ULTOMIRIS® (RAVULIZUMAB-CWVZ)

For intravenous use, 300 mg/30 mL vial
Ultomiris® is a treatment option for adult patients living with paroxysmal nocturnal hemoglobinuria (PNH). Ultomiris® is the first and only long-acting C5 inhibitor that provides immediate and complete inhibition for 8 weeks.

John Orloff, M.D., EVP, Head of R&D, discusses
the patient journey for people living with PNH.

ABOUT PNH

Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, debilitating and life-threatening ultra-rare blood disorder characterized by complement-mediated hemolysis (destruction of red blood cells).1,2 PNH can strike men and women of all races, backgrounds, and ages without warning, with an average age of onset in the early 30s.1,3

Patients with PNH may experience a wide range of signs and symptoms such as fatigue, difficulty swallowing (dysphagia), shortness of breath (dyspnea), abdominal pain, erectile dysfunction, dark-colored urine (hemoglobinuria), and anemia.6,7,8,9,10,11,12

The most devastating consequence of hemolysis in PNH is thrombosis (blood clotting), which can damage organs and cause premature death.13 Thrombosis can occur in blood vessels throughout the body, and the first thrombotic event can be fatal.2,3,14Additionally, patients with PNH often suffer from impaired health-related quality of life.8

INDICATION & IMPORTANT SAFETY INFORMATION FOR ULTOMIRIS

INDICATION

ULTOMIRIS® is indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH).

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS

Life-threatening meningococcal infections/sepsis have occurred in patients treated with ULTOMIRIS. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early.

  • Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies.
  • Immunize patients with meningococcal vaccines at least 2 weeks prior to administering the first dose of ULTOMIRIS, unless the risks of delaying ULTOMIRIS therapy outweigh the risk of developing a meningococcal infection [see Warnings and Precautions for additional guidance on the management of the risk of meningococcal infection].
  • Vaccination reduces, but does not eliminate, the risk of meningococcal infections. Monitor patients for early signs of meningococcal infections and evaluate immediately if infection is suspected.

ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the ULTOMIRIS REMS, prescribers must enroll in the program [see Warnings and Precautions]. Enrollment in the ULTOMIRIS REMS program and additional information are available by telephone: 1-888-765-4747 or at www.ultomirisrems.com.

CONTRAINDICATIONS

ULTOMIRIS is contraindicated in patients with unresolved Neisseria meningitidis infection.

WARNINGS AND PRECAUTIONS

Serious Meningococcal Infections

Risk and Prevention

Life-threatening meningococcal infections have occurred in patients treated with ULTOMIRIS. The use of ULTOMIRIS increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis). Meningococcal disease due to any serogroup may occur.

Vaccinate for meningococcal disease according to the most current Advisory Committee on Immunization Practices (ACIP) recommendations for patients with complement deficiencies. Revaccinate patients in accordance with ACIP recommendations considering the duration of ULTOMIRIS therapy.

Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of ULTOMIRIS. If urgent ULTOMIRIS therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide patients with 2 weeks of antibacterial drug prophylaxis.

In clinical studies, 59 patients with PNH were treated with ULTOMIRIS less than 2 weeks after meningococcal vaccination. All of these patients received antibiotics for prophylaxis of meningococcal infection until at least 2 weeks after meningococcal vaccination. The benefits and risks of antibiotic prophylaxis for prevention of meningococcal infections in patients receiving ULTOMIRIS have not been established.

Vaccination reduces, but does not eliminate, the risk of meningococcal infections. In clinical studies, 3 out of 261 PNH patients developed serious meningococcal infections/sepsis while receiving treatment with ULTOMIRIS; all 3 had been vaccinated. These 3 patients recovered while continuing treatment with ULTOMIRIS.

Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Inform patients of these signs and symptoms and steps to be taken to seek immediate medical care. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider discontinuation of ULTOMIRIS in patients who are undergoing treatment for serious meningococcal infection.

ULTOMIRIS REMS

Due to the risk of meningococcal infections, ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the ULTOMIRIS REMS, prescribers must enroll in the program.

Prescribers must counsel patients about the risk of meningococcal infection/sepsis, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccines.

Enrollment in the ULTOMIRIS REMS and additional information are available by telephone: 1-888-765-4747 or at www.ultomirisrems.com.

Other Infections

ULTOMIRIS blocks terminal complement activation; therefore patients may have increased susceptibility to encapsulated bacteria infections, especially infections caused by Neisseria meningitis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent,Neisseria gonorrhoeae. If ULTOMIRIS therapy is administered to patients with active systemic infections, monitor closely for signs and symptoms of worsening infection.

Monitoring Disease Manifestations after ULTOMIRIS Discontinuation

After discontinuing treatment with ULTOMIRIS, closely monitor for signs and symptoms of hemolysis, identified by elevated LDH along with sudden decrease in PNH clone size or hemoglobin, or re-appearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. Monitor any patient who discontinues ULTOMIRIS for at least 16 weeks to detect hemolysis and other reactions. If signs and symptoms of hemolysis occur after discontinuation, including elevated LDH, consider restarting treatment with ULTOMIRIS.

Thromboembolic Event Management

The effect of withdrawal of anticoagulant therapy during ULTOMIRIS treatment has not been established. Therefore, treatment with ULTOMIRIS should not alter anticoagulant management.

Infusion Reactions

Administration of ULTOMIRIS may result in infusion reactions. In clinical trials, 3 out of 222 patients with PNH treated with ULTOMIRIS experienced infusion reactions (lower back pain, drop in blood pressure and infusion-related pain) during ULTOMIRIS administration. These reactions did not require discontinuation of ULTOMIRIS. Interrupt ULTOMIRIS infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

Adverse Reactions

Adverse reactions reported in 5% or more of patients treated with ULTOMIRIS vs. Eculizumab was Upper respiratory tract infection (39% vs 39%), Headache (32% vs. 26%), Diarrhea (9% vs. 5%), Nausea (9% vs. 9%), Pyrexia (7% vs 8%), Pain in extremity (6% vs. 5%), Abdominal pain (6% vs. 7%), Dizziness (5% vs. 6%), Arthralgia (5% vs. 5%).

Serious adverse reactions were reported in 15 (6.8%) patients receiving ULTOMIRIS. The serious adverse reactions in patients treated with ULTOMIRIS included hyperthermia and pyrexia. No serious adverse reaction was reported in more than 1 patient treated with ULTOMIRIS.

One fatal case of sepsis was identified in a patient treated with ULTOMIRIS.

Please see full prescribing information for ULTOMIRIS, including Boxed WARNING, regarding serious and life-threatening meningococcal infections/sepsis.

References

  1. Hill A, Richards SJ, Hillmen P. Br J Haematol. 2007 May;137(3):181-92.
  2. Hillmen P, Lewis SM, Bessler M, et al. NEngl J Med. 1995 Nov 9;333(19):1253-8.
  3. Socié G, Mary JY, de Gramont A, et al. Lancet. 1996;348:573-577.
  4. Hillmen P, Muus P, Röth A, et al. Br J Haematol. 2013;162:62-73.
  5. Loschi M, Porcher R, Barraco F, et al. Am J Hematol. 2016;91:366-370.
  6. Schrezenmeier H, Muus P, Socié G, et al. Haematologica. 2014;99:922-929.
  7. Brodsky RA. Blood Rev. 2008;22:65-74.
  8. Weitz I, Meyers G, Lamy T, et al. Intern Med J. 2013;43:298-307.
  9. Lee JW, Jang JN, Kim JS, et al. Int Hematol. 2013;97:749-757.
  10. Dacie JV, Lewis SM. Paroxysmal nocturnal haemoglobinuria: clinical manifestations, haematology, and nature of the disease. Ser Haemat. 1972;5:3-23.
  11. Nishimura J, Kanakura Y, Ware RE, et al.Medicine (Baltimore) 2004 May;83(3):193-207.
  12. Parker C, Omine M, Richards S, et al. Blood. 2005 Dec 1;106(12):3699-3709.
  13. Hillmen P, Muus P, Duhrsen U, et al.Blood. 2007 Dec 1;110(12):4123-8.
  14. Hillmen P, Elebute MO, Kelly R, et al. Blood. 2007;110: Abstract 3678.
  15. Hillmen P, Elebute MO, Kelly R, et al. Am J Hematol. 2010;85:553-559.
  16. Kim JS, Jang JH, Lee JW, et al. In: Posters of the 16th Congress of the European Hematology Association; June 9-12, 2011; London, United Kingdom. Abstract 0271.

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