The US Food and Drug Administration (FDA) has granted orphan designation for MOR208, an anti-CD19 monoclonal antibody, for the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL).
The European Medicines Agency (EMA) also announced a positive opinion of the orphan medicinal product application for MOR208 to treat patients with CLL/SLL.
Researchers said MOR208 showed promise in a phase 1 study of CLL/SLL patients.
Orphan drug and orphan medicinal product status are granted by the FDA and EMA to promote the development of promising therapeutics for the treatment of rare diseases affecting fewer than 200,000 people in the US annually and no more than 5 in 10,000 people in the European Union (EU).
Orphan drug designation includes benefits such as a 7-year period of marketing exclusivity in the US and 10 years of market exclusivity in the EU after approval. Other potential advantages come in the form of protocol assistance, the ability to apply for research funding, tax credits for certain research expenses, and fee waivers for the regulatory procedures.
MOR208 development, results
MOR208 is a humanized monoclonal antibody that targets the antigen CD19 for treatment of B-cell malignancies and autoimmune diseases. The development program for MOR208 is currently in phase 2 development in CLL, B-cell acute lymphoblastic leukemia, and non-Hodgkin lymphoma.
The drug is being developed by MorphoSys AG. The development program was in-licensed from Xencor in 2010.
Researchers evaluated MOR208 (formerly known as XmAb5574) in a phase 1 study of patients with CLL/SLL and reported their results at the 2012 ASH Annual Meeting (abstract 2894). The study was sponsored by Xencor.
The study included 27 patients with relapsed or refractory CLL/SLL. The median patient age was 66 years (range, 40-84), and patients were generally high-risk. The median number of prior therapies was 4 (range, 1-14).
Patients received MOR208 at a range of doses—0.3 mg/kg, 1 mg/kg, 3 mg/kg, 6 mg/kg, 9 mg/kg, and 12 mg/kg. MOR208 was administered as an intravenous infusion on days 1, 4, 8, 15, and 22 of cycle 1, and on days 1, 8, 15, and 22 of cycle 2.
Dose escalation continued without dose-limiting toxicities until the highest dose level. At this dose, 1 patient experienced grade 4 neutropenia associated with febrile neutropenia, and the patient was taken off treatment.
All 27 patients experienced adverse events, but the majority of them were grade 1-2. The most common events were infusion reactions. These occurred in 67% (n=18) of patients and were all grade 1 or 2.
Nineteen percent of patients (n=5) experienced grade 3-4 treatment-related adverse events, including neutropenia (n=3), thrombocytopenia (n=2), increased aspartate aminotransferase (n=1), febrile neutropenia (n=1), and tumor lysis syndrome (n=1). Four of these patients were on the 12 mg/kg dose, but 1 patient who experienced neutropenia was receiving 1 mg/kg.
Eleven percent of patients experienced a partial response according to IWCLL 2008 criteria. Responses occurred at the 6 mg/kg, 9 mg/kg, and 12 mg/kg dose levels.
All objective responses occurred in patients categorized as CLL as opposed to SLL, and none of the patients with lymph nodes greater than 5 cm responded. Two patients had progressed at the 8-week evaluation point.
