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 psysiocrine 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 modulstor, 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 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 now underway will evaluate the long-term effect of Resolaris in these same patients. The Phase 1/2 trial (NCT02531217) should be completed by August 2018.
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 but no results have been published yet.
The U.S. Food and Drug Administration (FDA) granted Resolaris fast-track designation earlier this year 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.
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