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The US Food and Drug Administration (FDA) has granted fast track designation to OMS721 for the treatment of atypical hemolytic uremic syndrome (aHUS).
OMS721 is a monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (MASP-2), a key regulator of the lectin pathway of the complement system.
The FDA previously granted OMS721 orphan designation for the prevention of thrombotic microangiopathies (TMAs).
Omeros Corporation, the company developing OMS721, has released results from a phase 1 trial of the drug in healthy subjects and an ongoing phase 2 trial in patients with TMAs, including aHUS.
Early positive responses in the phase 2 trial prompted the initiation of a compassionate use program for OMS721 to allow extended treatment of 2 patients who had completed 4 weeks of dosing.
Phase 1 results
In the phase 1 trial of healthy subjects, OMS721 was well tolerated and prompted a high degree of sustained lectin pathway inhibition, according to researchers.
Seven cohorts of subjects received OMS721 or placebo by either subcutaneous injection or intravenous infusion at increasing dose levels. The researchers observed no drug-related adverse events and no clinically significant abnormalities on laboratory tests or electrocardiograms.
At the highest dose evaluated, both routes of administration prompted inhibition of the lectin pathway and achieved the pharmacologic target of sustained inhibition for at least a week.
Phase 2 results and compassionate use
In the ongoing phase 2 study, all patients are receiving OMS721. The researchers said they have observed treatment-related, clinically meaningful improvements in disease markers among the patients treated thus far.
The first cohort in this trial consisted of 3 aHUS patients treated with the lowest dose of OMS721. All 3 patients had improvements in platelet counts after treatment. Serum haptoglobin improved in 2 patients, normalizing in 1.
Serum lactate dehydrogenase levels remained normal in 1 patient, substantially decreased to close to the normal range in another, and remained elevated in the third. Creatinine levels in the 1 patient with independent renal function improved.
One patient was taken off the trial because of a serious adverse event—a localized inflammatory response often related to certain types of infections, one of which the patient previously had for 3 years while on immunosuppressive therapy. All data to date indicate no active infection in this patient.
The patient relapsed after stopping OMS721 treatment. No other significant safety issues were observed in this trial or the phase 1 trial.
The other 2 aHUS patients in this cohort continue to receive OMS721 as part of a compassionate use program. Based on their improvements in disease markers, an investigator requested that Omeros continue to provide OMS721 to these patients.
Following European regulatory approval, Omeros released the shipment of OMS721 so these patients could continue treatment beyond the period that was initially planned for the phase 2 study.
About fast track and orphan designation
The FDA’s fast track program facilitates the development of drugs intended to treat serious or life-threatening conditions and that have the potential to address unmet medical needs. Fast track status affords the company developing a drug greater access to the FDA in order to expedite the drug’s development, review, and potential approval.
Many drugs that receive fast track designation also receive priority review, and their new drug applications may be accepted by the FDA as a rolling submission, in which portions of an application are reviewed before the complete application is submitted. Priority review and rolling submission can each provide further acceleration of the FDA’s approval process.
The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.
Orphan designation provides a drug’s developer with opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, 7 years of US marketing exclusivity if the drug is approved, and other benefits.
