aTyr Pharma presented clinical data for Efzofitimod (ATYR1923)

A potential novel therapy, Efzofitimod (ATYR1923) is being developed by aTyr Pharma for patients with pulmonary sarcoidosis. The therapy works by selectively modulating Neuropilin-2 (NRP2) to down-regulate the innate and adaptive immune responses to resolve inflammation and prevent subsequent worsening of symptoms. aTyr presented the clinical proof-of-concept data from Phase Ib/IIa study of efzofitimod in pulmonary sarcoidosis patients at the American Thoracic Society (ATS) 2022 International Conference in San Francisco, CA demonstrating dose-dependent improvements in key physiologic and quality of life measures in the context of a steroid taper. The data from the trial showed that the drug has the potential to become a disease-modifying therapy for pulmonary sarcoidosis patients as well as for other fibrotic diseases.

Sarcoidosis is a type of inflammatory disease in which granulomas—tiny clumps of inflammatory cells—get formed at one or more parts of the body. According the DelveInsight’s estimation of prevalent cases of Sarcoidosis in the 7MM countries (the US, EU-5 (Germany, France, Italy, Spain, and the UK), and Japan, there were approximately 246,677 cases in 2018 which is estimated to reach 262,778 by 2030.

Pulmonary sarcoidosis is sarcoidosis occurring in the lungs. Nearly 90% or more of patients with sarcoidosis have lung involvement. If not given attention at the time, this condition can lead to fibrosis, which can scar the tissue permanently.

With the primary goal to achieve the quality of life in these patients and secondarily managing the inflammation that causes more permanent fibrosis and impairment of pulmonary function, the mainstay option for treatment includes corticosteroids use in the first line, whereas glucocorticoid-sparing agents and biologic agents are used in refractory/recurrent cases. The FDA-approved therapies for the treatment of sarcoidosis are prednisone, a generic corticosteroid, and H.P. Acthar Gel, a repository corticotrophin injection marketed globally by Mallinckrodt plc., which was approved in 1952 and is not widely used by physicians due to toxicity, parenteral application and cost issues.

The current treatment seems to be complex and non-standardized for clinicians and patients, and is often ineffective or may cause significant toxicity. Out of total patients with pulmonary sarcoidosis, half of them require systemic therapy and almost one third have chronic progressive disease despite having treatment. Thus, the disease presents a substantial unmet need for safer, more efficacious therapies with an ability to reduce or replace the use of long-term oral corticosteroids (OCS) therapy.

The pipeline of pulmonary sarcoidosis shows that new treatment strategies are being evaluated to develop effective treatment options. At ATS 2022, aTyr Pharma showed that the broad set of positive data and trends in the efficacy endpoints from a Phase I/II clinical trial for its lead product has provided a solid grip for a planned FDA meeting.

As per the results, the monthly dosing of efzofitimod (1, 3, or 5 mg/kg) in comparison to placebo (2:1) intravenously for 6 months showed that efzofitimod was well tolerated at all doses with no serious AEs. Concerning steroid taper and other assessments of efficacy, the study confirmed a consistent response at all doses and improvements in comparison to placebo. The study results showed steroid use reduced by 5%, 9%, and 22% at the end of the study for the 1, 3, and 5 mg/kg efzofitimod groups. These data demonstrated clinically meaningful improvement over placebo observed for symptoms and sarcoidosis specific quality of life indices in the 5 and 3 mg/kg treatment groups, supporting further development of efzofitimod as a new therapy for pulmonary sarcoidosis in advanced trials.

The company has also discussed the results with the US FDA, where they received a positive response regarding the design of the phase III study. After the successful completion of phase I/II trial, the company is moving forward on the path to establishing durability for which the company is initiating a phase III EFZO-FIT global study by this year.

The company is quite confident and flaring to have an interest in analyzing the role of the drug in other fibrotic lung diseases as well.

Among major pipeline players for pulmonary sarcoidosis, Novartis (NVS) is developing CMK389, which is an interleukin 18 inhibitor currently in phase II; Relief Therapeutics’ RLF-100 (aviptadil), an orphan designated drug candidate in phase II trials; AI Therapeutics’ LAM-001; Xentria’s XTMAB-16; SarcoMed USA is developing Inhalation SM001, a recombinant form of human deoxyribonuclease I (DNase I), with a proven mechanism of action; and others.

The analysis allows us to believe the potential of efzofitimod to be a powerful therapy in this disease space and can tap the majority of global market sales. As per DelveInsight analysis, efzofitimod has the potential to be a blockbuster drug for pulmonary sarcoidosis including other fibrotic lung diseases where the company assumed the drug will be able to show effectiveness.