Exploratory Efficacy Analyses in REGAIN and the Open-label Extension Study

Exacerbation, hospitalization, and rescue therapy rates observed in REGAIN1

Placebo (n=63) SOLIRIS (n=62)
Exacerbations
10% of SOLIRIS-treated patients reported experiencing disease exacerbation compared to 24% in the placebo arm
HOSPITALIZATIONS
15% of SOLIRIS-treated patients were hospitalized compared to 29% in the placebo arm

Rescue therapy use
10% of SOLIRIS-treated patients required rescue therapies compared to 19% in the placebo arm

REGAIN Study Limitation

These observations from the REGAIN study are based on an exploratory analysis and are not intended to establish conclusions of benefit.

SELECT IMPORTANT SAFETY INFORMATION
Adverse Reactions

The most frequently reported adverse reaction in the gMG placebo-controlled clinical trial (≥10%) is: musculoskeletal pain.

Please see additional Important Safety Information for SOLIRIS, including Boxed WARNING regarding serious meningococcal infections, below.

Exacerbation, hospitalization, and rescue therapy rates in patients taking SOLIRIS for up to 3 years in the OLE study2

Pre-study (n=125) SOLIRIS (n=117)
Exacerbations
12 months before REGAIN (Pre-study): 102.4 exacerbations per 100 patient-years (136 events/124.8 patient-years)
OLE: 25.4 exacerbations per 100 patient-years (59 events/227.0 patient-years)
Pre-study (n=125) SOLIRIS (n=117)
HOSPITALIZATIONS
12 months before REGAIN (Pre-study): 81.3 hospitalizations per 100 patient-years (107 events/124.8 patient-years)
OLE: 13.7 hospitalizations per 100 patient-years (31 events/227.0 patient-years)
Pre-study (n=125) SOLIRIS (n=117)
Rescue therapy use
12 months before REGAIN (Pre-study): 67.5 rescue therapy events per 100 patient-years (24 events/31.1 patient-years)
OLE: 23.1 rescue therapy events per 100 patient-years (53 events/227.0 patient-years)
REGAIN OLE Study Limitation

These observations from the REGAIN OLE study are based on an exploratory analysis with a primary goal of evaluating safety. Any inference of efficacy or clinical significance should be interpreted with caution.

REGAIN OLE SELECT SAFETY OBSERVATIONS

Adverse events in the open-label extension study were consistent with REGAIN for up to 3 years. Infections were the most commonly reported adverse events of special interest. The most common serious AE was MG worsening (12.8%}. There was 1 nonfatal case of meningococcal infection that was reported after data cutoff and was resolved with treatment. Three deaths occurred by the time of interim analysis. One patient died of chronic hepatic failure, 1 patient died of pulmonary embolism, and the third patient died of multi-organ failure {hepatic failure as primary) that was attributed to cytomegalovirus-associated hemophagocytic lymphohistiocytosis.

MG-ADL scores across all symptom domains from REGAIN baseline to Week 130 in OLE3,4

Bulbar Symptoms

Talking; chewing; swallowing

The mean (SD) change in MG-ADL bulbar symptom domain score (95% Cl) from REGAIN baseline to Week 130 in the OLE study was 2.2 (1.26) points among patients receiving SOLIRIS/SOLIRIS vs 2.4 (1.56) points in patients receiving placebo/SOLIRIS (maximum score of 9).

Ocular Symptoms

Double vision; eye droop

The mean (SD) change in MG-ADL ocular symptom domain score (95% Cl) from REGAIN baseline to Week 130 in the OLE study was 1.4 (1.76) points among patients receiving SOLIRIS/SOLIRIS vs 1.9 (1.79) points in patients receiving placebo/SOLIRIS (maximum score of 6).

Limb/Gross Motor Symptoms

Impaired ability to rise from a chair; impaired ability to brush teeth or comb hair

The mean (SD) change in MG-ADL limb/gross motor symptom domain score (95% Cl) from REGAIN baseline to Week 130 in the OLE study was 1.6 (1.25) points among patients receiving SOLIRIS/SOLIRIS vs 2.1 (1.21) points in patients receiving placebo/SOLIRIS (maximum score of 6).

Respiratory Symptoms

Breathing

The mean (SD) change in MG-ADL respiratory symptom domain score (95% Cl) from REGAIN baseline to Week 130 in the OLE study was 0.7 (0.61) points among patients receiving SOLIRIS/SOLIRIS vs 0.7 (0.68) points in patients receiving placebo/SOLIRIS (maximum score of 3).
REGAIN OLE Study Limitation

Change from baseline in MG-ADL individual symptom domains was an exploratory endpoint. Any inference of efficacy or clinical significance should be interpreted with caution.

REGAIN OLE SELECT SAFETY OBSERVATIONS

Adverse events in the open-label extension study were consistent with REGAIN for up to 3 years. Infections were the most commonly reported adverse events of special interest. The most common serious AE was MG worsening (12.8%). There was 1 nonfatal case of meningococcal infection that was reported after data cutoff and was resolved with treatment. Three deaths occurred by the time of interim analysis. One patient died of chronic hepatic failure, 1 patient died of pulmonary embolism, and the third patient died of multi-organ failure (hepatic failure as primary) that was attributed to cytomegalovirus-associated hemophagocytic lymphohistiocytosis.

How SOLIRIS Works

Discover how SOLIRIS is thought to work in adult patients with anti-AChR antibody-positive gMG.

Explore MOA

Safety Profile of SOLIRIS

Learn about safety in REGAIN and the OLE study.


SEE THE DATA
Warning: Serious Meningococcal Infections
Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris and 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 Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. (See Serious Meningococcal Infections 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.
Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

Contraindications

  • Patients with unresolved serious Neisseria meningitidis infection
  • Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection

Warnings and Precautions

Serious Meningococcal Infections

Risk and Prevention

The use of Soliris increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis).

Vaccinate or revaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of Soliris. If Soliris must be initiated immediately in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide 2 weeks of antibacterial drug prophylaxis. Discontinue Soliris in patients who are undergoing treatment for serious meningococcal infections.

REMS

Prescribers must counsel patients about the risk of meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccine(s).

Other Infections

Serious infections with Neisseria species (other than N. meningitidis), including disseminated gonococcal infections, have been reported.

Patients may have increased susceptibility to infections, especially with encapsulated bacteria. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Use caution when administering Soliris to patients with any systemic infection.

Infusion-Related Reactions

Administration of Soliris may result in infusion-related reactions, including anaphylaxis or other hypersensitivity reactions. Interrupt Soliris infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

Adverse Reactions

The most frequently reported adverse reaction in the gMG placebo-controlled clinical trial (≥10%) is: musculoskeletal pain.

Indication

Generalized Myasthenia Gravis (gMG)

Soliris is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Please see full Prescribing Information for SOLIRIS, including Boxed WARNING regarding serious meningococcal infections.

Warning: Serious Meningococcal Infections
Life-threatening and fatal meningococcal infections have occurred in patients treated with Soliris and 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 Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. (See Serious Meningococcal Infections 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.
Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris REMS, prescribers must enroll in the program. Enrollment in the Soliris REMS program and additional information are available by telephone: 1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

Contraindications

  • Patients with unresolved serious Neisseria meningitidis infection
  • Patients who are not currently vaccinated against Neisseria meningitidis, unless the risks of delaying Soliris treatment outweigh the risks of developing a meningococcal infection

Warnings and Precautions

Serious Meningococcal Infections

Risk and Prevention

The use of Soliris increases a patient’s susceptibility to serious meningococcal infections (septicemia and/or meningitis).

Vaccinate or revaccinate for meningococcal disease according to the most current ACIP recommendations for patients with complement deficiencies. Immunize patients without a history of meningococcal vaccination at least 2 weeks prior to receiving the first dose of Soliris. If Soliris must be initiated immediately in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide 2 weeks of antibacterial drug prophylaxis. Discontinue Soliris in patients who are undergoing treatment for serious meningococcal infections.

REMS

Prescribers must counsel patients about the risk of meningococcal infection, provide the patients with the REMS educational materials, and ensure patients are vaccinated with meningococcal vaccine(s).

Other Infections

Serious infections with Neisseria species (other than N. meningitidis), including disseminated gonococcal infections, have been reported.

Patients may have increased susceptibility to infections, especially with encapsulated bacteria. Additionally, Aspergillus infections have occurred in immunocompromised and neutropenic patients. Use caution when administering Soliris to patients with any systemic infection.

Infusion-Related Reactions

Administration of Soliris may result in infusion-related reactions, including anaphylaxis or other hypersensitivity reactions. Interrupt Soliris infusion and institute appropriate supportive measures if signs of cardiovascular instability or respiratory compromise occur.

Adverse Reactions

The most frequently reported adverse reaction in the gMG placebo-controlled clinical trial (≥10%) is: musculoskeletal pain.

Indication

Generalized Myasthenia Gravis (gMG)

Soliris is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive.

Please see full Prescribing Information for SOLIRIS, including Boxed WARNING regarding serious meningococcal infections.

References:

  1. Howard JF Jr, et al. Lancet Neurol. 2017;16(12):976-986. doi:10.1016/S1474-4422(17)30369-1
  2. Muppidi S, et al. Muscle Nerve. 2019;60(1):14-24. doi:10.1002/mus.26447
  3. Mantegazza R, et al. Ann Clin Transl Neurol. 2020;7(8):1327-1339. doi:10.1002/acn3.51121
  4. Data on file. Alexion Pharmaceuticals, Inc. 2016.