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FDA Approves Ocrevus™ (ocrelizumab) for People with Primary Progressive MS or Relapsing MS -- First Disease-Modifying Therapy for Primary Progressive MS

March 29, 2017

"This is a real game changer.” – Cyndi Zagieboylo, President and CEO, National MS Society

SUMMARY
  • The U.S. Food and Drug Administration has approved Ocrevus™ (ocrelizumab - Genentech, a member of the Roche Group) for the treatment of primary progressive MS or relapsing MS, based on clinical trials showing significant benefits against MS relapses and progression.
  • This is the first therapy specifically approved to treat primary progressive MS.
  • Potential safety issues identified by the FDA include infusion reactions and infections. There may be an increased risk of malignancy in people taking Ocrevus.
  • Ocrevus is taken by IV infusion every six months.
  • More information about Ocrevus is available from Genentech:  1-844-OCREVUS (9am-8pm Eastern)
  • Additional details and Frequently Asked Questions below
DETAILS

The U.S. Food and Drug Administration has approved Ocrevus™ (ocrelizumab - Genentech, a member of the Roche Group) for use in the treatment of primary progressive MS and relapsing MS, making it the first therapy for the treatment of primary progressive multiple sclerosis. Ocrevus will be available as a first-line treatment, which means that there are no recommendations in the approved labeling for people to try other MS therapies before taking it. Ocrevus has not been tested in children.
 
Comments
 “As the first therapy specifically approved to treat primary progressive MS, this represents a significant milestone,” said Kathy Costello, MS, ANP-BC, MSCN, Associate Vice President of Healthcare Access at the National MS Society.
 
“We are grateful that there is finally a disease-modifying treatment for people with primary progressive MS, and also an important new option for people with relapsing MS,” said Bruce Bebo, PhD, Executive Vice President, Research, at the National MS Society. “We hope this is just the first of many new treatments approved for people with progressive MS.”
 
About Ocrevus
Ocrevus is a monoclonal antibody that binds to a molecule (CD20) on the surface of immune cells called B cells, and reduces the numbers of certain B cells that are circulating in the blood. B cells have several functions including making antibodies, and they are believed to play a role in immune-system-mediated damage to brain and spinal cord tissues in MS. Ocrelizumab is administered by intravenous infusion every 6 months. The first dose is given in two infusions, two weeks apart. Subsequent doses are given as a single infusion.
 
Potential Benefits
Primary Progressive MS: The ORATORIO study involving people with primary progressive MS, which compared Ocrevus to inactive placebo, met its primary endpoint, showing treatment with Ocrevus significantly reduced the risk of progression of clinical disability by 24% compared with placebo in 732 people. Compared to placebo, Ocrevus also reduced the time required to walk 25 feet by 29%, and decreased the volume of brain lesions.
 
Relapsing MS: In the OPERA I and OPERA II studies involving people with relapsing MS, which compared ocrelizumab to interferon beta-1a (Rebif,® EMD Serono and Pfizer), Ocrevus significantly reduced the annualized relapse rate by up to 47% compared with Rebif over two years in a total of 1,656 people with relapsing MS. In addition, Ocrevus significantly delayed confirmed progression of disability on the EDSS scale by 40% compared with Rebif. Ocrevus also significantly reduced active inflammation observed on MRI scans by up to 95%, and total damage on MRI scans by up to 83% compared with Rebif.

Potential Risks
Prescribing information and the Medication Guide (.pdf) for Ocrevus includes several warnings and precautions.
  • Ocrevus can cause a wide variety of infusion-related reactions, the most frequent being itchy skin, rash, irritation in the throat, flushed face or fever, headache or other symptoms. In rare cases, these can be life-threatening. Infusion reactions occur most frequently with the first infusion, and they can occur up to 24 hours after the infusion. As a precaution, people are administered a steroid and antihistamine before their infusion and monitored at least one hour after infusion.
  • Ocrevus increases the risk of infection, including respiratory tract infections and herpes infections. Ocrevus administration should be delayed in people with an active infection, and vaccination with live or live-attenuated vaccines is not recommended during treatment and not until B cells have been repopulated following treatment.
  • There may be an increased risk of malignancy (cancers), including breast cancer, in people taking Ocrevus. Individuals using Ocrevus should follow standard breast cancer screening guidelines.The clinical trial results and ongoing monitoring of trial participants indicate an imbalance in the number of cancers that occurred in individuals treated with Ocrevus compared to those who were on interferon in the relapsing remitting trial and those on placebo in the primary progressive trial.The numbers are too small to know for sure if this is related directly to Ocrevus. This imbalance will require continued careful observation, evaluation, and data in larger numbers of individuals.
  • PML: Although no cases of PML (progressive multifocal leukoencephalopathy), a serious brain infection, occurred in clinical trials, PML has been observed in people taking related medications for other conditions. Typical symptoms are diverse, progress over days to weeks and include progressive weakness on one side of the body or clumsiness, vision disturbances, and changes in thinking, memory, orientation and personality.
  • Hepatitis B Virus Reactivation: Although no cases of hepatitis B virus reactivation have been reported in people taking Ocrevus, they have occurred in people taking similar medications. Before initiating treatment with Ocrevus, individuals should have a blood test to detect hepatitis B virus. 
For more information, people with MS can contact Genentech at: 1-844-OCREVUS (9am-8pm Eastern)
 
For people who qualify, Genentech plans to offer patient assistance programs through Genentech Access Solutions: (866) 4ACCESS/(866) 422-2377 or http://www.Genentech-Access.com.
 
Comment on Pricing
The approval of Ocrevus is an exciting milestone for people with primary progressive MS and an encouraging new option for people with relapsing forms of the disease. The National MS Society applauds Genentech for their leadership in setting the wholesale acquisition cost (or list price) of Ocrevus at $65,000 per year -- nearly 20 percent below the current market average for an MS treatment. The continually escalating prices of MS disease-modifying therapies are creating barriers to people with MS getting these life-changing medications. Through its action on Ocrevus, Genentech is changing industry dynamics so that more people can access the life-changing treatments they need to live their best lives. We encourage other companies to follow suit, creating a drug pricing trend that keeps patients first. 
 
Resources
-Read the press release from the FDA
-Download the prescribing information
-Read the FDA "Snapshot" describing the clinical trials of Ocrevus
-Read details of the clinical trials of Ocrevus in two papers published in the December 21, 2016 issue of the New England Journal of Medicine:
“Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis”
(Dr. Xavier Montalban and others)
“Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis”
(Dr. Stephen Hauser and others)  

Ocrevus is a trademark of Genentech, a member of the Roche Group.
Rebif is a registered trademark of Merck KGaA and EMD Serono, Inc.



FAQ About FDA Approval of Ocrelizumab – brand name Ocrevus™ – for Primary Progressive and Relapsing Forms of MS

Q. What is Ocrevus?
A. Ocrevus™ (ocrelizumab - Genentech, a member of the Roche Group) is a monoclonal antibody that binds to a molecule (CD20) on the surface of immune cells called B cells, and reduces the numbers of certain B cells that are circulating in the blood. B cells have several functions including making antibodies, and they are believed to play a role in immune-system-mediated damage to brain and spinal cord tissues in MS.
 
Q. What types of MS is Ocrevus approved to treat?
A. The FDA has approved ocrelizumab for the treatment of adults with primary progressive MS and with relapsing MS.
 
Q. Will everyone who has primary progressive MS benefit from Ocrevus?
A. We don’t know, since like all clinical trials, the Ocrevus trial in primary progressive MS limited the characteristics of people who could participate. The trial only included people who were aged 18 to 55, who had an EDSS (Expanded Disability Status Scale – a scale to assess neurological functioning used in clinical trials) score of up to 6.5 (meaning they were able to walk with the help of a walker or bilateral crutches or other devices on both sides), and who had evidence of immune proteins in a test of their spinal fluid (“oligoclonal bands”). It is not possible to predict how a specific individual will respond to treatment. The use of Ocrevus in clinical practice will help determine who is likely to benefit.
 
Q. Will Ocrevus help people with secondary progressive MS who are no longer experiencing relapses?
A. We don’t know. So far, the clinical trials of Ocrevus have involved people with relapsing forms of MS and primary progressive MS. Results were announced as positive for the trials in these populations. There is no data yet on whether Ocrevus may be effective in those people with secondary progressive MS who are no longer experiencing relapses.
 
Q. How is ocrelizumab taken?
A. Ocrevus is administered by intravenous (into a vein) infusion every 6 months. At the beginning of treatment there are two doses separated by 14 days. After that, there is a single infusion every 6 months.
 
Q. When will ocrelizumab be available by prescription?
A. According to Genentech, people may talk to their MS doctors now about taking Ocrevus. The company expects supplies of the therapy to be available in about two weeks (around the week of April 4, 2017). Accessing the medication also depends on issues related to an individual’s health insurance.
 
Q. How effective is Ocrevus in primary progressive MS?
A. The ORATORIO study involving people with primary progressive MS, which compared Ocrevus to inactive placebo, met its primary endpoint, showing treatment with Ocrevus significantly reduced the risk of progression of clinical disability by 24% compared with placebo in 732 people. Compared to placebo, Ocrevus also reduced the time required to walk 25 feet by 29%, and decreased the volume of brain lesions.
 
Q. How effective is ocrelizumab in relapsing MS?
A. In the OPERA I and OPERA II studies involving people with relapsing MS, which compared ocrelizumab to interferon beta-1a (Rebif,® EMD Serono and Pfizer), Ocrevus significantly reduced the relapse rate by up to 47% compared with Rebif over two years in a total of 1,656 people with relapsing MS. In addition, Ocrevus significantly delayed confirmed progression of disability on the EDSS scale by 40% compared with Rebif. Ocrevus also significantly reduced active inflammation observed on MRI scans by up to 95%, and total damage on MRI scans by up to 83% compared with Rebif.

Q. Should individuals who have relapsing MS switch from their current therapy to Ocrevus?
A. The decision about whether to take Ocrevus should be made in collaboration with your MS doctor, taking into account a variety of factors including the effectiveness of any therapy you are currently using, the potential risks and benefits, as well as costs and lifestyle factors. Important questions to be considered and discussed with your doctor in terms of Ocrevus include:
  • How am I doing on my current therapy?
  • What is my tolerance for the risk of known side effects?
  • What is my tolerance for the risk of adverse consequences that might emerge with longer-term use?
  • How will my medication choice affect my ability or plans to become pregnant? 
Q. If I have been taking another disease-modifying therapy for MS, how long will I have to wait before starting the Ocrevus?
A.  There is no wash-out or waiting time currently established or recommended for switching from another therapy to Ocrevus. Therefore a decision to wait or proceed needs to be made in collaboration with your MS doctor.
 
Q. What are the potential side effects of Ocrevus?
A. Prescribing information (.pdf) for Ocrevus includes several warnings and precautions.
  • Ocrevus can cause a wide variety of infusion-related reactions, the most frequent being itchy skin, rash, irritation in the throat, flushed face or fever, headache or other symptoms. In rare cases, these can be life-threatening. Infusion reactions occur most frequently with the first infusion, and they can occur up to 24 hours after the infusion. As a precaution, people are administered a steroid and antihistamine before their infusion and monitored at least one hour after infusion.
  • Ocrevus increases the risk of infection, including respiratory tract infections and herpes infections. Ocrevus administration should be delayed in people with an active infection. Vaccinations need to be administered at least 6 week prior to starting Ocrevus and vaccination with live or live-attenuated vaccines is not recommended during treatment and not until B cells have been repopulated following treatment.
  • PML: Although no cases of PML (progressive multifocal leukoencephalopathy), a serious brain infection, occurred in clinical trials, PML has been observed in people taking related medications. Typical symptoms are diverse, progress over days to weeks and include progressive weakness on one side of the body or clumsiness, vision disturbances, and changes in thinking, memory, orientation and personality.
  • Hepatitis B Virus Reactivation: Although no cases of hepatitis B virus reactivation have been reported in people taking Ocrevus, they have occurred in people taking similar medications. Before initiating treatment with Ocrevus, individuals should be given a blood test to detect hepatitis B virus. 
Although there is long-term safety data available on other medications that work in a similar fashion (those medications that deplete B cells), the long-term safety of Ocrevus is unknown at this time.
 
Q. Is there a risk of malignancy with Ocrevus?
A. There may be an increased risk of malignancy (cancers), including breast cancer, in people taking Ocrevus. Individuals using Ocrevus should follow standard breast cancer screening guidelines. The clinical trial results and ongoing monitoring of trial participants indicate an imbalance in the number of cancers that occurred in individuals treated with Ocrevus compared to those who were on interferon in the relapsing remitting trial and those on placebo in the primary progressive trial. The numbers are too small to know for sure if this is related directly to Ocrevus. This imbalance will require continued careful observation, evaluation, and data in larger numbers of individuals.
 
Q. Has Ocrevus been proven to be more effective than other disease-modifying therapies?
A. Ocrevus has only been compared to Rebif® (interferon beta-1a, EMD Serono and Pfizer). In two phase III studies in a total of 1,656 people with relapsing MS (people with relapsing-remitting MS and those with secondary-progressive MS who were experiencing relapses), Ocrevus significantly reduced relapse rates after two years compared to Rebif. Ocrevus has not been compared in clinical trials to other disease-modifying therapies.
 
Q. How long would a person take Ocrevus?
A. There is no specified time limit for taking Ocrevus. Like with other disease modifying medications, Ocrevus would likely be continued if the person’s MS is stable, and is experiencing no adverse events or new safety issues that could be ascribed to the medication.
 
Q. Will people taking Ocrevus have to get any special medical tests or monitoring?
A. Your doctor will need to run a blood test prior to starting this medication to test for hepatitis B infection. For individuals with relapsing MS, some MS doctors might like to have a new “baseline” MRI prior to starting a new medication. This will be at the discretion of your doctor. Individuals using Ocrevus should follow standard breast cancer screening guidelines.
 
Q. Will Ocrevus help my mobility, prevent me from getting worse or reverse my progressive disability?
A. Based on results from the clinical trials, Ocrevus is not likely to significantly reverse an individual’s disability, but may help stabilize it. In the ORATORIO trial for primary progressive MS, treatment with Ocrevus significantly reduced the risk of progression of clinical disability. This reduced risk of progression means that people taking Ocrevus in the trial were 24% less likely to demonstrate worsening of disability than people taking placebo. Ocrevus also reduced the time required to walk 25 feet, and decreased the volume of brain lesions. This means that as a group, people taking Ocrevus in the trial had a lower risk of progression, improved in their 25-ft walk speed and had reduced volume of brain lesions. However, it is not possible to predict how any one individual will respond to this or any other therapy.
 
Q. Will Ocrevus reduce disease activity in relapsing MS?
A. As a group, people taking ocrelizumab in the trial had fewer relapses, fewer new or enlarging lesions on MRI and less risk of disability worsening than people who were taking Rebif (interferon beta-1a). However, it is not possible to predict how any one individual will respond to this or any other therapy.
 
Q. Can I continue to take supplements while on Ocrevus, such as Biotin, vitamin D, vitamin B12, etc.?
A. Yes. However, it is essential that your MS doctor knows all of the prescription and over-the-counter medications, supplements and vitamins you are taking.

Q. What about vaccinations and Ocrevus? Can I have a flu shot, the pneumonia shot, and the vaccine for shingles?
A. Individuals should wait 6 weeks after being vaccinated before beginning therapy with Ocrevus. Any vaccination with live or live-attenuated viruses is not recommended during treatment with Ocrevus, and not until B cells have been repopulated following treatment. Individuals should speak to their doctors about whether the shot they are considering is available in an inactivated form.
 
Q. How often should I have an MRI while on Ocrevus?
A. Your MS doctor will guide you on how often an MRI is needed. The 2015 Revised Recommendations of the Consortium of MS Centers’ Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis suggest a brain MRI approximately 6 months after switching to a new treatment and then routine brain MRI every 6 months to 2 years for all of those with relapsing MS. Currently there are no recommendations regarding the frequency of MRI in primary progressive MS.
 
Q. Will my immune system be suppressed or compromised if I take Ocrevus? Will I be more likely to “catch” ordinary infections if I take this medication?
A. Ocrevus increases the risk of infection, including respiratory tract infections and herpes infections.
 
Q. Can I continue my other medications while I am on Ocrevus, such as Ampyra,® baclofen, and bladder medications?
A. You can continue to take all of your MS symptom management medications. However, it is essential that your MS doctor knows all of the prescription and over-the-counter medications, supplements and vitamins you are taking.
 
Q. Will I need to have a spinal tap before starting Ocrevus?
A. No.
 
Q. What if I no longer live in my own home. Can I still get Ocrevus if I live at an assisted living facility or a nursing home?
A. Whether you live at home or in a facility should not affect your ability to be on Ocrevus. However, insurance coverage may impact access to the medication.
 
Q. What are the differences between relapsing-remitting MS, secondary progressive MS and primary progressive MS?
A.
  • Relapsing-remitting MS (RRMS) is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks – also called relapses or exacerbations – are followed by periods of partial or complete recovery (remissions).
  • Secondary progressive MS (SPMS) follows an initial relapsing-remitting course. Many people who are diagnosed with RRMS will eventually transition to an SPMS course in which there is progressive worsening of neurologic function (accumulation of disability) over time.
  • Primary progressive MS (PPMS) is characterized by worsening neurologic function (accumulation of disability) from the onset of symptoms, without early relapses or remissions.
  • “Relapsing forms” of MS is a phrase that includes RRMS as well as progressive MS in those individuals who continue to experience relapses.  
Q. Is Ocrevus more likely to help me if my disability from primary progressive MS is mild versus severe?
A. It is not known who will benefit most from the use of Ocrevus. The study involving people with primary progressive MS only included individuals between the ages of 18 and 55, who had scores on the EDSS disability scale between 2.0 (minimal disability) to 6.5 (able to walk with the help of a walker or bilateral crutches or other devices on both sides). It is not possible to predict how a specific individual will respond to treatment.
 
Q. Is it better to take it earlier than later for treating progressive MS?
A. In the ORATORIO trial for primary progressive MS, the average time from diagnosis in participants was 3.3 years. It is not known how the medication will work in people who have had primary progressive MS for longer periods of time.
 
Q. Is it better to take Ocrevus earlier than later for treating relapsing MS?
A. In general, early and consistent treatment with a disease-modifying therapy is recommended. (Read more here.) However, it is not yet specifically known whether it is better to use Ocrevus earlier or later, and it is not known whether it is better to use Ocrevus before or after other disease-modifying therapies.
 
Q. Is there a point at which Ocrevus does not work?
A. There is no known point in time when this or any MS therapy may stop working effectively. Each individual will respond differently to any given therapy, and response to treatment must be assessed regularly by your MS doctor.
 
Q. What will Ocrevus cost?
A. The list price has been announced as $65,000 per year. However, the price of Ocrevus to an individual who has MS will depend on the provisions of his or her insurance coverage and the degree to which that individual will be eligible for programs designed to assist with out-of-pocket costs.
 
Q. What is the National MS Society’s response to the posted price of Ocrevus?
A. The approval of Ocrevus is an exciting milestone for people with primary progressive MS and an encouraging new option for people with relapsing forms of the disease. The National MS Society applauds Genentech for their leadership in setting the wholesale acquisition cost (or list price) of Ocrevus at $65,000 per year — nearly 20 percent below the current market average for an MS treatment. The continually escalating prices of MS disease-modifying therapies are creating barriers to people with MS getting these life-changing medications. Through its action on Ocrevus, Genentech is changing industry dynamics so that more people can access the life-changing treatments they need to live their best lives. We encourage other companies to follow suit, creating a drug pricing trend that keeps patients first. 
 
Q. Will my health insurance cover Ocrevus?
A. Coverage will depend on individual insurance plans. For people who qualify, Genentech plans to offer patient assistance programs through Genentech Access Solutions: (866) 4ACCESS/(866) 422-2377 or http://www.Genentech-Access.com.
 
Q. Where can I get information about the support that Genentech will provide to help people gain access to Ocrevus?
A. Physicians and people with MS can contact Genentech for information about access at Genentech Access Solutions: (866) 4ACCESS/(866) 422-2377 or http://www.Genentech-Access.com.
 
Q. Is Ocrevus the same as rituximab, which is a therapy used to treat some cancers?
A. No, and Ocrevus is not a derivative of rituximab. Both rituximab and Ocrevus work by depleting B cells. However, the two medications are not the same. Based on published reports, Ocrevus is manufactured differently than rituximab. Ocrevus is mostly human, and rituximab is equal parts mouse and human. These monoclonal antibodies bind to specific, but overlapping, areas of a molecule on immune B cells (called CD20 cells). There are also differences in the ways that rituximab and Ocrevus induce the death of CD20 B cells. Whether these differences are meaningful in terms of potential effectiveness in MS, or in terms of safety, is difficult to say at this time. 
 
Q. Are there other therapies in development for progressive MS?
A. Yes. The Society is closely watching clinical trials that could lead to treatments for people with progressive forms of MS. For example, positive results were recently announced from a trial of BAF-312 (Siponimod) in secondary progressive MS. 
In addition, other studies include:
  • The MS-SMART trial is testing three therapies that may have nerve-protecting properties in secondary progressive MS (with the MS Society of the U.K.).
  • The SPRINT-MS trial of Ibudilast, an oral anti-inflammatory agent, is ongoing in people with secondary progressive and primary progressive MS thanks to a unique collaboration between NIH's NeuroNEXT Network, MediciNova, and the National MS Society.
  • The MS-STAT2 study getting underway at University College London is a multicenter trial testing whether a repurposed cholesterol-lowering therapy can slow the course of secondary progressive MS; the Society is providing funding.The Society is also very interested in wellness research to identify exercise, dietary and other approaches that will help people who have MS live their best lives. The Society supports several clinical trials that are investigating dietary interventions for symptom management and for their potential to modify the disease process. 
Q: Based on these trial results, is there still a need to invest in additional research on progressive MS?
A:  Yes. We need to continue our investment in research to find solutions for progressive MS.  This trial is the first success after many disappointments. We welcome this development, but we must remain focused on finding more and better solutions for treating all forms of progressive MS. We will do this by our continued leadership in the International Progressive MS Alliance and by funding research on progressive MS through our own research programs, and by encouraging other companies to commit to developing treatments for progressive forms of MS.
 

About Multiple Sclerosis

Multiple sclerosis is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are leading to better understanding and moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.

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