Alnylam Pharmaceuticals this morning released new data that it believes to be good enough to bring the second-ever RNA interference medicine to market, a treatment for a potentially deadly, rare genetic disease called acute hepatic porphyria.
Alnylam’s (NASDAQ: ALNY) experimental drug givosiran met its main goal in a 94-patient Phase 3 study called Envision. The drug reduced the rate of the disease’s hallmark attacks of pain, fatigue, and other symptoms after six months of treatment, compared to a placebo. Givosiran also hit its marks on five of nine additional secondary goals—each markers of the disease’s severity—while missing on four others.
The drug was, however, tied to some potentially worrisome effects on patients’ kidneys and livers. Alnylam said 10 of 48 patients treated with givosiran had serious side effects, compared to 4 of 46 on placebo. Five of the givosiran patients reported chronic kidney disease, versus none on placebo. Alnylam said, however, that those problems occurred in patients whose kidneys hadn’t been working correctly when the study started. None of those patients stopped treatment.
Alnylam also saw a spike in liver enzymes in seven givosiran patients—an indicator of potential liver damage—compared to just one on placebo. One patient dropped out of the study as a result of an increase in liver enzyme levels, but the others didn’t have any significant problems.
In a research note, Stifel analyst Paul Matteis said the data show “very clear efficacy” and an “acceptable safety profile for an ultra-rare disease.”
“We would admittedly like more color on the [kidney] function [side effects] to get 100% comfortable; that being said, probably the best evidence that the risk/benefit is positive here is the extremely high retention rate as all of those patients stayed on drug,” Matteis wrote.
Nonetheless, shares ticked down around 5 percent in pre-market trading.
Alnylam will disclose the full details from the study at a medical meeting next month.
Alnylam believes the Envision results, taken together, are good enough to support approval. “Givosiran has the potential, if approved, to be a transformative medicine for AHP patients and their families,” said Akshay Vaishnaw, Alnylam’s president of R&D, in a statement.
Alnylam has already been putting together approval applications for givosiran in the U.S. and Europe, and now aims to finish them by mid-2019. There are no approved treatments for acute hepatic porphyria; givosiran could be the first.
Alnylam initially aimed to seek accelerated approval of givosiran when it reported last year that the drug 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. But Alnylam changed those plans shortly thereafter because it was able to enroll patients in the trial more quickly than expected.
If approved, the drug would be the second-ever medicine that uses RNA interference, a method cells can use to silence a gene before it makes a harmful protein. Alnylam gained notoriety for becoming the first company, after 16 years of work, to develop and win FDA approval of an RNAi drug—patisiran (Onpattro), for patients with the rare genetic disease transthyretin amyloidosis. Givosiran is next up, though the company also has experimental drugs for hemophilia and high cholesterol in late-stage testing.