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Alnylam seeks fast-track filing with biomarker data

Early filing reflects FDA desire for faster approvals

Alnylam is set to file its next RNAi drug candidate givosiran with regulators after producing strong phase 3 data.

After 15 years building its RNAi ‘gene silencing’ platform, the Cambridge, Massachusetts based biotech gained its first US and EU regulatory approval with Onpattro last month, but now looks set to file its next candidate via an FDA fast track mechanism.

The ENVISION trial looked at givosiran in patients with acute hepatic porphyrias (AHPs) a family of rare and potentially life threatening genetic diseases, and found the drug reduced levels of Urinary Aminolevulinic Acid (ALA), a key biomarker likely to predict clinical benefit.

The trial hasn’t yet produced primary endpoint data, but Alnylam is gambling that strong signals from an interim analysis including this biomarker data will be enough for the FDA to accept its filing, accelerating a potential approval by up to six months.

Alnylam's tactic reflects a broader willingness at the FDA to consider interim data and novel biomarkers at filing in order to get novel medicines to patients faster.

The interim analysis included 43 patients who were on study for at least three months, and looked to reduce AHPs, which involve debilitating neurovisceral attacks as well as chronic pain and fatigue.

The analysis showed givosiran significantly reduced urinary ALA levels in acute intermittent porphyria (AIP) patients, relative to placebo (p less than 0.001).

As of the data cut-off date, there were no deaths, and serious adverse events (SAEs) were reported in 22% (5/23) of givosiran patients and 10% (2/20) of placebo patients. One patient discontinued treatment due to an increase in liver transaminase levels, though these later returned to normal.

The FDA will pay close attention to the drug’s safety and efficacy data, with the regulator having to make a call on whether to accept the interim biomarker or hold off for the data to mature.

The company says it will discuss these data and the regulatory path ahead with the FDA, and hope to file at or around year-end 2018, with the hope of securing a fast track approval.

Akshay Vaishnaw

Akshay Vaishnaw

Akshay Vaishnaw, M.D., Ph.D., president of R&D at Alnylam said:

“With these interim results in hand, we plan to meet with the FDA to discuss the results and the overall benefit-risk profile for a potential NDA submission at or around year-end in support of an accelerated approval.”

Alnylam continues to dose patients in the ongoing ENVISION study, where enrolment was completed ahead of schedule with 94 AHP patients. Topline full study results of the primary endpoint – the annualised attack rate after six months of treatment – are expected in early 2019.

Article by
Andrew McConaghie

28th September 2018

From: Regulatory



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