The US Food and Drug Administration (FDA) has bestowed Fast Track status upon OMS721 for an atypical hemolytic uremic syndrome (aHUS) indication currently being developed by the agent’s manufacturer, Omeros Corporation, headquartered in Seattle, Washington.1
The Fast Track program is intended to speed development, review and approval for agents formulated to combat serious and/or life-threatening conditions and unmet medical needs via the facilitation of expanded FDA access and advisory aid.2
The potential therapy, now in a Phase 2 clinical trial, represents the lead agent in the Omeros pipeline.1
The FDA announcement comes only a few months following the agent’s attainment of compassionate use status from EU regulators in April, 2015.3 OMS 721 attained Orphan Drug Status (designed to incentivize and help subsidize private sector research into rare disease treatment) from the FDA back in December, 2013.4
The treatment candidate is a human monoclonal antibody which works to target a specific enzyme - mannan-binding lectin-associated serine protease-2 (MASP-2) – which has been implicated in the etiology of aHUS.5
MASP-2, which is expressed by an identically named gene, is a key regulator of the lectin pathway. The lectin pathway is, in turn, a critical component of the immune system. When the human body sustains tissue damage or infection, the lectin pathway is 1 of the principle “highways” via which immune system response is activated. Abnormal lectin pathway function is associated with a wide range of autoimmune disorders including thrombotic microangiopathies (TMAs), a disease family of which aHUS is a member.5
Solid Phase 2 Data Drives FDA Decision
The Fast Track designation was granted on the basis of interim data derived from patients in an ongoing, interventional, multi-cohort, multi-site, international, uncontrolled, non-randomized, open label, 2-stage, dose escalation Phase 2 clinical trial that is evaluating the safety, tolerability, and clinical activity of OMS721 in adults as a prospective treatment for a range of TMAs, including aHUS.1,6
Early-stage findings focused upon the first cohort of the study, 3 aHUS patients who underwent low-dose OMS721 treatment. At 4 weeks, platelet count, serum lactate dehydrogenase and serum haptoglobin were measured as disease activity metrics. Improvements were observed across a spectrum of TMA disease markers. When compared to baseline levels, subjects demonstrated what investigators characterized as “treatment-related and clinically meaningful” outcomes in the following areas:
Platelet count improvement (all patients)
Serum lactate dehydrogenase levels, which ranged from elevated (1 patient), to normalized (1 patient), to substantially decreased to close to normal range (1 patient).
Haptoglobin improvement (2 patients) and normalization (1 patient)
Creatinine level improvement (1 patient)
Based upon the initial clinical response and tolerability demonstrated in the above cohort, the European Medicines Agency moved to extend access to OMS721 for compassionate use. Under the terms of the program, 2 of the 3 patients in the cohort will continue to undergo an OMS721 regimen at current or increased dosages. The third patient was eliminated from the trial for precautionary reasons because of an adverse event unrelated to OMS721. No other significant safety issues were observed in either the aforementioned trial or in previous OMS721 trials.1,6
Swift FDA Action Underscores Urgency
Currently, only a single therapy, eculizumab (marketed as Soliris), has obtained FDA approval for the treatment of aHUS.7
According to Gregory A. Demopulos, MD, Chairman, Chief Executive Officer, Omeros, "FDA's Fast Track designation of OMS721 for aHUS reflects the unmet need associated with this disease and recognizes the drug's potential as an important option for the treatment of aHUS."
Near-term plans for continued OMS721 development include finalization and data harvest of the currently in-process Phase 2 research initiative (expected by the end of this year), at which time, following consultations with the FDA, the commencement of phase 3 study is expected.
"We look forward to working with the FDA to streamline the development of this promising drug, and we currently remain on track to discuss with the Agency later this year both the data from our Phase 2 trial in TMAs as well as our plans for our Phase 3 program," reported Dr. Demopulos. The eventual goal of the company is to commercialize OMS721 for 1 or more therapeutic indications as a subcutaneous injection.1
The primary impact of aHUS is on kidney function. Typically, abnormally large blood clots form in small blood vessels in the kidneys, restricting or blocking blood flow. Consequences of the clotting dysfunction include hemolytic anemia, thrombocytopenia, and kidney failure.
Hemolytic anemia occurs when red blood cells are destroyed at faster rate than the body can replace them. In aHUS, premature hemolysis can occur. Red blood cells actually tear themselves apart as they attempt to squeeze past oversized clots within small blood vessels. Thrombocytopenia, characterized by a reduced level of circulating platelets in the blood, can be aHUS-related due to platelet shortages which exist as a result of an excess of platelet participation in the manufacture of abnormal clots. By far, however, the dearest toll exacted by aHUS is kidney damage and acute kidney failure that leads to end-stage renal disease in about 50% of affected patients.
1. FDA Grants "Fast Track" to Omeros' Complement Inhibitor OMS721 for aHUS [press release]. Seattle, Washington: Omeros Corporation; July 23, 2015. http://www.prnewswire.com/news-releases/fda-grants-fast-track-to-omeros-complement-inhibitor-oms721-for-ahus-300117622.html
2. FDA Website. Fast Track, Breakthrough Therapy, Accelerated Approval, Priority Review. http://www.fda.gov/forpatients/approvals/fast/ucm20041766.htm
Updated September 18, 2014. Accessed July 28, 2015
3. European Regulatory Authority Approves Clinical Investigator’s Request for Compassionate Use with Omeros Corporation’s OMS721 [press release]. Seattle, Washington. Omeros Corporation. April 14, 2015. http://investor.omeros.com/phoenix.zhtml?c=219263&p=irol-newsArticle_Print&ID=2034728
4. FDA Grants Orphan Drug Designation to Omeros' OMS721 for Complement-Mediated Thrombotic Microangiopathies [press release]. Seattle, Washington. Omeros Corporation. December 18, 2013. http://www.prnewswire.com/news-releases/fda-grants-orphan-drug-designation-to-omeros-oms721-for-complement-mediated-thrombotic-microangiopathies-236355151.html
5. Omeros Corporation website. MASP. http://www.omeros.com/pipeline/masp2.htm
Accessed July 28, 2015.
6. Staff report. Omeros's phase II OMS721 trial completes dosing, extended access for compassionate use. Center Watch News Online http://www.centerwatch.com/news-online/article/7596/omeross-phase-ii-oms721-trial-completes-dosing-extended-access-for-compassionate-use#sthash.erzZT3Bj.kqEifi9q.dpbs
Published February 26, 2015. Accessed online July 28, 2015.
7. FDA approves Soliris for rare pediatric blood disorder [press release]. Silver Spring, Maryland. US Food and Drug Administration. September 23, 2011. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm272990.htm
8. Genetics Home Reference website. Atypical-hemolytic-uremic-syndrome. http://ghr.nlm.nih.gov/condition/atypical-hemolytic-uremic-syndrome
Published July 19, 2015. Accessed July 28, 2015