An Update on Ocrelizumab: Part 1
In February Genentech-Roche announced that ocrelizumab was granted breakthrough designation by the FDA following positive phase III results from their clinical trial. Ocrelizumab is the first potential treatment for progressive MS to show both efficacy and safety in phase III trials, which is a huge milestone in the world of MS research and treatment!
Laura Kolaczkowski and I had the opportunity to speak to Dr. Peter Chin, the Principal Medical Director for Genentech-Roche, to discuss the significance of the study results and obtaining breakthrough designation. But before we get to the interview, here is a brief recap of what we know about Ocrelizumab so far:
- ocrelizumab is an experimental monoclonal antibody, which is a laboratory-produced molecule designed to mimic antibodies found in your immune system. They work by altering the immune response, and are used to treat autoimmune diseases. Tysabri, Lemtrada, and Rituxan are some examples of the monoclonal antibodies already used in the treatment of relapsing-remitting MS (RRMS), and researchers have recently been looking into treating secondary-progressive MS (SPMS) and PPMS with monoclonal antibodies. Ocrelizumab’s monoclonal antibodies target a protein known as CD20 on B cells, which are a type of white blood cell thought to contribute to myelin destruction in MS.
- ocrelizumab is similar to Rituxan (an infusion already used for some people with RRMS), but while the Rituxan is made up of more foreign proteins (30% are chimeric, or mouse proteins), ocrelizumab is a humanized monoclonal antibody. This has a distinct advantage because whenever you inject something that the body can see as foreign your immune system can develop defenses against it (antibodies), which prevent the drug from working. A humanized drug has a better chance of not being tagged as a foreign invader, which overall improves it’s odds for being safe and effective long term.
- In 2015 Genentech-Roche reported positive results from two phase III clinical trials of ocrelizumab (OPERA I and OPERA II). In the OPERA studies ocrelizumab was compared to interferon therapy when given to people with RRMS and SPMS with relapses. They found that ocrelizumab significantly reduced the number of relapses, disease progression, and the number of brain lesions. Researchers then went on to investigate whether ocrelizumab could be used to treat PPMS in the ORATORIO study.
- The ORATORIO study involved 732 people with primary progressive MS from all over the globe. Participants were randomly picked to either receive ocrelizumab or a placebo via IV infusions. Researchers compared disease progression, walking ability, lesions on MRI scans, and medication tolerance between the two groups. To date Ocrelizumab is the fist therapy to significantly impact progressive MS in a phase III study.
- Ocrelizumab is a 600mg IV infusion that is given as two 300mg infusions, 2 weeks apart. During clinical trials ocrelizumab was given every 24 weeks.
Now, back to our discussion about this exciting development with Dr. Chin! The FDA grants breakthrough designation in order to facilitate and expedite the review of potential new therapies for serious and/or life threatening conditions. “It is an acknowledgment that PPMS is an unmet medical need” says Dr. Chin, “the FDA can decide whether to grant it priority review once the application is submitted, but for now the purpose of the breakthrough designation is of facilitate an exchange between the FDA and the sponsor in order to aid in the review process.” Genentech-Roche plans to submit their application for both relapsing MS and PPMS in the first half of this year. If granted priority review the FDA could take up to 6 months to reach an approval decision, as opposed to the typical 10 months that a standard review takes.
At this point it is still too early to say whether ocrelizumab will ultimately be approved by the FDA, and when it may become available as a treatment. More news will be released in the upcoming months once the FDA application is submitted. We will be sure to keep up you up-to-date! Stay tuned for part 2 of our discussion with Dr. Chin during which we talk in more detail about the safety and effectiveness on ocrelizumab.