COVID-19 vaccines have taken most of the limelight lately, but therapies are making progress, too, with San Diego-based Atyr Pharma Inc. and Cerecor Inc., of Rockville, Md., separately offering favorable phase II news.
Atyr’s fusion protein, ATYR-1923 – also in the works for pulmonary sarcoidosis (PS) – yielded top-line phase II results in patients with severe respiratory complications who do not require mechanical ventilation. Results showed that a single dose of 3 mg/kg resulted in a median time to recovery of five and a half days (vs. six days on placebo), with 83% of patients achieving recovery in less than a week (vs. 56% placebo). The intravenous (I.V.) therapy was generally safe and well-tolerated in the 1- and 3-mg/kg treatment groups, with no drug-related serious adverse events (AEs), Atyr said.
Specifically, ATYR-1923 is made of the immunomodulatory domain of histidyl tRNA synthetase fused to the Fc region of a human antibody, and is designed as a selective modulator of neuropilin-2 that down-regulates the innate and adaptive immune response in inflammatory disease states. The trial enrolled 32 hospitalized COVID-19 patients at facilities in the U.S. and Puerto Rico. Patients were randomized 1-to-1-to-1 to a single I.V. dose of either 1 or 3 mg/kg of ATYR-1923 or placebo. They were followed for 60 days post treatment. The study was not powered for statistical significance, and was designed to evaluate safety while identifying preliminary signs of the drug’s activity as compared to placebo. Patients in the 1-mg/kg treatment arm experienced a median time to recovery of seven days, the company said. All patients in the study received standard-of-care treatment at the time of enrollment, which included Veklury (remdesivir, Gilead Sciences Inc.) and/or dexamethasone.
AEs were mostly mild or moderate in severity and generally assessed as unrelated to the study drug, Atyr said – a finding in accord with previous safety assessments of ATYR-1923, including an interim safety analysis from the ongoing phase Ib/IIa trial in PS. Two deaths happened during the study, both in the lower-dose treatment arm, which were deemed not related to the drug by an independent data safety monitoring board. Roth analyst Zegbeh Jallah called the results “supportive of [the drug’s] anti-inflammatory potential in both COVID-19 and PS.”
Atyr CEO Sanjay Shukla said during a conference call with investors that “we can look at all the patients and say [the drug] was quite successful when you compare it to other trials where some of these patients require seven, eight, sometimes 10 days of hospital stay. There was quite a bit of interest to continue the trial. I think, in particular, now that we've seen some of the randomization and have noticed that perhaps a slight skew to the more severe and high-risk groups in our treatment group. That might have explained some of the anecdotal feedback we got where there were some rather sick elderly patients that turned around rather quickly, and now we know that those patients likely received ATYR-1923 rather than placebo.”
Had the population been more balanced between groups, Shukla said, “what you might expect to see is slightly better numbers for our treatment group, if some of those sicker patients were in placebo. Placebo [results] would probably more reflect what you've seen in, for example, the [trials testing Olumiant (baricitinib, Eli Lilly and Co.) or Actemra (tocilizumab, Roche Holding AG)]. Though I will point out that those trials also enrolled a milder cohort of patients than we looked at.” He said the company “learned quite a bit in our trial and, certainly, if we had a few more of those sicker patients, better balance in the placebo population, you would have likely seen that number increase. Therefore, the difference would have been greater.”
Shares of Atyr (NASDAQ:LIFE) closed at $3.85, down 12 cents.
CERC-002 shows promise in ARDS
Cerecor’s CERC-002, a human anti-LIGHT (tumor necrosis factor superfamily member 14) monoclonal antibody, turned up phase II proof-of-concept data in patients hospitalized with COVID-19-associated pneumonia and mild to moderate acute respiratory distress syndrome (ARDS). LIGHT is the cumbersome rough acronym for “homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes.”
Eighty-three patients (82 treated) were randomized 1-to-1 to receive standard of care at the sites plus either a single dose of 1,200 mg of CERC-002 or placebo subcutaneously. Due to the protocol allowing patients to receive high flow oxygen prior to randomization, 62 were included in the intention-to-treat analysis.
The trial demonstrated robust bettering in the primary endpoint (proportion of patients alive and free of respiratory failure over the 28-day study period) compared to placebo in COVID-19 patients with ARDS treated with a single dose of CERC-002 (n=62, odds ratio [OR]=2.62, p=0.059; the data trended toward statistical significance, p≤0.05). A prespecified subpopulation of patients 60 years of age showed similar improvement in the primary endpoint (n=33, OR=3.38, p=0.054). CERC-002-treated patients in the subpopulation of patients 60 years of age also had a shorter average hospital stay compared with placebo-treated patients. The findings prove a numerical mortality benefit favoring CERC-002, with four patients dying on active drug and nine on placebo as of Dec. 31. Those data will be updated and analyzed at the 60-day timepoint, Cerecor said.
More than 90% of patients in the trial received concomitant systemic corticosteroids and more than 60% Veklury, which means the Cerecor therapy showed activity on top of the other treatment in COVID-19 ARDS. No drug-related serious AEs surfaced in the trial, nor was there any increase in infections in CERC-002-treated patients. Shares of Cerecor (NASDAQ:CERC) closed at $2.92, up 28 cents, or 10.6%.