REGAIN and Open-label Extension Clinical Data

Rapid and sustained* improvement in MG-ADL scores in REGAIN1

  • Primary Endpoint in REGAIN: 4.2-point improvement in mean MG-ADL total score from baseline to Week 26 among patients receiving SOLIRIS vs 2.3-point improvement in patients receiving placebo (P=0.006)1
  • Patients receiving SOLIRIS showed improvement in MG-ADL as early as 4 weeks after treatment initiation, which was sustained* for the duration of the 26-week study. Available data suggest that clinical response is usually achieved by 12 weeks of SOLIRIS treatment3
    • Separation in MG-ADL total scores was observed as early as Week 1 but not considered clinically meaningful (≥3-point improvement) prior to Week 43
REGAIN Study Limitation

Time to response was an exploratory endpoint; therefore, results should be interpreted with caution.

CI, confidence interval; MG-ADL, Myasthenia Gravis Activities of Daily Living scale; SD, standard deviation.

MG-ADL in Phase 3 REGAIN Study1,2

 
  • Primary Endpoint in REGAIN: 4.2-point improvement in mean MG-ADL total score from baseline to Week 26 among patients receiving SOLIRIS vs 2.3-point improvement in patients receiving placebo (P=0.006)1
  • Patients receiving SOLIRIS showed improvement in MG-ADL as early as 4 weeks after treatment initiation, which was sustained* for the duration of the 26-week study. Available data suggest that clinical response is usually achieved by 12 weeks of SOLIRIS treatment3
    • Separation in MG-ADL total scores was observed as early as Week 1 but not considered clinically meaningful (≥3-point improvement) prior to Week 43
REGAIN Study Limitation

Time to response was an exploratory endpoint; therefore, results should be interpreted with caution.

CI, confidence interval; MG-ADL, Myasthenia Gravis Activities of Daily Living scale; SD, standard deviation.

SELECT IMPORTANT SAFETY INFORMATION
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

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

Improvement in muscle weakness (QMG) in REGAIN1,3

QMG in Phase 3 REGAIN Study1,3

 

Improvement in muscle weakness (QMG) in REGAIN1,3

  • Key Secondary Endpoint in REGAIN: 4.6-point improvement in mean QMG total score from baseline to Week 26 among patients receiving SOLIRIS vs 1.6-point improvement in patients receiving placebo; improvement was nearly 3 times that of placebo
    • Separation in QMG total scores was observed as early as Week 2 but not considered clinically meaningful (defined as ≥5-point improvement)

QMG, Quantitative Myasthenia Gravis.

SELECT IMPORTANT SAFETY INFORMATION
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.

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

Significant improvement in activities of daily living (MG-ADL)3

60% of patients receiving SOLIRIS during REGAIN had ≥3-point improvement in MG-ADL total score at Week 26*

Based on a prespecified analysis of patients with ≥3-point reduction in MG-ADL total score (clinical responder) and who received no rescue therapy during REGAIN at 26 weeks.4

 
≥8-POINT IMPROVEMENT

21%

of SOLIRIS-treated patients experienced an improvement of ≥8 points in MG-ADL total scores compared to 6% with placebo (P=0.0176)

≥7-POINT IMPROVEMENT

34%

of SOLIRIS-treated patients experienced an improvement of ≥7 points in MG-ADL total scores compared to 10% with placebo (P=0.0007)

≥5-POINT IMPROVEMENT

45%

of SOLIRIS-treated patients experienced an improvement of ≥5 points in MG-ADL total scores compared to 25% with placebo (P=0.0182)

≥3-POINT IMPROVEMENT

60%

of SOLIRIS-treated patients experienced an improvement of ≥3 points in MG-ADL total scores compared to 40% with placebo (P=0.0229)

SELECT IMPORTANT SAFETY INFORMATION
Warnings and Precautions
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).

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

Review the MG-ADL scale, a tool that assesses which symptoms most affect patients’ daily living.

View the mg-adl profile

Rapid and sustained improvement in activities of daily living (MG-ADL)* through 26 weeks in REGAIN and observed through Week 130 of the OLE study2,4

REGAIN OLE Study Limitation

Any inference of efficacy or clinical significance should be interpreted with caution since the study was designed to evaluate safety and lacked a control group.

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.

*Patients receiving SOLIRIS showed improvement in MG-ADL in as early as 4 weeks after treatment initiation. This improvement was found to be sustained for the duration of the 26-week study. Available data suggest that clinical response is usually achieved by 12 weeks of SOLIRIS treatment.

MG-ADL in Phase 3 REGAIN and OLE Studies2,4

 
REGAIN OLE Study Limitation

Any inference of efficacy or clinical significance should be interpreted with caution since the study was designed to evaluate safety and lacked a control group.

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.

*Patients receiving SOLIRIS showed improvement in MG-ADL in as early as 4 weeks after treatment initiation. This improvement was found to be sustained for the duration of the 26-week study. Available data suggest that clinical response is usually achieved by 12 weeks of SOLIRIS treatment.

Improvements in muscle weakness (QMG) demonstrated in REGAIN were observed through Week 130 of the OLE study4

QMG in Phase 3 REGAIN and OLE Studies4

 

Improvements in muscle weakness (QMG) demonstrated in REGAIN were observed through Week 130 of the OLE study4

REGAIN OLE Study Limitation

Any inference of efficacy or clinical significance should be interpreted with caution since the study was designed to evaluate safety and lacked a control group.

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.

Safety Profile of SOLIRIS

Learn about safety in REGAIN and the OLE study.

SEE THE DATA

Exploratory Efficacy Analyses

View exploratory efficacy analyses from REGAIN and the OLE study.

Go to exploratory analyses
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. SOLIRIS. Prescribing information. Alexion Pharmaceuticals, Inc.
  2. Data on file. Alexion Pharmaceuticals, Inc. 2016.
  3. Howard JF Jr, et al. Lancet Neurol. 2017;16(12):976-986. doi:10.1016/S1474-4422(17)30369-1
  4. Muppidi S, et al. Muscle Nerve. 2019;60(1):14-24. doi:10.1002/mus.26447