EQUATE Study Shows Early Response Rates in Severe Acute GVHD

Equillium announced positive interim data from the first 2 cohorts of the open label, dose escalation, phase 1b portion of the EQUATE study of itolizumab (Alzumab) in acute graft-versus-host disease (aGVHD).

The EQUATE study is evaluating itolizumab in patients with severe aGVHD as a first-line treatment concomitant with standard of care, which is typically comprised of high dose corticosteroids. Currently, there are no other therapeutics approved for this indication.

“We are very encouraged by the early response rates observed in the first 2 cohorts of aGVHD patients dosed with itolizumab, particularly since the individuals enrolled in the EQUATE study had grade III or IV disease, representing the most gravely ill patients,” Krishna Polu, MD, chief medical officer of Equillium, said in a press release. “Achieving clinical activity in a majority of these initial patients treated with itolizumab, with a time to the initial response within 15 days, is promising given the rapid progression and high acuity of aGVHD, where the time to an effective response may be critical.”

In the first 2 dose cohorts of the phase 1b open-label portion of the study, 71% of patients achieved a complete response (CR) by day 29. Specifically, in the first cohort, 2 of 4 patients achieved a CR at a dose of 0.4 mg/kg, which resulted in a CR and overall response (OR) rate of 50%. In the second cohort at a dose of 0.8 mg/kg, all 3 patients achieved a CR, resulting in a CR and OR rate of 100%. Importantly, these CRs were observed early during the itolizumab treatment course, with all patients achieving a CR within the first 15 days of treatment.

Thus far, itolizumab has been generally well tolerated and adverse events (AEs) have been consistent with those anticipated in this severely ill aGVHD patient population. Based on a thorough review of the available safety data across both cohorts, the independent data safety monitoring committee has recommended to proceed with the planned dose escalation of 1.6 mg/kg in the third cohort of the EQUATE study.

“These early response data are very promising as patients with severe aGVHD typically have a lower response to steroids,” principal investigator of the EQUATE study, John Koreth, MBBS DPhil, director of translational research and stem cell transplantation at Dana-Farber Cancer Institute, said in the release. “I am optimistic about the future of itolizumab as a potential treatment for aGVHD patients in need of effective and well-tolerated therapies. With the increase in the number of stem cell transplants to address aggressive/advanced hematologic malignancies, there continues to be significant need for new treatment options for GVHD, particularly for the patients at highest risk of mortality.”

In July 2020, Equillium indicated that its partner, Biocon Limited, conducted a randomized, controlled, open label clinical trial in India demonstrating that itolizumab significantly reduced mortality over 1 month as compared to placebo in patients hospitalized with COVID-19. In addition, it was reported that the Drugs Controller General of India granted emergency use of itolizumab for the treatment of cytokine release syndrome in patients with COVID-19 with moderate to severe acute respiratory distress syndrome in India.

Given these results, Equillium has submitted a request to the FDA for a pre-investigational new drug meeting to review a proposal to initiate a global randomized controlled clinical trial to evaluate itolizumab in hospitalized patients with COVID-19.

“We believe these data, along with the encouraging results reported by Biocon from its recent COVID-19 study, continue to support the hypothesis that itolizumab’s novel immune-modulating mechanism may have promise in addressing a range of severe immuno-inflammatory disorders,” Polu continued. “We look forward to continuing to advance our development programs as rapidly as possible.”

References:

Equillium Announces Positive Interim Data with Itolizumab in Acute GVHD Study [news release]. La Jolla, California. Published August 10, 2020. Accessed August 11, 2020. https://www.globenewswire.com/news-release/2020/08/10/2075965/0/en/Equillium-Announces-Positive-Interim-Data-with-Itolizumab-in-Acute-GVHD-Study.html#:~:text=(Nasdaq%3A%20EQ)%2C%20a,graft%2Dversus%2Dhost%20disease%20(