Important information regarding COVID-19 and access to medicine
Alexion understands our patients and healthcare providers may be concerned about the evolving COVID-19 situation and our products.
ULTOMIRIS, built on the foundation of eculizumab, has a ~4x longer terminal half-life.1-3
ULTOMIRIS is administered up to every 8 weeks.* The less frequent infusions and visits to hospitals/clinics associated with ULTOMIRIS vs eculizumab can potentially reduce exposure of paroxysmal nocturnal hemoglobinuria (PNH) patients, caregivers, and healthcare staff to high-risk environments by enabling social distancing.1,2
For most patients, the cost of medicine associated with ULTOMIRIS will be less than the costs of eculizumab on an ongoing, annual basis.4**
Infusion-Related Reactions
Administration of ULTOMIRIS may result in infusion-related reactions. In clinical trials, 4 out of 309 patients treated with ULTOMIRIS experienced infusion-related reactions (lower back pain, drop in blood pressure, elevation in blood pressure and limb discomfort) during ULTOMIRIS administration which did not require discontinuation. Interrupt infusion and institute supportive measures if signs of cardiovascular instability or respiratory compromise occur.
In the current COVID-19 pandemic, the American Society of Hematology (ASH) recommends that patients with PNH who require anti-complement therapy should stay on it because of the risk of serious and irreversible thrombosis. ULTOMIRIS, requiring administration every 4 or 8 weeks (depending on body weight) may be preferable over eculizumab to minimize visits to a physician’s office or infusion center.5
Based on Alexion’s understanding of the mechanism of action for ULTOMIRIS, and the extensive postmarketing experience (cumulatively, over 10 years of commercial distribution, and over 55,000 patient-years of exposure), it does not appear that patients treated with ULTOMIRIS are at higher risk of developing coronaviral infections or that the course of their infection will be different than in patients who have not received ULTOMIRIS.1,2,6
Viral respiratory infections were observed in the Alexion-sponsored clinical trials for ULTOMIRIS.1,2 Those viral respiratory infections were the same type of respiratory viral infections that are typically seen in the general population, like the common cold. In the trials, the viral respiratory infections were not serious in nature and all resolved without the patient having to discontinue treatment with ULTOMIRIS.1,2,6
Infection has been shown to amplify complement activity, which could have the potential to exacerbate a patient’s underlying condition in a complement-mediated disease.7-10 It is also important to note that Soliris and ULTOMIRIS patients are at increased risk for developing meningococcal infections, which have some of the same early symptoms as COVID-19.1,2 While meningococcal infection could present as classic meningitis with fever, headache and neck stiffness, please note the presentation can also present as meningococcal sepsis without meningitis.6
Patients should be reminded that if they develop a headache and fever or have muscle aches with flu-like symptoms (or any symptoms as described on the “Patient Safety Card”), they should call their doctor right away or seek emergency medical treatment, as these could be signs of a meningococcal infection that requires immediate medical attention. If patients cannot reach their doctor, immediately seek emergency medical treatment and show “Patient Safety Card” to emergency staff at the hospital.
Vaccination against Neisseria meningitidis is required before starting ULTOMIRIS therapy.1,2 Please refer to the latest ACIP guidelines for updated vaccine recommendations.
We made the decision to move our US teams to full-time, remote work, with the exception of essential manufacturing and research teams. While you will not see your account manager or medical science liaison at the office or in the hospital, know that we are a phone or video call away to support you and the people living with rare diseases who rely on our medicines. Your primary contact at Alexion will be in touch to ensure we know what you need, how we can help, and any preferences you may have as it relates to contact from us during this difficult time.
*Starting 2 weeks after the loading dose, maintenance doses are administered once every 4 or 8 weeks (depending on body weight).
**The average annual cost of ongoing ULTOMIRIS treatment for atypical-HUS is at least 22% less than for Soliris treatment. For PNH, the average annual cost of ULTOMIRIS treatment is 10% less than for Soliris treatment. These figures are based on average wholesale acquisition cost (WAC) for patients ≥ 40 kg. Actual costs for individual patients will vary.
- ULTOMIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.; 2021.
- SOLIRIS [prescribing information]. Boston, MA: Alexion Pharmaceuticals, Inc.; November 2020.
- Sheridan D, et al. PLoS One. 2018;13(4):e0195909.
- Levy AR, et al. Value in Health. 2019;22(suppl 2)S377.
- https://www.hematology.org/covid-19/covid-19-and-aplastic-anemia
- Data on file. Alexion Pharmaceuticals, Inc.; 2019.
- Olie KH et al. Am J Kidney Dis. 2005;45(1):e12-e15.
- Berner R et al. Pediatric Nephrology. 2002;17(3):190-192.
- Brodsky RA et al. Haematologica. E-pub ahead of print, Jan 16, 2020.
- Ueda T et al. Journal of Nippon Medical School. 2013;80(2):155-159.
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.
Because of the risk of serious meningococcal infections, ULTOMIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ULTOMIRIS REMS.
CONTRAINDICATIONS
- Patients with unresolved Neisseria meningitidis infection.
- Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying ULTOMIRIS treatment outweigh the risks of developing a meningococcal infection.
WARNINGS AND PRECAUTIONS
Serious Meningococcal Infections
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 or revaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Immunize patients without history of meningococcal vaccination at least 2 weeks prior to the first dose of ULTOMIRIS. Patients who initiate ULTOMIRIS treatment less than 2 weeks after receiving meningococcal vaccine(s) must receive appropriate prophylactic antibiotics until 2 weeks after vaccination.
In clinical studies, 59 adult 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. In clinical studies with ULTOMIRIS, <1% of patients developed serious meningococcal infections/sepsis while receiving treatment with ULTOMIRIS. All were adult patients with PNH who had been vaccinated. These patients recovered while continuing treatment with ULTOMIRIS. 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 REMS called ULTOMIRIS 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.
Additional information on the REMS requirements is available at www.ultomirisrems.com or 1-888-765-4747.
Other Infections
Patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Children treated with ULTOMIRIS may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Administer vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP guidelines. If ULTOMIRIS is administered to patients with active systemic infections, monitor closely for 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 treatment with ULTOMIRIS has not been established. Treatment should not alter anticoagulant management.
Infusion-Related Reactions
Intravenous or subcutaneous administration of ULTOMIRIS may result in systemic infusion-related reactions, including anaphylaxis and hypersensitivity reactions. In clinical trials, infusion-related reactions occurred in approximately 1% of patients treated with ULTOMIRIS. These events included lower back pain, drop in blood pressure, elevation in blood pressure, limb discomfort, drug hypersensitivity (allergic reaction), dysgeusia (bad taste), and drowsiness. These reactions did not require discontinuation of ULTOMIRIS. If signs of cardiovascular instability or respiratory compromise occur, interrupt ULTOMIRIS infusion and institute appropriate supportive measures.
Injection Site Reactions-Subcutaneous administration
27% (23/84) of patients treated with subcutaneous administration of ULTOMIRIS experienced injection site reactions which included application site rash, device allergy, infusion site pain, infusion site reaction, injection site bruising, injection site erythema, injection site hematoma, injection site induration, injection site inflammation, injection site pain, injection site pruritus, injection site rash, injection site reaction, injection site swelling, injection site urticaria, medical device site bruise, medical device site erythema, medical device site hematoma, medical device site induration, medical device site pruritus, medical device site rash, and medical device site reaction.
Allergies to Acrylic Adhesives
The on-body injector of ULTOMIRIS uses acrylic adhesive. For patients with a known allergy to acrylic adhesive, use of this product may result in an allergic reaction. Premedication can be considered, and supportive measures should be instituted if signs of allergy appear.
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. In clinical studies, clinically relevant adverse reactions in 1% of adult patients include infusion-related reactions.
Adverse reactions reported in 10% or more of pediatric patients treated with ULTOMIRIS who were treatment-naïve vs. Eculizumab-experienced was Anemia (20% vs. 25%), Abdominal pain (0% vs. 38%), Constipation (0% vs. 25%), Pyrexia (20% vs. 13%), Upper respiratory tract infection (20% vs. 75%), Pain in extremity (0% vs. 25%), Headache (20% vs. 25%).
Adverse Reactions for Subcutaneous Administration of ULTOMIRIS
Most common adverse reactions (≥10%) with ULTOMIRIS subcutaneous administration via On Body Injector in adult patients with PNH were local injection site reactions, diarrhea, and headache.
DRUG INTERACTIONS
Plasma Exchange, Plasmapheresis, and Intravenous Immunoglobulins
Concomitant use of ULTOMIRIS with plasma exchange (PE), plasmapheresis (PP), or intravenous immunoglobulin (IVIg) treatment can reduce serum ravulizumab concentrations and requires a supplemental dose of ULTOMIRIS.
Neonatal Fc Receptor Blockers
Concomitant use of ULTOMIRIS with neonatal Fc receptor (FcRn) blockers (e.g., efgartigimod) may lower systemic exposures and reduce effectiveness of ULTOMIRIS. Closely monitor for reduced effectiveness of ULTOMIRIS.
INDICATION
ULTOMIRIS is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).
Subcutaneous Use in Adult Patients with PNH
Subcutaneous administration of ULTOMIRIS is not approved for use in pediatric patients.
Please see accompanying full Prescribing Information for ULTOMIRIS, including Boxed WARNING regarding serious and life-threatening meningococcal infections/sepsis.