aTyr’s Immunomodulatory Therapy ATYR1923 Wins Orphan Drug Status

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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The U.S. Food and Drug Administration has granted orphan drug designation to aTyr Pharma’s experimental immunomodulatory molecule ATYR1923 for the treatment of sarcoidosis.

The therapy is being developed for severe inflammatory diseases affecting the lungs, which in sarcoidosis patients is called pulmonary sarcoidosis.

Orphan drug status is given to treatment candidates with the potential to be safe and effective in rare diseases — defined in the U.S. as those affecting fewer than 200,000 people — with no approved treatments, or in cases in which the potential therapy shows significant benefit over existing treatments.

It is meant to expedite ATYR1923’s clinical development and review by providing regulatory support and financial benefits. It also provides a seven-year marketing exclusivity period upon regulatory approval, if granted.

“The receipt of orphan drug designation for ATYR1923 for sarcoidosis is an important milestone and recognizes the unmet need for the close to 200,000 patients living with this chronic, debilitating disease,” Sanjay S. Shukla, MD, aTyr’s president and CEO, said in a press release.

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“Current treatment options for patients with pulmonary sarcoidosis are limited,” Shukla said. “By reducing steroid burden while improving lung function and measures of sarcoidosis symptoms, ATYR1923 has the potential to be a transformative, disease modifying therapy with clinically meaningful outcomes for patients.”

After the promising results of a Phase 1b/2a clinical trial (NCT03824392) in 2021, the company is planning to launch a larger study of ATYR1923 later this year. That new registrational study is meant to support a potential filing of a regulatory application seeking the therapy’s approval.

Sarcoidosis is a highly variable inflammatory disease that can lead to the formation of small clumps of immune cells — called granulomas — in virtually any organ in the body, but most commonly in the lungs.

Current treatment options for sarcoidosis include steroids, or corticosteroids, and other immunosuppressive therapies. These, however, have limited efficacy and are associated with serious adverse events (side effects) that many patients cannot tolerate over the long term.

Given directly into the bloodstream (intravenously), ATYR1923 is an immunomodulatory molecule designed to suppress damaging immune responses in inflammatory diseases. It works by binding to neuropilin-2, or NRP-2, a protein known to regulate inflammatory responses. This protein is located at the surface of the immune cells that promote inflammation and granuloma formation.

In preclinical studies, ATYR1923 was shown to lower the levels of pro-inflammatory and pro-scarring molecules, and to significantly lessen inflammation-dependent scarring. As such, the therapy is expected to reduce symptoms and improve lung function in people with pulmonary sarcoidosis.

The proof-of-concept Phase 1b/2a trial, conducted in partnership with the Foundation for Sarcoidosis Research, evaluated the safety, tolerability, and preliminary effectiveness of three monthly doses of ATYR1923 — 1, 3, or 5 mg/kg — against a placebo in 37 adults living with a pulmonary sarcoidosis diagnosis for at least six months.

That six-month study, completed in July, also assessed the therapy’s pharmacokinetics, or its movement into, through, and out of the body, as well as its immunogenicity, which refers to its ability to trigger an unwanted immune response.

Top-line results showed that all three doses of the therapy were generally safe and well-tolerated, and that the high dose (5 mg/kg) resulted in the greatest improvements in key efficacy goals relative to a placebo.

Particularly, ATYR1923’s high dose was associated with a 22% greater reduction in corticosteroid use compared with a placebo. One-third of patients in this high-dose group became corticosteroid-free, while no patient in the other groups achieved and sustained that state.

Also, participants given the high dose showed clinically meaningful improvements in lung function and general health, as well as reductions in shortness of breath, cough, and fatigue, compared with those on a placebo.

The high dose also was linked to the greatest reductions in the levels of key inflammatory and sarcoidosis biomarkers.

aTyr says ATYR1923 is a potential first-in-class immunomodulator.