FDA Approves Genentech’s Enspryng for Neuromyelitis Optica Spectrum Disorder

• First and only FDA-approved subcutaneous treatment option for anti-aquaporin-4 antibody positive NMOSD that can be self-administered by a person with NMOSD or a caregiver every four weeks
• First and only approved therapy for NMOSD designed to target and inhibit interleukin-6 receptor activity, using novel recycling antibody technology
• Approval supported by one of the largest clinical trial programs undertaken for this rare disease

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has approved Enspryng^™ (satralizumab-mwge) as the first and only subcutaneous treatment for adults living with anti-aquaporin-4 (AQP4) antibody positive neuromyelitis optica spectrum disorder (NMOSD). NMOSD is a rare, lifelong and debilitating autoimmune disorder of the central nervous system, often misdiagnosed as multiple sclerosis, that primarily damages the optic nerve(s) and spinal cord, causing blindness, muscle weakness and paralysis.

“Today’s FDA approval of Enspryng, the first subcutaneous NMOSD treatment using novel recycling antibody technology, builds upon the work we’ve done in multiple sclerosis with Ocrevus to develop first-in-class medicines and further the scientific understanding of neuroimmunological diseases,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We thank the NMOSD community, including patients and investigators who participated in Enspryng clinical trials.”

Enspryng is a humanized monoclonal antibody and the only approved therapy for NMOSD designed to target and inhibit interleukin-6 (IL-6) receptor activity, believed to play a key role in the inflammation associated with NMOSD. The treatment was designed using novel recycling antibody technology, which, compared to conventional technology, allows for longer duration of antibody circulation and subcutaneous dosing every four weeks.

“For people with NMOSD, relapses can cause devastating, irreversible and disabling neurological effects,” said Professor Jeffrey Bennett, University of Colorado Neurology & Ophthalmology, and investigator for the Enspryng pivotal clinical trials. “Having an approved therapy that can be administered subcutaneously in the home and has demonstrated an impact on the frequency of relapses is an important advancement for patients.”

“We are very optimistic the addition of this new approved treatment option will make a meaningful difference for those living with NMOSD, those who love and support them and the doctors who treat them,” said Victoria Jackson, founder, The Guthy-Jackson Charitable Foundation. “When my daughter was diagnosed with NMOSD in 2008, there were no approved treatment options, and a critical lack of resources and understanding for people living with this disabling disorder. After years of dedicated effort and collaboration, the FDA approval of Enspryng exemplifies how patients, industry, and academia can find solutions together.”

Enspryng can be administered in the home by a person living with NMOSD or a caregiver following training from a healthcare provider. Enspryng treatment is administered every four weeks after an initial loading dose.

Enspryng will be available in the United States in two weeks. Genentech is committed to helping patients access the medicines prescribed by their physician. For people with NMOSD, the Enspryng Access Solutions team is available to answer questions, provide product education, injection training and help families understand insurance coverage and navigate appropriate financial assistance options to start and stay on Enspryng. Patients can call 1-844-NSPRYNG (844-677-7964) to speak to a Patient Navigator or visit http://www.Enspryng.com.

FDA approval is based on results from one of the largest pivotal clinical trial programs undertaken for this rare neurological disorder

This approval is supported by results from two randomized controlled Phase III clinical trials, the SAkuraStar and SAkuraSky studies, in which Enspryng demonstrated robust and sustained efficacy and a favorable safety profile in adults with AQP4 antibody positive NMOSD. Results were sustained for 96 weeks, significantly reducing the risk of relapse compared with placebo as a monotherapy and when used concurrently with baseline immunosuppressant therapy (IST), which has commonly been used to manage NMOSD symptoms associated with relapses.

In the SAkuraStar monotherapy study’s AQP4 antibody positive subgroup, 76.5% of Enspryng-treated patients were relapse-free at 96 weeks, compared to 41.1% with placebo. In the SAkuraSky study, which evaluated Enspryng when used concurrently with baseline IST, 91.1% of Enspryng-treated AQP4 antibody positive subgroup patients were relapse-free at 96 weeks, compared to 56.8% with placebo. The primary endpoint of both SAkuraStar and SAkuraSky was time to first protocol-defined relapse (PDR) adjudicated by an independent review committee in the double-blind period.

The most common adverse reactions with Enspryng (incidence ≥ 15%) were nasopharyngitis, headache, upper respiratory tract infection, gastritis, rash, arthralgia, extremity pain, fatigue and nausea.

About SAkuraStar and SAkuraSky in NMOSD

SAkuraStar is a Phase III multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Enspryng monotherapy administered to patients with NMOSD. The primary endpoint is the time to first protocol-defined relapse (PDR), adjudicated by an independent review committee in the double-blind period. Results from the SAkuraStar study were presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), September 11-13, 2019, and were published in the May 1, 2020 edition of The Lancet Neurology.

Ninety-five adult patients were randomized to either of the following two treatment groups in a 2:1 ratio: Enspryng (120 mg) or placebo. Both treatments were administered subcutaneously at week 0, 2, and 4. The subsequent treatment was continued at 4-week intervals. The double-blind treatment period ended at 1.5 years after the enrollment of the last patient. After experiencing a PDR or upon completion of the study, patients in both groups were offered treatment with Enspryng in an open label extension (OLE) period. Patients with aquaporin-4 (AQP4) antibody positive or negative neuromyelitis optica (NMO, as defined by the diagnostic criteria in 2006) and those with AQP4 antibody positive NMOSD were enrolled. The number of AQP4 antibody negative patients was limited to approximately 33% of the total population of the study. Data have shown that AQP4 antibody positive patients may experience a greater likelihood of relapse and poorer long-term outcomes than AQP4 antibody negative patients.

SAkuraSky is a Phase III multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Enspryng added to baseline immunosuppressant therapy in patients with NMOSD. The primary endpoint was the time to first PDR as adjudicated by an independent review committee in the double-blind period. Results from the SAkuraSky study were published in the November 28, 2019 edition of the New England Journal of Medicine (NEJM).

Seventy-six adult patients were randomized to either of the following two treatment groups in a 1:1 ratio: Enspryng (120 mg) or placebo added to baseline therapy (azathioprine, mycophenolate mofetil and/or corticosteroids). Both treatments were administered subcutaneously at week 0, 2, and 4. The subsequent treatment was continued at 4-week intervals. The double-blind treatment period ended when patients experienced a PDR; the study ended when the total number of PDRs reached 26. After experiencing a PDR or upon completion of the study, patients in both groups were offered treatment with Enspryng in an OLE period. Patients with AQP4 antibody positive or negative neuromyelitis optica (NMO, as defined by diagnostic criteria in 2006) and those with AQP4 antibody positive NMOSD were enrolled. AQP4 antibody negative patients represented approximately 30% of the SAkuraSky study population.

About neuromyelitis optica spectrum disorder (NMOSD)

NMOSD is a rare, lifelong and debilitating autoimmune condition of the central nervous system that primarily damages the optic nerve(s) and spinal cord, causing blindness, muscle weakness and paralysis. People with NMOSD experience unpredictable, severe relapses directly causing cumulative, permanent, neurological damage and disability. In some cases, relapse can result in death. NMOSD affects over 10,000 people in Europe, up to 15,000 people in the United States and approximately 200,000 people worldwide. NMOSD can affect individuals of any age, race and gender, but is most common among women in their 30s and 40s, and appears to occur at higher rates in people of African or Asian background. There is some evidence that people of African or Asian descent may also experience a more severe disease course.

NMOSD is commonly associated with pathogenic antibodies (AQP4) that target and damage a specific cell type, called astrocytes, resulting in inflammatory lesions of the optic nerve(s), spinal cord and brain. AQP4 antibodies are detectable in the blood serum of around 70-80% of NMOSD patients.

Although most cases of NMOSD can be confirmed through diagnostic tests, people living with the condition are still frequently misdiagnosed with multiple sclerosis. This is due to overlapping characteristics of the two disorders, including a higher prevalence in women, similar symptoms and the fact that both are relapse-based conditions.

About Enspryng™ (satralizumab-mwge)

Enspryng, which was designed by Chugai, a member of the Roche group, is a humanized monoclonal antibody that targets IL-6 receptor activity. The cytokine IL-6 is believed to be a key driver in NMOSD, triggering the inflammation cascade and leading to damage and disability. Enspryng was designed using novel recycling antibody technology, which compared to conventional technology, allows for longer duration of the antibody and subcutaneous dosing every four weeks.

Positive Phase III results for Enspryng, as both monotherapy and used concurrently with baseline immunosuppressant therapy, suggest that IL-6 inhibition is an effective therapeutic approach for NMOSD. The Phase III clinical development program for Enspryng includes two studies: SAkuraStar and SAkuraSky.

Enspryng is also approved in Canada, Japan and Switzerland. Applications are under review with numerous regulators, including in the European Union and China.

Enspryng has been designated as an orphan drug in the United States, Europe and Japan. In addition, it was granted Breakthrough Therapy Designation for the treatment of NMOSD by the FDA in December 2018.

What is Enspryng?

Enspryng is a prescription medicine used to treat neuromyelitis optica spectrum disorder (NMOSD) in adults who are aquaporin-4 (AQP4) antibody positive.

It is not known if Enspryng is safe and effective in children.

Important Safety Information

Patients should not take Enspryng if they:

• are allergic to satralizumab-mwge or any of the ingredients in Enspryng
• have an active hepatitis B infection
• have active or untreated inactive (latent) tuberculosis (TB)

Enspryng may cause serious side effects including:

• Infections. Enspryng can increase risk of serious infections some of which can be life-threatening. Patients should speak with their healthcare provider if they are being treated for an infection and call right away if there are signs of an infection, with or without a fever, such as:
  • chills, feeling tired, muscle aches, cough that will not go away or a sore throat
  • skin redness, swelling, tenderness, pain or sores on the body
  • diarrhea, belly pain, or feeling sick
  • burning when urinating or urinating more often than usual

• A healthcare provider will check for infection and treat it if needed before starting or continuing to take Enspryng
  • A healthcare provider should test for hepatitis and TB before initiating Enspryng
  • All required vaccinations should be completed before starting Enspryng. People using Enspryng should not be given ‘live’ or ‘live-attenuated’ vaccines. ‘Live’ or ‘live-attenuated’ vaccines should be given at least 4 weeks before a patient starts Enspryng. A healthcare provider may recommend that a patient receive a ‘non-live’ (inactivated) vaccine, such as some of the seasonal flu vaccines. If a patient plans to get a ‘non-live’ (inactivated) vaccine it should be given, whenever possible, at least 2 weeks before starting Enspryng

• Increased liver enzymes. A healthcare provider should order blood tests to check patient liver enzymes before and while taking Enspryng. A healthcare provider will dictate how often these blood tests are needed. Patients should complete all follow-up blood tests as ordered by a healthcare provider. A healthcare provider may wait to start Enspryng if liver enzymes are increased
• Low neutrophil count. Enspryng can cause a decrease in neutrophil counts in the blood. Neutrophils are white blood cells that help the body fight off bacterial infections. A healthcare provider should order blood tests to check neutrophil counts while a patient is taking Enspryng.
• Serious allergic reactions that may be life-threatening have happened with other medicines like Enspryng. Patients should call their healthcare provider right away if they have any of these symptoms of an allergic reaction:
  • shortness of breath or trouble breathing
  • swelling of lips, face, or tongue
  • dizziness or feeling faint
  • moderate or severe stomach (abdominal) pain or vomiting
  • chest pain

Before taking Enspryng, patients should tell their healthcare provider about all of their medical conditions, including if they

• have or think they have an infection
• have liver problems
• have ever had hepatitis B or are a carrier of the hepatitis B virus
• have had or have been in contact with someone with TB
• have had a recent vaccination or are scheduled to receive any vaccination
• are pregnant, think they might be pregnant, or plan to become pregnant. It is not known if Enspryng will harm one’s unborn baby
• are breastfeeding or plan to breastfeed. It is not known if Enspryng passes into breast milk. Patients should speak with their healthcare provider about the best way to feed one’s baby while on treatment with Enspryng

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins and herbal supplements

The most common side effects of Enspryng include:

• sore throat, runny nose (nasopharyngitis)
• headache
• upper respiratory tract infection
• rash
• fatigue
• nausea
• extremity pain
• inflammation of the stomach lining
• joint pain

For more information about the risks and benefit profiles of Enspryng, patients should ask their healthcare provider.

Patients may report side effects to the FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at 1-888-835-2555.

Please see the full Prescribing Information for additional Important Safety Information.

About Genentech in neuroscience

Neuroscience is a major focus of research and development at Genentech and Roche. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases.

Genentech and Roche are investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Duchenne muscular dystrophy and autism spectrum disorder. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and 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.

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