– Study met primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26 –
– ULTOMIRIS demonstrated compelling efficacy as early as Week 1, sustained for 52 weeks –
“The treatment landscape for people living with gMG has advanced and expanded rapidly in recent years, empowering both patients and caregivers. However, as a clinician and scientist, I know the work is not done,” said Professor
“The approval of SOLIRIS was a critically important first step in addressing the urgent need for a treatment for people with severe symptoms and complications of MG, and was the first new treatment for this devastating disease in more than 60 years. Today’s results demonstrate that ULTOMIRIS may help a broader range of patients than was studied in the SOLIRIS Phase 3 trial, including those with milder symptoms or earlier in their treatment journey, while still offering clinically meaningful benefits that were seen as early as Week 1 and maintained up to 52 weeks,” said
About the Phase 3 Study
This global Phase 3 randomized, double-blind, placebo-controlled, multicenter 26-week study evaluated the safety and efficacy of ULTOMIRIS in adults with gMG who were not previously treated with a complement inhibitor medicine. The study enrolled 175 patients across
Patients were randomized 1:1 to receive ULTOMIRIS or placebo for a total of 26 weeks. Patients received a single weight-based loading dose on Day 1, followed by regular weight-based maintenance dosing beginning on Day 15, every 8 weeks. The primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26 was assessed along with multiple secondary endpoints evaluating improvement in disease-related and quality of life measures.
The study met its primary endpoint, with a statistically significant change in MG-ADL score from baseline through Week 26 for patients receiving ULTOMIRIS compared to those receiving placebo (ULTOMIRIS: -3.1, placebo: -1.4, treatment difference: -1.6, p<0.001).
In the prospectively-defined secondary endpoints of change from baseline through Week 26 in Quantitative Myasthenia Gravis (QMG) total score – a physician-administered assessment of MG clinical severity – as well as the proportion of patients who achieved an improvement of at least 5 points in QMG, ULTOMIRIS also demonstrated clinically meaningful and statistically significant improvements (p<0.001 and p=0.005, respectively). Nearly three times as many patients receiving ULTOMIRIS experienced an improvement of at least 5 points in their QMG score compared to patients receiving placebo (30.0% vs 11.3%). These improvements in MG-ADL and QMG scores were observed as early as Week 1 and were sustained through Week 26.
Additional secondary endpoints assessing qualify of life measures, such as Revised 15-Component Myasthenia Gravis Quality of Life (MG-QOL15r) score (p=0.064) and Neuro-QOL Fatigue score (p=0.373), did not meet statistical significance at Week 26. The proportion of patients who achieved an improvement of at least 3 points in MG-ADL score (ULTOMIRIS: 56.7%, placebo: 34.1%, nominal p=0.005), was not considered statistically significant based on hierarchical testing.
During the randomized controlled period, adverse events were comparable between the ULTOMIRIS and placebo groups. The most frequently observed adverse events were headache (ULTOMIRIS: 18.6%; placebo: 25.8%), diarrhea (ULTOMIRIS: 15.1%; placebo: 12.4%) and nausea (ULTOMIRIS: 10.5%; placebo: 10.1%). The most frequently observed serious adverse events were MG crisis (ULTOMIRIS: 1.2%) and MG worsening (placebo: 3.4%).
Through 52 weeks (26 weeks randomized controlled period + 26 weeks of open-label extension), there were four patient deaths in the ULTOMIRIS group – three of them were due to COVID-19 and none were considered related to treatment with ULTOMIRIS. No cases of meningococcal infection were observed through 52 weeks.
Patients who completed the randomized controlled period were eligible to continue into an open-label extension period evaluating the safety and efficacy of ULTOMIRIS for up to two years, which is ongoing. At the time of this preliminary analysis of the open-label extension period, 75 patients had completed 26 weeks of treatment, for a total of 52 weeks of treatment. Among the patients who received ULTOMIRIS in the randomized controlled period, the treatment effects were maintained through an additional 26 weeks of treatment, demonstrating sustained efficacy for a total of 52 weeks. In addition, patients who received placebo in the randomized controlled period and switched to ULTOMIRIS at the beginning of the open-label extension showed immediate and sustained improvement in MG-ADL and QMG scores in a similar magnitude and time course to that observed in the ULTOMIRIS group during the randomized controlled period.
About Generalized Myasthenia Gravis
Generalized myasthenia gravis (gMG) is a rare autoimmune disorder characterized by severe muscle weakness. In gMG, inflammation causes damage at the connection point between nerve cells and the muscles they control (known as the neuromuscular junction or NMJ). This damage leads to a breakdown of communication between the brain and muscles, causing loss of muscle function and severe weakness.
About 85 percent of people with gMG produce specific antibodies that bind to the surface of the cells at the NMJ. This binding activates the complement cascade and causes the immune system to attack the NMJ. People with gMG can suffer from initial symptoms, such as slurred speech, droopy eyelids, double vision, and lack of balance, which can often lead to more severe symptoms like choking, impaired swallowing, extreme fatigue and even episodes of respiratory failure.
gMG can occur at any age, but it most commonly begins for women before the age of 40 and for men after the age of 60. The prevalence of gMG is estimated at 107 to 278 per million people.
ULTOMIRIS® (ravulizumab) is the first and only long-acting C5 complement inhibitor. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. ULTOMIRIS is administered intravenously every eight weeks or, for pediatric patients less than 20 kg, every four weeks, following a loading dose. ULTOMIRIS is approved in
INDICATIONS & IMPORTANT SAFETY INFORMATION for ULTOMIRIS® (ravulizumab-cwvz)
What is ULTOMIRIS?
ULTOMIRIS is a prescription medicine used to treat:
- adults and children 1 month of age and older with a disease called Paroxysmal Nocturnal Hemoglobinuria (PNH).
- adults and children 1 month of age and older with a disease called atypical Hemolytic Uremic Syndrome (aHUS). ULTOMIRIS is not used in treating people with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).
It is not known if ULTOMIRIS is safe and effective in children younger than 1 month of age.
IMPORTANT SAFETY INFORMATION
What is the most important information I should know about ULTOMIRIS?
ULTOMIRIS is a medicine that affects your immune system and can lower the ability of your immune system to fight infections.
- ULTOMIRIS increases your chance of getting serious and life-threatening meningococcal infections that may quickly become life-threatening and cause death if not recognized and treated early.
- You must receive meningococcal vaccines at least 2 weeks before your first dose of ULTOMIRIS if you are not vaccinated.
- If your doctor decided that urgent treatment with ULTOMIRIS is needed, you should receive meningococcal vaccination as soon as possible.
- If you have not been vaccinated and ULTOMIRIS therapy must be initiated immediately, you should also receive 2 weeks of antibiotics with your vaccinations.
- If you had a meningococcal vaccine in the past, you might need additional vaccination. Your doctor will decide if you need additional vaccination.
- Meningococcal vaccines reduce but do not prevent all meningococcal infections. Call your doctor or get emergency medical care right away if you get any of these signs and symptoms of a meningococcal infection: headache with nausea or vomiting, headache and fever, headache with a stiff neck or stiff back, fever, fever and a rash, confusion, muscle aches with flu-like symptoms and eyes sensitive to light.
Your doctor will give you a Patient Safety Card about the risk of meningococcal infection. Carry it with you at all times during treatment and for 8 months after your last ULTOMIRIS dose. It is important to show this card to any doctor or nurse to help them diagnose and treat you quickly.
ULTOMIRIS is only available through a program called the ULTOMIRIS REMS. Before you can receive ULTOMIRIS, your doctor must: enroll in the ULTOMIRIS REMS program; counsel you about the risk of meningococcal infection; give you information and a Patient Safety Card about the symptoms and your risk of meningococcal infection (as discussed above); and make sure that you are vaccinated with a meningococcal vaccine, and if needed, get revaccinated with the meningococcal vaccine. Ask your doctor if you are not sure if you need to be revaccinated.
ULTOMIRIS may also increase the risk of other types of serious infections. Make sure your child receives vaccinations against Streptococcus pneumoniae and Haemophilis influenzae type b (Hib) if treated with ULTOMIRIS. Call your doctor right away if you have any new signs or symptoms of infection.
Who should not receive ULTOMIRIS?
Do not receive ULTOMIRIS if you have a meningococcal infection or have not been vaccinated against meningococcal infection unless your doctor decides that urgent treatment with ULTOMIRIS is needed.
Before you receive ULTOMIRIS, tell your doctor about all of your medical conditions, including if you: have an infection or fever, are pregnant or plan to become pregnant, and are breastfeeding or plan to breastfeed. It is not known if ULTOMIRIS will harm your unborn baby or if it passes into your breast milk. You should not breastfeed during treatment and for 8 months after your final dose of ULTOMIRIS.
Tell your doctor about all the vaccines you receive and medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements which could affect your treatment.
If you have PNH and you stop receiving ULTOMIRIS, your doctor will need to monitor you closely for at least 16 weeks after you stop ULTOMIRIS. Stopping ULTOMIRIS may cause breakdown of your red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include: drop in your red blood cell count, tiredness, blood in your urine, stomach-area (abdomen) pain, shortness of breath, blood clots, trouble swallowing, and erectile dysfunction (ED) in males.
If you have aHUS, your doctor will need to monitor you closely for at least 12 months after stopping treatment for signs of worsening aHUS or problems related to a type of abnormal clotting and breakdown of your red blood cells called thrombotic microangiopathy (TMA). Symptoms or problems that can happen with TMA may include: confusion or loss of consciousness, seizures, chest pain (angina), difficulty breathing and blood clots or stroke.
What are the possible side effects of ULTOMIRIS?
ULTOMIRIS can cause serious side effects including infusion-related reactions. Symptoms of an infusion-related reaction with ULTOMIRIS may include lower back pain, feeling faint or discomfort in your arms or legs. Tell your doctor or nurse right away if you develop these symptoms, or any other symptoms during your ULTOMIRIS infusion that may mean you are having a serious infusion reaction, including: chest pain, trouble breathing or shortness of breath, swelling of your face, tongue, or throat, and feel faint or pass out.
The most common side effects of ULTOMIRIS in people treated for PNH are upper respiratory tract infection and headache.
The most common side effects of ULTOMIRIS in people with aHUS are upper respiratory tract infection, diarrhea, nausea, vomiting, headache, high blood pressure and fever.
Tell your doctor about any side effect that bothers you or that does not go away. These are not all the possible side effects of ULTOMIRIS. For more information, ask your doctor or pharmacist. Call your doctor right away if you miss an ULTOMIRIS infusion or for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Please see the accompanying full Prescribing Information and Medication Guide for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis.
This press release contains forward-looking statements that involve risks and uncertainties relating to future events and the future performance of
Forward-looking statements are subject to factors that may cause
Senior Director, Corporate Communications
Kevin O’Neil, (857) 338-8505
Associate Director, Investor Relations