gene before it makes a harmful protein. Givosiran is next up, though the company also has experimental drugs for hemophilia and high cholesterol in late-stage testing.
