Resolaris (ATYR1940) is a first-in-class intravenous protein therapy being developed by aTyr Pharma to treat rare myopathies with excessive immune cell involvement in affected muscle tissue, namely facioscapulohumeral muscular dystrophy (FSHD), early onset FSHD, and limb-girdle muscular dystrophy 2B (LGMD2B).

Myopathies like FSHD and LGMD are muscle diseases characterized by muscle deterioration and weakness in which immune cells invade diseased muscle, and for which no approved treatments exist. The company hopes the drug will improve muscle strength and quality of life.

How Resolaris works

It is developed through physiocrine biology, namely aTyr’s Resokine pathway. This pathway is believed to promote skeletal muscle homeostasis and resets the immune system to control or reduce tissue damage while maintaining its normal activity.

Resolaris derives from a naturally occurring protein released by human skeletal muscle cells grown in the laboratory. This protein is called histidine aminoacyl tRNA synthetase (HARS), which is part of the Resokine pathway.

By mimicking the HARS protein, Resolaris harnesses the Resokine pathway and acts as an immune system modulator, interacting with T-cells to “put a brake” on T-cell activation.

Resolaris in clinical trials

aTyr Pharma tested it under a clinical development program consisting of Phase 1b/2 clinical trials to treat patients with FSHD, early onset FSHD, and LGMD. It tested the efficacy, safety, tolerability, pharmacokinetics and activity of Resolaris in a Phase 1/2 clinical trial (NCT02239224) for the treatment of FSHD patients in the United States and Europe.

Results showed that Resolaris is safe and well-tolerated in FSHD patients. More importantly, the quality of life and muscle strength of patients treated with Resolaris improved compared to those on placebo, as assessed by individualized neuromuscular quality of life (INQoL) and manual muscle testing (MMT) scores.

An extension of this study evaluated the long-term effect of Resolaris in 9 of these same patients. The Phase 1/2 trial (NCT02531217) completed in March of 2017. Results showed no significant trend of worsening in MMT or INQoL assessment scores. Three of the nine participants had reactions related to the infusion and were discontinued from the protocol.

Another Phase 1b/2 trial (NCT02603562) investigated the safety, tolerability, and efficacy of Resolaris in eight patients ages 16 to 20 with early-onset FSHD. The treatment lasted for 12 weeks. Final results showed that Resolaris improved the muscle strength of nearly two-thirds of the patients, as assessed by MMT and INQoL. The patients tolerated Resolaris well.

Researchers also assessed the safety, effectiveness and biological activity of Resolaris in a Phase 1b/2 trial (NCT02579239) of 18 patients with LGMD2B and FSHD. The results confirmed that Resolaris has a favorable safety profile and did not suppress circulating immune cells. Data also showed that Resolaris improved muscle function in 78 percent of LGMD2B patients and 50 percent of FSHD patients. Muscle function was measured at 14 weeks by MMT.

aTyr Pharma also evaluated the long-term safety, tolerability and biological activity of Resolaris in a Phase 1/2 open-label extension trial (NCT02836418) in patients from the NCT02603562 and NCT02579239 studies. The trial was completed in April 2017. Results were combined with those from NCT02531217 and briefly summarized that many of the participants maintained or increased their MMT and INQoL scores at 24 and 36 weeks. Two of the 8 participants showed an increased immune response and were discontinued from the study.

Other details

The U.S. Food and Drug Administration (FDA) granted Resolaris fast-track designation in early 2017 to treat LGMD2B and FSHD, making it the first therapeutic candidate for the treatment of these disorders to receive the designation. The FDA and the European Commission (EC) also granted orphan drug designation for the treatment of LGMD and FSHD patients.

Fast-tracking accelerates the review of therapies for serious conditions with unmet medical needs. and orphan drug designation helps companies develop products for rare diseases, defined as those affecting fewer than 200,000 Americans. This gives them incentives such as tax credits or exemption from FDA user fees, assistance in clinical trial design, and potential market exclusivity for up to seven years if the drug is approved.

 

Last updated: Nov. 6, 2019

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Muscular Dystrophy News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Técnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.
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