- ULTOMIRIS demonstrated consistent efficacy and safety through 52 weeks, with no cases of breakthrough hemolysis (BTH) associated with incomplete C5 complement inhibition -
- Nearly all surveyed patients preferred ULTOMIRIS over SOLIRIS® (eculizumab) -
LDH level normalization and reduction are direct markers for reduced hemolysis in PNH, a severe, ultra-rare disease characterized by complement-mediated intravascular hemolysis. PNH can cause a wide range of debilitating symptoms and complications, including thrombosis, which can occur throughout the body and result in organ damage and premature death.4,5,6,7,8,9,10,11 Incomplete inhibition of the C5 complement protein can increase the risk of BTH and related serious complications.12,13,14,15
“The confirmation of consistent efficacy and safety through 52 weeks with only six or seven infusions per year instead of 26 with SOLIRIS makes ULTOMIRIS a very compelling new therapy for patients with PNH,” said Professor
All patients in the initial ULTOMIRIS group of the extension study maintained complete C5 inhibition through 52 weeks, and no patient experienced BTH associated with incomplete C5 inhibition. All patients who had experienced incomplete C5 inhibition while receiving SOLIRIS in the first 26 weeks achieved complete C5 inhibition after the switch to ULTOMIRIS in the extension phase. No patient experienced BTH associated with incomplete C5 inhibition between weeks 27 and 52 after switching to ULTOMIRIS compared to six percent while receiving SOLIRIS in the first 26 weeks.1
“We continue to expand the body of clinical evidence supporting the potential of ULTOMIRIS to become the new standard of care for patients with PNH,” said
The most common adverse events occurred less frequently in the extension phase than during the initial treatment phase where the safety profile of ULTOMIRIS was consistent with that of SOLIRIS.2 The most common treatment-emergent adverse events in the extension phase were upper respiratory tract infection (in the initial ULTOMIRIS arm) and nasopharyngitis (in the initial SOLIRIS arm). The most frequently observed serious adverse event was pyrexia. One patient in the initial SOLIRIS arm died from lung cancer (unrelated to SOLIRIS treatment). There was no case of meningococcal infection observed.1,2
ULTOMIRIS was studied in the largest-ever Phase 3 program in PNH. The entire clinical development program for ULTOMIRIS in PNH to date represents more than 800 patient years of experience.
Additional data to be presented at the EHA congress indicate a very strong patient preference for ULTOMIRIS over SOLIRIS.3 According to results from a sub-study in the ULTOMIRIS Phase 3 extension in patients who had been stable on SOLIRIS before,16 nearly all patients (93%) preferred ULTOMIRIS due to reduced infusion frequency, ability to plan activities, overall quality of life, convenience of treatment, and effectiveness of medication until the next infusion compared to SOLIRIS.3
New results from the International PNH Registry will also be presented at the EHA congress. These data suggest that a change in clone size does not change the increased risk of major adverse vascular events in PNH,17 and that complement inhibition with SOLIRIS does not change the effectiveness of concomitant immunosuppressive therapy in patients with PNH and aplastic anemia (AA).18
One-Year Efficacy of Ravulizumab (ALXN1210) in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria Naive to Complement Inhibitors,
Patient Preferences for the Treatment of Paroxysmal Nocturnal Hemoglobinuria: Results of a
Change in Clone Size Does Not Predict Risk of Major Adverse Vascular Events: Results from the International PNH Registry,
No Change in the Effectiveness of Immunosuppressive Therapy in Patients with PNH and AA Receiving concomitant Eculizumab,
About the extension1 of the Phase 3 study in complement-naïve, adult patients with PNH2
At the end of the 26-week Phase 3 study,2 all patients (246; 125 on ULTOMIRIS, 121 on SOLIRIS) had the option to receive ULTOMIRIS every eight weeks for up to two years. The aim of this extension study is to monitor the durability of efficacy in the initial ULTOMIRIS group, the efficacy of ULTOMIRIS in the initial SOLIRIS group after the switch to ULTOMIRIS and the safety of ULTOMIRIS in all patients. A total of 243 patients (124 from the initial ULTOMIRIS group, 119 from the initial SOLIRIS group) were followed. Results for the co-primary endpoints of transfusion avoidance and LDH level normalization and the secondary endpoints of percentage change from baseline in LDH levels and proportion of patients with BTH are provided descriptively. Complete C5 inhibition was defined as plasma levels of free C5 ≤0.5 μg/ml.1
About the patient preference study3
At the end of the 26-week Phase 3 study in adult patients with PNH who had been clinically stable on SOLIRIS for at least 6 months,16 all patients (195) were given the option to continue receiving ULTOMIRIS every eight weeks for up to two years. The patient preference study enrolled patients from the extension study who had received at least two doses of ULTOMIRIS. Patient treatment preference was evaluated at one time point using an 11-item PNH-specific Patient Preference Questionnaire (PNH-PPQ©). The 11 questions included one question on overall treatment preference, nine questions on preference based on treatment characteristics, one question on the most important treatment characteristic for the overall treatment preference, four questions on aspects of treatment with SOLIRIS and four matching questions for ULTOMIRIS. Of 98 patients enrolled, 95 patients from eight countries (
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, debilitating and life-threatening ultra-rare blood disorder characterized by intravascular hemolysis (destruction of red blood cells) that is mediated by an uncontrolled activation of the complement system, a part of the immune system.4,5,19 PNH can strike men and women of all races, backgrounds and ages without warning, with an average age of onset in the early 30s.4,20 PNH often goes unrecognized, with delays in diagnosis ranging from one to more than five years.21 Patients with PNH may experience a wide range of signs and symptoms, such as fatigue, difficulty swallowing, shortness of breath, abdominal pain, erectile dysfunction, dark-colored urine and anemia.6,7,8,9,10,11,19 The most devastating consequence of chronic intravascular hemolysis is thrombosis, which can occur in blood vessels throughout the body, damage vital organs and cause premature death.22 The first thrombotic event can be fatal.4,20,23 Despite historical supportive care, including transfusion and anticoagulation management, 20 to 35 percent of patients with PNH die within five to 10 years of diagnosis.24,25 Patients with certain types of hemolytic anemia, bone marrow disorders and unexplained venous or arterial thrombosis are at increased risk of PNH.14,19,26,27,28,29
ULTOMIRIS (ravulizumab-cwvz), the first and only long-acting C5 inhibitor administered every eight weeks, is approved in the U.S. as a treatment for adults with paroxysmal nocturnal hemoglobinuria (PNH). ULTOMIRIS works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. The terminal complement cascade, when activated in an uncontrolled manner, plays a role in severe ultra-rare disorders like PNH, atypical hemolytic uremic syndrome (aHUS), anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG) and anti-aquaporin-4 (AQP4) auto-antibody-positive neuromyelitis optica spectrum disorder (NMOSD). Regulatory authorities in the
The Phase 3 study of ULTOMIRIS, administered intravenously every eight weeks in adult patients with aHUS, met its primary objective. Alexion has submitted a supplemental Biologics License Application (sBLA) to the
ULTOMIRIS has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S. and
U.S. Indication of ULTOMIRIS®
ULTOMIRIS (ravulizumab-cwvz) is a prescription medicine called a monoclonal antibody. ULTOMIRIS is used to treat adults with a disease called paroxysmal nocturnal hemoglobinuria (PNH). It is not known if ULTOMIRIS is safe and effective in children.
U.S. Important Safety Information for ULTOMIRIS®
ULTOMIRIS (ravulizumab-cwvz) is a medicine that affects the immune system. ULTOMIRIS can lower the ability of the immune system to fight infections. ULTOMIRIS increases the chance of getting serious and life-threatening meningococcal infections. Meningococcal infections may quickly become life-threatening and cause death if not recognized and treated early.
Meningococcal vaccines must be received at least 2 weeks before the first dose of ULTOMIRIS if one has not already had this vaccine. If one’s doctor decided that urgent treatment with ULTOMIRIS is needed, meningococcal vaccination should be administered as soon as possible. If one has not been vaccinated and ULTOMIRIS therapy must be initiated immediately, 2 weeks of antibiotics should also be administered with the vaccinations. If one had a meningococcal vaccine in the past, additional vaccination might be needed before starting ULTOMIRIS. Call one’s doctor or get emergency medical care right away if any of these signs and symptoms of a meningococcal infection occur: headache with nausea or vomiting, headache with a stiff neck or stiff back, fever and a rash, muscle aches with flu-like symptoms, headache and fever, fever, confusion, and eyes sensitive to light.
ULTOMIRIS is only available through a program called the ULTOMIRIS REMS.
ULTOMIRIS may also increase the risk of other types of serious infections. People who take ULTOMIRIS may have an increased risk of getting infections caused by Streptococcus pneumoniae and Haemophilus influenzae. Certain people may also have an increased risk of gonorrhea infection. To find out if one is at risk for gonorrhea infection, about gonorrhea prevention, and regular testing, talk to the healthcare provider. Call the healthcare provider right away if one has any new signs or symptoms of infection.
Before one receives ULTOMIRIS, tell the doctor about all of the medical conditions, including if one: has an infection or fever, is pregnant or plans to become pregnant, and is breastfeeding or plans to breastfeed. It is not known if ULTOMIRIS will harm an unborn baby. It is not known if ULTOMIRIS passes into the breast milk. One should not breast feed during treatment and for 8 months after one’s final dose of ULTOMIRIS.
Tell the doctor about all the medicines one takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. ULTOMIRIS and other medicines can affect each other causing side effects. Know the medications one takes and the vaccines one receives. Keep a list of them to show the doctor and pharmacist when one gets a new medicine.
If one stops receiving ULTOMIRIS, the doctor will need to monitor closely for at least 16 weeks after one stops ULTOMIRIS. Stopping ULTOMIRIS may cause breakdown of the red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include: drop in the number of the red blood cell count, tiredness, blood in the urine, stomach-area (abdomen) pain, blood clots, shortness of breath, trouble swallowing, and erectile dysfunction (ED) in males.
ULTOMIRIS can cause serious side effects including infusion reactions. Infusion reactions may happen during one’s ULTOMIRIS infusion. Symptoms of an infusion reaction with ULTOMIRIS may include lower back pain, pain with the infusion, or feeling faint. Tell the doctor or nurse right away if these symptoms develop, or any other symptoms during the ULTOMIRIS infusion that may mean one is having a serious infusion reaction, including: chest pain, trouble breathing or shortness of breath, swelling of the face, tongue, or throat, and feel faint or pass out. One’s doctor will treat the symptoms as needed. The most common side effects of ULTOMIRIS are upper respiratory infection and headache.
For more information, please see the full U.S. Prescribing Information and Medication Guide for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis, also available at: www.ultomiris.com.
U.S. Indication for SOLIRIS®
SOLIRIS (eculizumab) is a prescription medicine called a monoclonal antibody. SOLIRIS is used to treat patients with a disease called Paroxysmal Nocturnal Hemoglobinuria (PNH), adults and children with a disease called atypical Hemolytic Uremic Syndrome (aHUS) (SOLIRIS is not for use in treating people with Shiga toxin E. coli related hemolytic uremic syndrome [STEC-HUS]), and adults with a disease called generalized Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AchR) antibody positive. It is not known if SOLIRIS is safe and effective in children with PNH or gMG.
U.S. Important Safety Information for SOLIRIS®
SOLIRIS (eculizumab) is a medicine that affects the immune system. SOLIRIS can lower the ability of the immune system to fight infections. SOLIRIS increases the chance of getting serious and life-threatening meningococcal infections. Meningococcal infections may quickly become life-threatening and cause death if not recognized and treated early.
Meningococcal vaccines must be received at least 2 weeks before the first dose of SOLIRIS if one has not already had this vaccine. If one’s doctor decided that urgent treatment with SOLIRIS is needed, meningococcal vaccination should be administered as soon as possible. If one has not been vaccinated and SOLIRIS therapy must be initiated immediately, 2 weeks of antibiotics should also be administered with the vaccinations. If one had a meningococcal vaccine in the past, additional vaccination might be needed before starting SOLIRIS. Call one’s doctor or get emergency medical care right away if any of these signs and symptoms of a meningococcal infection occur: 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.
SOLIRIS is only available through a program called the SOLIRIS REMS.
SOLIRIS may also increase the risk of other types of serious infections. If one’s child is treated with SOLIRIS, make sure that the child receives vaccinations against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Certain people may be at risk of serious infections with gonorrhea. Talk to the doctor about whether one is at risk for gonorrhea infection, about gonorrhea prevention, and regular testing. Certain fungal infections (Aspergillus) may also happen if one takes SOLIRIS and has a weak immune system or a low white blood cell count.
Before one receives SOLIRIS, tell the doctor about all of the medical conditions, including if one: has an infection or fever, is pregnant or plans to become pregnant, and is breastfeeding or plans to breastfeed. It is not known if SOLIRIS will harm an unborn baby. It is not known if SOLIRIS passes into the breast milk.
Tell the doctor about all the medicines one takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements. SOLIRIS and other medicines can affect each other causing side effects.
It is important that one: has all recommended vaccinations before starting SOLIRIS, receives 2 weeks of antibiotics if one immediately starts SOLIRIS, and stays up-to-date with all recommended vaccinations during treatment with SOLIRIS. Know the medications one takes and the vaccines one receives. Keep a list of them to show the doctor and pharmacist when one gets a new medicine.
If one has PNH, the doctor will need to monitor closely for at least 8 weeks after stopping SOLIRIS. Stopping treatment with SOLIRIS may cause breakdown of the red blood cells due to PNH. Symptoms or problems that can happen due to red blood cell breakdown include: drop in the number of the red blood cell count, drop in the platelet counts, confusion, kidney problems, blood clots, difficulty breathing, and chest pain.
If one has aHUS, the doctor will need to monitor closely for at least 12 weeks after stopping SOLIRIS for signs of worsening aHUS symptoms or problems related to abnormal clotting (thrombotic microangiopathy). Symptoms or problems that can happen with abnormal clotting may include: stroke, confusion, seizure, chest pain (angina), difficulty breathing, kidney problems, swellings in arms or legs and a drop in platelet count.
SOLIRIS can cause serious side effects including serious allergic reactions. Serious allergic reactions can happen during one’s SOLIRIS infusion. Tell the doctor or nurse right away if one gets any of these symptoms during the SOLIRIS infusion: chest pain, trouble breathing or shortness of breath, swelling of the face, tongue, or throat, and feeling faint or pass out. If one has an allergic reaction to SOLIRIS, the doctor may need to infuse SOLIRIS more slowly, or stop SOLIRIS. The most common side effects in people with PNH treated with SOLIRIS include: headache, pain or swelling of the nose or throat (nasopharyngitis), back pain, and nausea. The most common side effects in people with aHUS treated with SOLIRIS include: headache, diarrhea, high blood pressure (hypertension), common cold (upper respiratory infection), stomach-area (abdominal pain), vomiting, pain or swelling of the nose or throat (nasopharyngitis), low red blood cell count (anemia), cough, swelling of legs or feet (peripheral edema), nausea, urinary tract infections, and fever. The most common side effects in people with gMG treated with SOLIRIS include: muscle and joint (musculoskeletal) pain.
Please see the accompanying full U.S. Prescribing Information and Medication Guide for SOLIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections, also available at: www.soliris.net.
Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases through the discovery, development and commercialization of life-changing therapies. As the global leader in complement biology and inhibition for more than 20 years, Alexion has developed and commercializes two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) as well as the first and only approved complement inhibitor to treat atypical hemolytic uremic syndrome (aHUS) and anti-acetylcholine receptor (AchR) antibody-positive generalized myasthenia gravis (gMG), and is also developing it for patients with neuromyelitis optica spectrum disorder (NMOSD). Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D). In addition, the company is developing several mid-to-late-stage therapies, including a second complement inhibitor, a copper-binding agent for Wilson disease and an anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G (IgG)-mediated diseases as well as several early-stage therapies, including one for light chain (AL) amyloidosis and a second anti-FcRn therapy. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, and metabolic disorders. Alexion has been named to the
This press release contains forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Alexion, including statements related to: the efficacy and safety of ULTOMIRIS as a treatment of PNH; that the Phase 3 extension study data confirm consistent efficacy and safety of ULTOMIRIS; that six or seven infusions per year instead of 26 with SOLIRIS make ULTOMIRIS a very compelling new therapy for patients with PNH; that patients prefer ULTOMIRIS over SOLIRIS and that ULTOMIRIS results in a reduced treatment burden for patients as compared to SOLIRIS; ULTOMIRIS has the potential to become the new standard of care for patients with PNH; the expected timing of the final decision of the EC with respect to pharmaceutical product approval including ULTOMIRIS for PNH; Alexion’s future plans for submitting supplemental Biologics License Application and similar applications to the applicable regulatory authorities for ULTOMIRIS as a therapy for certain indications; ULTOMIRIS is a potential treatment for patients with gMG and NMOSD; the company is planning to initiate a Phase 3 clinical trial in patients with NMOSD; the anticipated timing of the review and decision of regulatory agencies with respect to the potential approval of ULTOMIRIS as a treatment for PNH in certain jurisdictions; future plans for the evaluation and clinical trials of ULTOMIRIS in additional indications and patient populations, including subcutaneous administration; and the potential medical benefits of ULTOMIRIS for the treatment of PNH and other diseases. Forward-looking statements are subject to factors that may cause Alexion's results and plans to differ materially from those expected by these forward-looking statements, including for example: our inability to facilitate the timely conversion of patients with PNH (and any future indications) from SOLIRIS to ULTOMIRIS; payer, physician and patient acceptance of ULTOMIRIS as an alternative to SOLIRIS; ULTOMIRIS does not gain market acceptance and/or does not become the standard of care for patients with PNH and/or is not recognized by patients and physicians as the standard of care for patients with PNH; the benefits (including safety and efficacy) of ULTOMIRIS evidenced in clinical trials are not witnessed in a broader patient population; any potential post-approval restrictions that the
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Alexion Pharmaceuticals, Inc.
Arne Naeveke, PhD, +1 857-338-8597
Lauren Cettier, +41 44 457 4323
Susan Altschuller, PhD, +1 857-338-8788