Phase 3 Pulmonary Sarcoidosis Clinical Trial

Experimental Pharmacologic Treatment  for Pulmonary Sarcoidosis
Phase 3 Trial

Efzofitimod 

Efzofitimod is a novel immunomodulatory drug1 developed and being tested by aTyr Pharma, Inc, and Kuorin Pharmaceutical Co, Ltd.2 It is given by intravenous infusion.2 Efzofitimod (ehf-zoh-FIT-ih-mod; ATYR1923; KRP-R120) downregulates innate and adaptive immune responses in uncontrolled inflammatory disease states. It selectively binds to a receptor protein called neuropilin-2 (NRP2).1,3 This receptor is upregulated on target immune cells during inflammation, including in sarcoid granulomas that develop in the lung tissue of patients with sarcoidosis.4 By targeting NRP2 to resolve aberrant immune responses, Efzofitimod presents a novel mechanism of action, and could prove an effective therapeutic alternative with less toxicity compared to current standard of care for patients with severe inflammatory diseases where there remains a high unmet medical need.1,5,6

Efzofitimod prevented inflammation and fibrosis in multiple animal models of ILD and has been shown to mediate adaptive T cell responses and prevent granuloma formation in vitro.7 Clinical proof-of-concept was established for Efzofitimod in a Phase 1b/2a study in patients with pulmonary sarcoidosis, showing satisfactory tolerance for the drug and a dose-dependent (though not statistically significant) improvement in lung function as measured by forced vital capacity (FVC) % predicted.8

A phase 3 trial is underway to test whether intravenously infused Efzofitimod reduces the mean daily oral corticosteroid use in patients with symptomatic pulmonary sarcoidosis. The drug will also be assessed for its effect on FVC and on the King’s Sarcoidosis Questionnaire (KSQ)-Lung9 score.2 The study is currently recruiting patients. To be eligible to enroll, people must be at least 18 years of age. In addition, they must meet criteria that include (but are not limited to) the following2:

  • A 6-month history of pulmonary sarcoidosis with parenchymal lung involvement, supported by tissue biopsy (if necessary) and radiological evidence
  • A Modified Medical Research Council dyspnea scale grade of ≥1 and a KSQ-Lung score of ≤70
  • Having received oral corticosteroid treatment for at least 3 months at the start of the study, with a starting dose of 7.5 to 25 mg/day for at least 4 weeks prior to the start of the study 
  • Body weight of at least 40 kg and less than 160 kg

During this phase 3 study, participants will be randomly assigned to receive intravenous infusions of one of the following treatments: Efzofitimod (3 mg/kg), Efzofitimod (5 mg/kg), or a placebo. Each participant will receive 12 doses of their assigned treatment, once every 4 weeks, with a final follow-up visit 4 weeks after the final dose (for a total of 52 weeks).2

Throughout the study, the study investigator will determine each patient’s oral corticosteroid regimen, guided by a taper schedule and rescue criteria. Each participant’s daily oral corticosteroid dose will be recorded to help to determine whether Efzofitimod is better than placebo at reducing the need for oral corticosteroids. Participants will perform FVC tests at the beginning and end of the study to determine if Efzofitimod is better than placebo at improving lung function. Additionally, participants will fill out the KSQ at the beginning and end of the study to determine whether Efzofitimod is better than placebo at positively altering the impact of sarcoidosis as reported by the participants themselves.2

A study of Efzofitimod safety showed that the incidence of side effects was similar between patients treated with Efzofitimod and patients treated with placebo. Respiratory side effects, including cough, wheezing, and dyspnea, constituted the most commonly experienced class of side effects. No grade 3 side effects were deemed possibly related to efzofitimod.

References

  1. Baughman RP, Niranjan V, Walker G, et al. Efzofitimod: a novel anti-inflammatory agent for sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2023;40(1):e2023011. Doi:10.36141/svdld.v40i1.14396
  2. Clinicaltrials.gov Efficacy and safety of intravenos efzofitimod in patients with pulmonary fibrosis. ClincalTrials.gov identifier: NCT05415137. 
  3. Xu Z, Chong Y, Crampton S, et al. ATYR1923 specifically binds to neuropilin-2, a novel therapeutic target for the treatment of immune-mediated diseases Poster. 2020.
  4. Paz S. Immunomodulatory protein ATYR1923 disrupts an in vitro model of sarcoid granuloma formation. Presented at: European Respiratory Society International Congress 2021; September 7, 2021; virtual.
  5. aTyr. ATYR1923. Accessed February 19, 2024.
  6. Bonham CA, Strek ME, Patterson KC. From granuloma to fibrosis: sarcoidosis associated pulmonary fibrosis. Curr Opin Pulm Med. 2016;22(5):484-491. doi: 10.1097/MCP.0000000000000301. 
  7. Burkart MSC, Eide L, Paz S, et al. ATYR1923 Modulates the Inflammatory Response in Experimental Models of Interstitial Lung Disease Am J Respir Crit Care Med. 2019;199:A2421. 
  8. Culver DA, Aryal S, Barney J, et al.Efzofitimod for the treatment of pulmonary sarcoidosis.Chest. 2023;163(4):881-890.  doi:10.1016/j.chest.2022.10.037
  9. King's Sarcoidosis Questionnaire. Accessed February 19, 2024.