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Alnylam spotlights just how good the efficacy data are for givosiran — tamping down on safety concerns

Alnylam $ALNY took another turn on its transition lap to a fully fledged commercial biotech today, posting its detailed — and very promising — efficacy data for their RNAi drug givosiran while hoping to tamp down the fretting over safety issues that spoiled their earlier top-line announcement.

We knew going into the European Association for the Study of the Liver meeting in Vienna that the drug had a great p value — now backed up by a 90% median reduction in attacks of acute hepatic porphyria, a painful and debilitating illness with no currently approved therapies. Half of the patients ended attack free, which would make this a no-brainer for regulators.

What rattled some of the analysts last time was that the rate of serious adverse events in the drug arm was more than twice what was seen in the placebo group. A serious safety signal could hamper or torpedo any drug, and indeed we learned that several of the patients experienced serious issues triggered by the therapy. Specifically this involved cases of chronic kidney disease, pyrexia and abnormal liver function test.

Alnylam CEO John Maraganore, though, says that with this drug for this disease in these patients, it will pass muster to soon become Alnylam’s second approved therapy — a landmark event for a company that has become a standard-setter for many of the development-stage companies hoping to transition into marketing one day.

Alnylam CEO John Maraganore Getty Images


“This is a disease that’s about as bad as it gets,” Maraganore told me in a preview of today’s presentation. “It is a terrible, terrible disease, and obviously when you look at the benefit it’s pretty overwhelming.”

Maraganore knows that 2 cases of CKD won’t go unnoticed by anyone, but in balancing the risk/benefit, he says there’s no doubt that the drug will get a green light. Besides, he adds, these patients typically have a high risk of kidney disease and liver issues, which regulators will certainly take into account.

As for patients, he says, the data speak for themselves, with 93 of 94 patients going on to enroll in the extension period of the study.

“We couldn’t be more happy about the data,” he adds. “If my daughter had this disease I wouldn’t hesitate for a nanosecond” to get her on the drug. And then he threw his mother and himself into that scenario. 

Everybody gets the drug.

That has Jeferies? Maury Raycroft forecasting $600 million in peak sales by 2030. He adds:

For us, there were no surprises at EASL, and as a result we are more confident in givo’s overall profile and potential. The ph.III investigator and ALNY believe the drug can be used broadly in AHP; add’ly, both ALNY and the investigator anticipate results will continue to improve.

Some of the observers earlier also weren’t too happy about a mixed set of secondary endpoints, with the therapy scoring for several biomarkers of the disease but falling short of statistical significance on secondaries like pain and fatigue and nausea, what patients are feeling.

Maraganore conceded those points, but countered that you don’t have to hit every secondary to get an approval — true enough — and that a set of patient-reported outcomes indicated that 89% reported an improvement on therapy compared to 37% on placebo.

Maraganore is likely right about the caveats. No therapy is perfect, and regulators will bend over backwards on side effects if they can get a treatment for this disease. That leaves Alnylam coming out of EASL with a timeline that anticipates an approval by this time next year.

As of now, they’re odds-on favorites for an approval.


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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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