FDA moves Alnylam lumasiran into Phase 3 short track, sets up shot at OK in ’20

Alnylam $ALNY may be going solo on the development of rare disease drug lumasiran after Sanofi took a pass on its option, but the FDA has come through with a major assist. The company announced today that regulators have agreed on a Phase III study design that would accelerate — should all go well — its journey to approval.

For the trial designed to test lumasiran in the ultra-rare primary hyperoxaluria type 1 (PH1), the newly reached alignment allows Alnylam to adopt a primary endpoint based on a biomarker: the reduction of urinary oxalate at six months. The FDA has also sanctioned a study size of around 25 patients with PH1.

The use of a biomarker spotlights the FDA’s willingness to let drugmakers shoot for faster OKs, rather than forcing them to wait for data on disease pathology (Alnylam notes the biomarker is “directly linked to the pathophysiology of PH1 and known to be well correlated with disease progression”).

The trial design pact with the agency also marks an advance for the late-stage pipeline at Alnylam as it waits for an expected approval of patisiran, which will launch their first commercial operations in RNAi. This biotech has been through all the ups and downs often seen with any new approach to drug development. And it’s poised for some major changes.

With the study design hammered out, Alnylam expects to start the PhIII study in mid-2018, report topline results in 2019 and, if positive, submit an NDA in early 2020.

“We are very pleased with the FDA’s shared sense of urgency to evaluate the efficacy and safety of lumasiran as a potential therapeutic option for patients as rapidly as possible,” said Pritesh Gandhi, general manager of the lumasiran program, in a statement.

Alnylam is currently conducting a Phase I/II Part B study in 20 patients. Preliminary results, announced last year, suggest that lumasiran led to a mean maximal reduction in urinary oxalate of 66% in an unblinded group of four patients, and all of them achieved urinary oxalate levels at or near the normal range. Lumasiran, an RNAi therapeutic, is designed to “reduce the hepatic levels of the [glycolate oxidase] enzyme, thereby depleting the substrate necessary for oxalate production.” It was granted a breakthrough therapy designation in March.

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