FDA Approval Sought for Inolimomab in Steroid-Refractory Acute GVHD

July 24, 2020

A Biologics License Application has been submitted to the FDA for inolimomab as a potential treatment for adult patients with steroid-refractory acute graft-versus-host disease, grade II-IV,.

A Biologics License Application (BLA) has been submitted to the FDA for inolimomab (Leukotac) as a potential treatment for adult patients with steroid-refractory acute graft-versus-host disease (GVHD), grade II-IV, ElsaLs Biotech announced in a press release.1

The BLA was submitted to be reviewed as part of the FDA’s Real-Time Oncology Review (RTOR) pilot program, an FDA Oncology Center of Excellence initiative to streamline the review process of therapeutic drugs.

“The increasing number of hematopoietic stem cell transplantation worldwide has triggered an increasing need for a large variety of newly approved drugs addressing the acute GVHD and especially its steroid-resistant form that [tends to] have a very poor outcome,” said David Liens, MD, chief medical officer, ElsaLys Biotech, in a statement. “Robust clinical data including a positive safety profile, obtained from over 1400 treated individuals, positions inolimomab as a meaningful therapeutic alternative for the treatment of steroid-refractory acute GVHD.”

Data from the phase 3 study INO-107 (EUDRACT 2007-005009-24) study is supporting the BLA for inolimomab. In the study, inolimomab exhibited a robust and durable response rate in patients with steroid-refractory acute GVHD. Compared with the control group of patients who received anti-thymo globulin (ATG), inolimomab also demonstrated an improvement in long-term survival. The trial aims to serve an unmet medical need for this patient population, which is known to have a low response rate and few therapeutic options.

The INO107 study was a prospective, randomized study. The primary end point of INO-107 was overall survival (OS) and the key secondary end points included overall response rate at day 29, the effect of inolimomab on survival at intermediate periods, the incidence and consequence of chronic GVHD, infections and post-transplant lymphoproliferative disease and relapse of hematologic malignancy, the total amount of steroids used during hospital stay, and safety.

The initial study data, which were presented in 2017 at the American Society of Hematology Annual Meeting, showed that the OS rate at 1 year was 46.9% in the inolimomab arm versus 39.2% in the ATG arm. The time to treatment failure between the arms did not achieve statistical significance (adjusted HR, 0.722; 95% CI, 0.445-1.173; P = .1881). Investigators, led by Gérard Socié, MD, PhD, wrote in Blood that the lack of statistical significance underscores the need for more effective therapies for the treatment of steroid-refractory acute GVHD.2

The 2 arms also demonstrated similar safety results, but treatment with inolimomab led to fewer viral infections compared with the ATG arm. At 1 year, at least 1 serious adverse event (AE) was observed in 96% of the inolimomab arm versus in 90% of the control arm. At least 1 grade 3 to 5 AE was observed in 100% of patients in the inolimomab arm versus 98% of the control arm. AEs were treatment-related in 14% of the inolimomab versus 41% of the control group. In terms of AEs leading to treatment discontinuation, discontinuation was seen in 14% of the inolimomab arm versus 4% of the control arm, and 53% of patients died due to an AE in the inolimomab arm compared with 59% of the control arm. The most common viral infection was Epstein-Barr virus, which was observed in 49% of the experimental arm versus 52.9% of the control arm.

Long-term follow-up data for the INO-107 trial were later published in a commentary letter in Blood Advances.3

At a data cutoff of May 16, 2018, the median duration of follow-up was 58.4 months. Just over 30% of patients (n = 15; 30.6%) from the inolimomab were still alive, as were 19.6% (n = 10) of patients from the ATG arm. The HR for the difference in OS between the 2 arms was 0.572 (95% CI, 0.346-0.947; 2-sided P = .030). OS favored inolimomab with an absolute difference of 11 percentage points and a relative difference of 56%. The OS result was also statistically significant. These long-term findings were found to be consistent with the 1-year analysis.

The long-term follow-up included an analysis of patients with chronic GVHD, but no statistical significance was observed (HR, 0.96; 95% CI, 0.45-2.02; P = .91). The cumulative incidence of chronic GVHD was 31% in the inolimomab group compared with 34% in the control group.

The overall conclusion of the study was that patients with steroid0-refractory acute GVHD can derive more clinical benefit from inolimomab than ATG. Socié noted that these findings warrant further clinical investigations.

“This is an important milestone for ElsaLys Biotech as we are one step closer towards potentially bringing inolimomab to patients, responding to an increasing health need,” said Christine Guillen, PharmD, CEO and co-founder of ElsaLys Biotech, in a statement.1

Inolimomab is a monoclonal antibody that targets the interleukin-2 receptor. Outside of the United States, the agent has already made regulatory process. The French National Agency for the Medicines and Health Products Safety granted Temporary Authorization for Use status to a cohort in December of 2019, including for pediatric patients. Inolimomab was accepted into the FDA’s RTOR pilot program in June 2020.

References:

1. ElsaLys Biotech announces submission of Biologics License Application to FDA for Leukotac® (inolimomab) for the treatment of graft-versus-host disease in adult patients. News release. ElsaLyc Biotech. July 23, 2020. Accessed July 24, 2020. https://bit.ly/2ZUZsli

2. Socié G, Vigouroux S, Yaloub-Agha I, et al. A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD. Blood. 2017;129(5):643-649. doi:10.1182/blood-2016-09-738625

3. Socié G, Milpied N, Yaloub-Agha, et al. Long-term follow-up of a phase 3 clinical trial of inolimomab for the treatment of primary steroid refractory aGVHD. Blood Adv. 2019;3(2):184-186. doi:10.1182/bloodadvances.2018028282