Omeros announced the U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to OMS721 for the treatment of patients with high-risk hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), specifically those patients who have persistent TMA despite modification of immunosuppressive therapy. This is the second breakthrough therapy drug designation for OMS721, which last year received the designation from FDA for the treatment of Immunoglobulin A (IgA) nephropathy. OMS721 is Omeros’ lead human monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), the effector enzyme of the lectin pathway of the complement system.
“TMA is an increasingly common complication following stem cell transplantation and is devastating when conservative treatment of immunosuppressive modification fails,” said Rafael Duarte, M.D., Ph.D., F.R.C.P.(Lon), Associate Professor, Head of Hematopoietic Transplantation and Hemato-oncology Section, University Hospital Puerta de Hierro Majadahonda, Madrid, Spain, and Secretary of the European Society for Blood and Marrow Transplantation. “Patients with HSCT-TMA who cannot undergo or do not respond to modification of immunosuppressive therapy are at very high risk of death from this complication. Currently, there is no approved treatment for HSCT-TMA, which remains one of the most pressing therapeutic needs in the field of HSCT. The impressive effect on survival and other results seen in OMS721-treated patients are quickly apparent following initiation of OMS721 therapy and can’t be explained by other factors. The HSCT community looks forward to the drug’s broad availability for our patients.”
Breakthrough therapy designation was granted based on data from Omeros’ Phase 2 clinical trial evaluating OMS721 in patients with high-risk HSCT-TMA. To be eligible for enrollment in the clinical trial, HSCT-TMA patients are required to be adults with post-transplant TMA persisting for at least two weeks following immunosuppressive regimen modification (conservative treatment) or more than 30 days post-transplant. This population was chosen to represent a population at risk for poor outcomes, including mortality. These patients often have serious, life threatening co-existing conditions, and mortality rates have been reported to be as high as 100 percent. As reported previously, the estimated median survival for OMS721-treated patients was an order of magnitude greater than that for a matched historical control (p<0.0001). Further analysis of the data examined 100-day mortality, an important endpoint previously used as an approval endpoint in HSCT. That analysis also showed that OMS721-treated patients had improved survival relative to the historical control (53% vs 10%; p = 0.0002). As previously reported, biomarkers of disease (i.e., mean platelet count and mean levels of lactate dehydrogenase and haptoglobin) demonstrated statistically significant improvement. Study patients also showed substantial improvement in red blood cell and platelet transfusion requirements. Other serious co-existing conditions in the patients treated with OMS721 included graft versus host disease (GvHD), cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies.
FDA’s breakthrough therapy designation enables expedited development and review of a drug candidate for the treatment of a serious or life-threatening disease. Preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies is required. Benefits of breakthrough therapy designation include the eligibility for priority review of the application and rolling submission of portions of the application. FDA works closely with the company to provide guidance to determine the most efficient route to approval.
Persistent thrombotic microangiopathy is a life-threatening complication of HSCT. Approximately 20,000 HSCT procedures are performed in the U.S. annually, and TMA is reported to occur in approximately 10 to 25 percent of HSCT patients. Reported mortality in high-risk patients is greater than 90%.
OMS721 is also being evaluated in ongoing Phase 3 clinical trials in IgA nephropathy and atypical hemolytic uremic syndrome. Across all clinical trials with OMS721, the drug has been well tolerated and no safety concerns have been identified.