Arimoclomol Earns FDA’s Fast Track Status for ALS

Inês Martins, PhD avatar

by Inês Martins, PhD |

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The U.S. Food and Drug Administration (FDA) has given fast track designation to Orphazyme’s investigational therapy arimoclomol for the treatment of amyotrophic lateral sclerosis (ALS).

A therapy candidate is put on the FDA’s fast track program if it can treat serious conditions and fill an unmet clinical need, either because no treatments are currently available or because the potential treatment offers significant benefits over approved alternatives.

This designation is meant to accelerate the development and review of arimoclomol, facilitating discussions with the FDA and enabling the therapy to qualify for priority review and accelerated approval, provided that certain criteria are met. Arimoclomol also has been granted the status of orphan drug.

This is the third time arimoclomol has earned fast track status in the U.S., following similar designations for Niemann-Pick disease type C, a genetic obesity disorder, and sporadic inclusion body myositis, an autoimmune disease that affects muscles.

“This is the third Fast Track Designation that arimoclomol has received from the FDA, which further underlines the potential of our investigational drug, the seriousness, and high unmet medical need in the diseases that we are targeting,” Kim Stratton, CEO at Orphazyme, said in a press release.

Arimoclomol is an oral therapy that triggers an increase in the production of heat shock proteins (HSPs), a group of proteins involved in stress response that can bind to faulty proteins and help them fold properly.

One of those HSPs binds SOD1, a protein that is faulty in ALS patients carrying mutations in the SOD1 gene. Faulty SOD1 is prone to misfolding and clumping, accumulating in nerve cells and causing them to die.

Importantly, arimoclomol is able to cross the blood-brain barrier, a highly selective membrane that shields the central nervous system from the general blood circulation, having the ability to correct the misfolded SOD1 in nerve cells.

Arimoclomol was evaluated in a prior Phase 2/3 clinical trial (NCT00706147) in 36 patients with rapidly worsening ALS stemming from SOD1 mutations. The treatment was deemed safe and well-tolerated, and patients on arimoclomol experienced a slower decline than those on placebo, though these differences were not statistically significant.

The findings prompted the launch of a larger Phase 3 trial, called ORARIALS-01 (NCT03491462), which recruited 245 patients across 30 clinical sites in North America and Europe to continue studying the safety and effectiveness of arimoclomol.

Participants were enrolled within 18 months of their first weakness symptom — defined as limb weakness, swallowing or speech problems, or shortness of breath — and assigned randomly to take capsules of arimoclomol or a placebo,  for 76 weeks (about 18 months).

ORARIALS-01’s primary goal is to measure arimoclomol’s effectiveness via a combined assessment of function and survival. Secondary goals include changes in ability to perform daily tasks — assessed through the ALS Functional Rating Scale (ALSFRS-R) — changes in lung function, and the time until permanent assisted ventilation. Topline results are expected in the first half of 2021.

“We are continuing to evaluate arimoclomol in a phase 3 clinical trial in ALS and look forward to topline results from the trial in H1 2021,” said Stratton.

After completing the study, patients will have an option to participate in an open-label extension trial (NCT03836716), which will continue to explore arimoclomol’s long-term safety and effectiveness.