Tuesday, Mar 28, 2017

FDA Approves Genentech’s OCREVUS™ (Ocrelizumab) For Relapsing and Primary Progressive Forms of Multiple Sclerosis

  • First and only approved disease-modifying therapy for primary progressive form of multiple sclerosis (PPMS) – one of the most disabling forms of multiple sclerosis (MS)
  • An important new treatment option for people with relapsing forms of multiple sclerosis (RMS) demonstrating superior efficacy on the three major markers of disease activity compared with Rebif®
  • A favorable benefit-risk profile demonstrated in three large Phase III studies with a diverse patient population, including those early in the disease

South San Francisco, CA -- March 28, 2017 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) approved OCREVUS™ (ocrelizumab) as the first and only medicine for both relapsing and primary progressive forms of multiple sclerosis. The majority of people with MS have a relapsing form or primary progressive MS at diagnosis.

“The FDA’s approval of OCREVUS is the beginning of a new era for the MS community and represents a significant scientific advance with this first-in-class B cell targeted therapy,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Until now, no FDA-approved treatment has been available to the primary progressive MS community, and some people with relapsing forms of MS continue to experience disease activity and disability progression despite available therapies. We believe OCREVUS, given every six months, has the potential to change the disease course for people with MS, and we are committed to helping those who can benefit gain access to our medicine.”

In two identical RMS Phase III studies (OPERA I and OPERA II), OCREVUS demonstrated superior efficacy on the three major markers of disease activity by reducing relapses per year by nearly half, slowing the worsening of disability and significantly reducing MRI lesions compared with Rebif® (high-dose interferon beta-1a) over the two-year controlled treatment period. A similar proportion of people in the OCREVUS group experienced a low rate of serious adverse events and serious infections compared with people in the high-dose interferon beta-1a group in the RMS studies. 

In a separate PPMS Phase III study (ORATORIO), OCREVUS was the first and only treatment to significantly slow disability progression and reduce signs of disease activity in the brain (MRI lesions) compared with placebo with a median follow-up of three years. A similar proportion of people in the OCREVUS group experienced adverse events and a low rate of serious adverse events compared with people in the placebo group in the PPMS study. 

The most common side effects associated with OCREVUS in all Phase III studies included infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity. Results from these three Phase III studies were recently published in the January 19, 2017 issue of the New England Journal of Medicine (NEJM).

“This is an exciting day for everyone touched by MS, a disease that strikes in the prime of a person’s life when she or he may be starting a career or family,” said June Halper, MSN, APN-C, MSCN, FAAN, chief executive officer at the Consortium for MS Centers. “We have eagerly awaited the FDA approval of OCREVUS because it not only offers a new, highly efficacious treatment option for people with relapsing multiple sclerosis, but it is also the first disease-modifying therapy indicated for primary progressive multiple sclerosis, a highly disabling type of this chronic disease. For many people living with MS, this FDA approval is a source of hope.”

 OCREVUS will be available to people in the U.S. within two weeks. Genentech is committed to helping people access the medicines they are prescribed and will be offering comprehensive services for people prescribed OCREVUS to help minimize barriers to access and reimbursement. Patients can call 1-844-OCREVUS for more information. For people who qualify, Genentech plans to offer patient assistance programs through Genentech Access Solutions. More information is also available at (866) 4ACCESS/(866) 422-2377 or http://www.Genentech-Access.com.

The OCREVUS Marketing Authorization Application (MAA) has also been validated by the European Medicines Agency (EMA) and is currently under review.

About the OPERA I and OPERA II studies in relapsing forms of MS

OPERA I and OPERA II are Phase III, randomized, double-blind, double-dummy, global multi-center studies evaluating the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months) compared with interferon beta-1a (44 mcg administered by subcutaneous injection three times per week) in 1,656 people with relapsing forms of MS. In these studies, relapsing MS (RMS) was defined as relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with relapses.

About the ORATORIO study in primary progressive MS

ORATORIO is a Phase III, randomized, double-blind, global multi-center study evaluating the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months; given as two 300 mg infusions two weeks apart) compared with placebo in 732 people with PPMS. The blinded treatment period of the ORATORIO study continued until all patients had received at least 120 weeks of either OCREVUS or placebo and a predefined number of confirmed disability progression (CDP) events was reached overall in the study.

A summary of the data from the OPERA I, OPERA II and ORATORIO studies that support this approval is below.

Key data in RMS patients treated with OCREVUS showed:

  • A 46 percent and 47 percent relative reduction in the annualized relapse rate (ARR) compared with interferon beta-1a over the two-year period in OPERA I and OPERA II, respectively (p < 0.0001 and p < 0.0001).
  • A 40 percent relative risk reduction in confirmed disability progression (CDP) sustained for 12 weeks compared with interferon beta-1a in a pooled analysis of OPERA I and OPERA II, as measured by the Expanded Disability Status Scale (EDSS) (p=0.0006).
  • A 94 percent and 95 percent relative reduction in the total number of T1 gadolinium-enhancing lesions compared with interferon beta-1a in OPERA I and OPERA II, respectively (p < 0.0001 and p < 0.0001).
  • A 77 percent and 83 percent relative reduction in the total number of new and/or enlarging T2 lesions compared with interferon beta-1a in OPERA I and OPERA II, respectively (p < 0.0001 and p < 0.0001).

Key data in PPMS patients treated with OCREVUS showed:

  • A 24 percent relative risk reduction in CDP sustained for at least 12 weeks compared with placebo, as measured by the EDSS (p=0.0321).
  • A -0.39 cm3 mean change in volume of brain hyperintense T2 lesions compared with a 0.79 cm3 mean change in volume of placebo-treated patients over 120 weeks (p < 0.0001).
  • A 25 percent relative risk reduction in the proportion of patients with 20 percent worsening of the timed 25-foot walk confirmed at 12 weeks.

The most common side effects associated with OCREVUS in all Phase III studies were infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity. Potential serious side effects may include infusion reactions, infections and malignancies where only routine screening is required based on age and medical history. 

About multiple sclerosis

Multiple sclerosis (MS) is a chronic disease that affects an estimated 400,000 people in the U.S., for which there is currently no cure. MS occurs when the immune system abnormally attacks the insulation and support around nerve cells (myelin sheath) in the brain, spinal cord and optic nerves, causing inflammation and consequent damage. This damage can cause a wide range of symptoms, including muscle weakness, fatigue and difficulty seeing, and may eventually lead to disability. Most people with MS experience their first symptom between 20 and 40 years of age, making the disease the leading cause of non-traumatic disability in younger adults.  

Relapsing-remitting MS (RRMS) is the most common form of the disease and is characterized by episodes of new or worsening signs or symptoms (relapses) followed by periods of recovery. Approximately 85 percent of people with MS are initially diagnosed with RRMS. The majority of people who are diagnosed with RRMS will eventually transition to secondary progressive MS (SPMS), in which they experience steadily worsening disability over time. Relapsing forms of MS (RMS) include people with RRMS and people with SPMS who continue to experience relapses. Primary progressive MS (PPMS) is a debilitating form of the disease marked by steadily worsening symptoms but typically without distinct relapses or periods of remission. Approximately 15 percent of people with MS are diagnosed with the primary progressive form of the disease. Until now, there have been no FDA-approved treatments for PPMS.

People with all forms of MS experience disease activity – inflammation in the nervous system and permanent loss of nerve cells in the brain – even when their clinical symptoms aren’t apparent or don’t appear to be getting worse. An important goal of treating MS is to reduce disease activity as soon as possible to slow how quickly a person’s disability progresses. Despite available disease-modifying treatments (DMTs), some people with RMS continue to experience disease activity and disability progression.

About OCREVUS (ocrelizumab)

OCREVUS is a humanized monoclonal antibody designed to selectively target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. This nerve cell damage can lead to disability in people with MS. Based on preclinical studies, OCREVUS binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved.

OCREVUS is administered by intravenous infusion every six months. The first dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.

OCREVUS U.S. Indication

OCREVUS is a prescription medicine used to treat adults with relapsing or primary progressive forms of multiple sclerosis.

It is not known if OCREVUS is safe or effective in children.

Important Safety Information

Who should not receive OCREVUS?

Do not receive OCREVUS if you are a patient that has an active hepatitis B virus (HBV) infection. Do not receive OCREVUS if you are a patient that has had a life threatening allergic reaction to OCREVUS. Patients should tell their healthcare provider if they have had an allergic reaction to OCREVUS or any of its ingredients in the past.

What is the most important information about OCREVUS?

OCREVUS can cause serious side effects, including:

  • Infusion Reaction: OCREVUS can cause infusion reactions that can be serious and require a patient to be hospitalized. A patient will be monitored during the infusion and for at least 1 hour after each infusion of OCREVUS for signs and symptoms of an infusion reaction. Patients should tell their healthcare provider or nurse if they get any of these symptoms: itchy skin, rash, hives, tiredness, coughing or wheezing, trouble breathing, throat irritation or pain, feeling faint, fever, redness on the face (flushing), nausea, headache, swelling of the throat, dizziness, shortness of breath, fatigue, fast heart beat.

These infusion reactions can happen for up to 24 hours after the infusion. It is important that patients call their healthcare provider right away if they get any of the signs or symptoms listed above after each infusion. If a patient gets infusion reactions, the healthcare provider may need to stop or slow down the rate of the infusion.

  • Infection:
    • OCREVUS increases a patient’s risk of getting upper respiratory tract infections, lower respiratory tract infections, skin infections, and herpes infections. Patients should tell their healthcare provider if they have an infection or have any of the following signs of infection including fever, chills, a cough that does not go away, or signs of herpes (such as cold sores, shingles, or genital sores). These signs can happen during treatment or after a patient has received their last dose of OCREVUS. If a patient has an active infection, their healthcare provider should delay treatment with OCREVUS until the infection is gone.
    • Progressive Multifocal Leukoencephalopathy (PML): Although no cases have been seen with OCREVUS treatment, PML may happen with OCREVUS. PML is a rare brain infection that usually leads to death or severe disability. Patients should tell their healthcare provider right away if they have any new or worsening neurologic signs or symptoms. These may include problems with thinking, balance, eyesight, weakness on one side of the body, strength, or using arms or legs.
    • Hepatitis B virus (HBV) reactivation: Before starting treatment with OCREVUS, a patient’s healthcare provider will do blood tests to check for hepatitis B viral infection. If a patient has ever had hepatitis B virus infection, the hepatitis B virus may become active again during or after treatment with OCREVUS. Hepatitis B virus becoming active again (called reactivation) may cause serious liver problems including liver failure or death. A healthcare provider will monitor a patient if they are at risk for hepatitis B virus reactivation during treatment and after they stop receiving OCREVUS.
    • Weakened immune system: OCREVUS taken before or after other medicines that weaken the immune system could increase a patient’s risk of getting infections.

Before receiving OCREVUS, patients should tell their healthcare provider about all of their medical conditions, including if they:

  • have ever taken, take, or plan to take medicines that affect the immune system, or other treatments for MS.
  • have ever had hepatitis B or are a carrier of the hepatitis B virus.
  • have had a recent vaccination or are scheduled to receive any vaccinations. A patient should receive any required vaccines at least 6 weeks before they start treatment with OCREVUS. A patient should not receive certain vaccines (called ‘live’ or ‘live attenuated’ vaccines) while being treated with OCREVUS and until their healthcare provider tells them that their immune system is no longer weakened.
  • are pregnant, think that they might be pregnant, or plan to become pregnant. It is not known if OCREVUS will harm an unborn baby. Patients should use birth control (contraception) during treatment with OCREVUS and for 6 months after the last infusion of OCREVUS.
  • are breastfeeding or plan to breastfeed. It is not known if OCREVUS passes into the breast milk. Patients should talk to their healthcare provider about the best way to feed their baby if the patient takes OCREVUS.

What are possible side effects of OCREVUS?

OCREVUS may cause serious side effects, including:

  • Risk of cancers (malignancies) including breast cancer. Patients should follow their healthcare provider’s recommendations about standard screening guidelines for breast cancer.

Most common side effects include infusion reactions and infections.

These are not all the possible side effects of OCREVUS.

Patients should call their doctor for medical advice about side effects. Side effects may also be reported to the FDA at 1-800-FDA-1088.

For more information, go to http://www.OCREVUS.com or call 1-844-627-3887.

For additional safety information, please see the full Prescribing Information and Medication Guide.

About Genentech in neuroscience

Neuroscience is a major focus of research and development at Genentech and Roche. The company’s goal is to develop treatment options based on the biology of the nervous system to help improve the lives of people with chronic and potentially devastating diseases. Roche has more than a dozen investigational medicines in clinical development for diseases that include multiple sclerosis, Alzheimer’s disease, spinal muscular atrophy, Parkinson’s disease and autism.

About Genentech

Founded 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

 

All trademarks used or mentioned in this release are protected by law. Rebif is a registered trademark of Merck KGaA and EMD Serono, Inc.

 

###