Regeneron Hits Pause on LUMINA-1 Trial Due to Concerns with Garetosmab

Pause

Regeneron announced on Friday that it is pausing dosing of garetosmab (REGN2477), an investigational therapy, in the Phase I LUMINA-1 trial. The product was designed to address fibrodysplasia ossificans progressiva (FOP), an ultra-rate genetic disorder in which muscles, tendons and ligaments are progressively replaced by bone.

Ultimately, the decision was based on reports of fatal serious adverse events in the trial during the open-label extension. It was at this point that all patients received the active treatment. These fatalities are now being further investigated to understand if they are directly related to garetosmab. During the 28-week double-blind treatment period, there were no deaths reported.

Regeneron has shared its findings and decision with the trial’s Independent Data Monitoring Committee and regulatory authorities. It will also conduct a review of the trial data to date.

The company announced topline 28-week results from the LUMINA-1 trial back in January. At the time, garetosmab appeared to decrease total lesion activity by 25%, compared to a placebo. Patient-reported flare-ups were reportedly reduced by 50% as well, and investigator-reported adverse events of flare ups were 10% for garetosmab, versus 42% for the placebo.

"This disease is relentless and devastating, leaving many patients wheelchair-bound or locked in a position unable to move, with a dramatically curtailed lifespan,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron, at the time of the announcement. “We believe garetosmab may offer important new hope that can potentially transform the course of FOP and look forward to working closely with the FDA and other regulatory authorities to make garetosmab available."

A total of 44 patients between the ages of 18 and 60 were enrolled in LUMINA-1 from North America and Europe. The primary analysis was recorded at Week 28, and the majority of treatment emergent adverse events were mild to moderate in severity.

Regeneron isn’t the only company exploring treatments for FOP. Ipsen announced in August that it had received results from its MOVE trial, the first and only multicenter Phase III study looking into palovarotene for the treatment of FOP.

Dosing of the product was paused when futility criteria were met at a pre-specified interim analysis. Results from the trial showed a 62% reduction in the average annualized new heterotopic ossification (HO) volume in participants treated with palovarotene.

“Accumulation of HO across the body is the defining characteristic of FOP and severely limits physical function over time,” said Dr. Robert Pignolo, M.D., Ph.D., Division of Geriatric Medicine and Gerontology, Department of Internal Medicine, Mayo Clinic. “The MOVE trial provides important insight into long-awaited treatment strategies and demonstrates that the oral therapy palovarotene can reduce new HO volume, representing an important therapeutic option in FOP especially in older children and adults.”

FOP affects approximately 1.3 million people worldwide. Sporadic episodes of painful soft tissue swelling called “flare-ups” can precede HO. When HO occurs, it can lead to severe functional limitations in joint mobility.

“People living with FOP face life-threatening challenges with limited treatment options. We are encouraged by these data showing a reduction in HO volume from the MOVE trial, which hopefully will result in a new potential treatment option for the FOP community,” said Adam Sherman of the International Fibrodysplasia Ossificans Progressiva Association.

The MOVE trial had a total of 107 participants who received oral palovarotene as a chronic (5mg once daily) and episodic (20mg once daily for 4 weeks, followed by 10mg for ≥8 weeks for flare-ups and trauma) regimen. The maximum adverse event severity was mild in 32.2% of participants, moderate in 45.5%, and severe in 22.2%.

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