By Susan Courtney
Reviewed by Dr. Jack Burks
Expedited Review of Ocrelizumab for PPMS
In February, the United States Food and Drug Administration (FDA) granted “Breakthrough Therapy Designation” for ocrelizumab, an experimental medication presently under investigation for the treatment of primary-progressive multiple sclerosis (PPMS). At this time, no treatments are available for this less-common form of MS. With this designation, the FDA affirms: (1) the medication would be used to treat a serious condition; (2) preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies; and (3) the review process would be expedited to within 60 days. Please note that ocrelizumab has not yet been submitted to the FDA for approval.
Genentech, a member of the Roche group, is developing ocrelizumab. They have submitted the brand name Ocrevus™ to the FDA for this investigational medication, noting it is the first drug for MS that has been designated as breakthrough therapy by the FDA.
Ocrelizumab is an investigational, humanized monoclonal antibody designed to selectively target CD20-positive B cells. These are a specific type of immune cell thought to be a key contributor to myelin and axonal damage, which can result in disability in people with MS. In Phase III trials, ocrelizumab was given every six months in two, 300-mg intravenous (IV) infusions. These two infusions were separated by two weeks.
According to Genentech, the breakthrough designation is based on positive results from the pivotal Phase III ORATORIO study. The trial met its primary endpoint, showing that treatment with ocrelizumab in PPMS significantly reduced the progression of clinical disability sustained for at least 12 weeks compared with placebo. Walking speed, as measured by the timed 25-foot walk, was improved by 29 percent. The incidence of adverse events associated with ocrelizumab was similar to placebo; the most common adverse events were mild-to-moderate infusion-related reactions. Additionally, MRI hyper-intense T2 lesions were reduced by ocrelizumab, and brain-volume loss as viewed on MRI was reduced by 17.5 percent.
This breakthrough designation with the expedited review period has only been granted by the FDA for the one indication, which is for the long-term treatment of PPMS as studied in the ORATORIO trial. Genentech is also studying this medication for the long-term treatment of relapsing forms of MS in the OPERA I and OPERA II trials. They plan to submit data from all three of these Phase III studies to the FDA in the first half of 2016, seeking approval for ocrelizumab in both PPMS and relapsing forms of the disease.
Trial Results Presented for Oral Ozanimod
Also in February, the 72-week Phase II results were presented from the RADIANCE trial, which studied the effectiveness of ozanimod treatment in individuals with relapsing-remitting MS (RRMS). Previously known as RPC1063, this investigational medication is now under development by Celgene Corporation.
Ozanimod is a selective S1P 1 and 5 receptor modulator. It was given as a once-daily pill in the Phase II RADIANCE trial and was compared at two different doses (0.5 mg and 1 mg) with placebo. A total of 258 RRMS patients were studied in this double-blind trial, which ran for 24 weeks and was then followed by a 48-week blinded-extension period. After the initial 24 weeks, individuals taking the placebo were randomized to either dose of the medication.
At the conclusion of the 72-week study, patients in groups taking either dose of ozanimod showed a significant decrease in the mean number of gadolinium-enhanced (GdE) lesions. A significant number of participants were also free of GdE lesions, and relapse rates were reduced as well. The most common side effects reported were minor infections, back pain, and headache. Elevated liver enzymes were seen in 3 to 4 percent of the participants. No serious cardiac events were reported. Ozanimod is now being studied in two Phase III trials, SUNBEAM and a two-year portion of RADIANCE.
Ibudilast Receives Fast Track Designation
In March, MediciNova, Inc., the biopharmaceutical company developing ibudilast (MN-166), announced that this investigational medication for progressive forms of MS has received Fast Track designation from the United States Food and Drug Administration (FDA). This designation makes the drug eligible for a quicker review period, possibly leading to an accelerated approval. It is intended for drugs under development for treating serious diseases and with the potential to address unmet medical needs for such diseases.
Once Phase III trial data are available for ibudilast, these may be submitted to the FDA (along with its New Drug Application) and the Fast Track designation would become effective. Please note that the Phase II trial will not be completed until the end of 2016, so Phase III data – needed to submit ibudilast for approval – will not be available until a much later time.
Ibudilast is an oral agent with novel immune-modulating and potential neuroprotective properties. It is being studied in both secondary-progressive MS (SPMS) and primary-progressive MS (PPMS).
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