REGAIN and Open-label Extension Study Designs

REGAIN and the open-label extension studies evaluated the efficacy and safety of SOLIRIS1,2

REGAIN PRIMARY ENDPOINT1

The primary endpoint was the change in MG-ADL total score from baseline to Week 26 for SOLIRIS compared to placebo.

REGAIN KEY SECONDARY ENDPOINT1

One secondary endpoint was the change in QMG total score from baseline to Week 26 for SOLIRIS compared to placebo.

OLE ENDPOINTS2

  • The primary objective was to evaluate the long-term safety of SOLIRIS, and the secondary objective was to evaluate long-term efficacy
    • The primary efficacy endpoint was change from baseline in mean MG-ADL total score over time
    • One secondary efficacy endpoint was change from baseline in mean QMG total scores over time

REGAIN and OLE Study Designs1,2

 

Data presented are from an interim analysis with a data cutoff of December 31, 2017.

After 26 weeks, patients who completed REGAIN were eligible to enter the open-label extension study.

Republished with permission of Muscle & Nerve. Permission conveyed through Copyright Clearance Center, Inc.

REGAIN PRIMARY ENDPOINT1

The primary endpoint was the change in MG-ADL total score from baseline to Week 26 for SOLIRIS compared to placebo.

REGAIN KEY SECONDARY ENDPOINT1

One secondary endpoint was the change in QMG total score from baseline to Week 26 for SOLIRIS compared to placebo.

OLE ENDPOINTS2

  • The primary objective was to evaluate the long-term safety of SOLIRIS, and the secondary objective was to evaluate long-term efficacy
  • The primary efficacy endpoint was change from baseline in mean MG-ADL total score over time
  • One secondary efficacy endpoint was change from baseline in mean QMG total scores over time

MG-ADL, Myasthenia Gravis Activities of Daily Living scale; QMG, Quantitative Myasthenia Gravis; SOC, standard of care.

Patients enrolled in REGAIN had inadequate gMG symptom control or were intolerant to previous therapies3

Key Inclusion Criteria for REGAIN3

  • Adults aged 18 years or older
  • Positive serologic test for anti-AChR antibodies
  • At least 1-year failure of ≥2 immunosuppressants or ≥1 immunosuppressant and required chronic PLEX or IVIg‡§
  • A total score ≥6 on the MG-ADL at screening
  • On stable dose of immunosuppressants or other concomitant medications
  • MGFA clinical classification: Class II to IV

Key Exclusion Criteria for REGAIN3

  • MGFA clinical classification Class I (ocular symptoms only) or Class V (MG crisis) at screening
  • History of thymectomy within 12 months prior to screening
  • History of thymoma or other neoplasms of the thymus
  • Use of IVIg or PLEX within 4 weeks prior to randomization (Day 1)
  • Use of rituximab within 6 months prior to screening

IVIg, intravenous immunoglobulin; MG, myasthenia gravis; MGFA, Myasthenia Gravis Foundation of America; PLEX, plasma exchange.

Immunosuppressant failure was defined as continued impairment of activities of daily living (persistent weakness, experienced crisis, or inability to tolerate immunosuppressants).4

Chronic PLEX or IVIg is defined as ≥4 treatments in a year (at least every 3 months over the previous 12 months).4

Patients were not required to be on immunosuppressants.4

SOLIRIS was studied across a range of disease severity3

Over 90% of patients were categorized as MGFA Class II or Class III

History of Trial Participants

  • 98% of patients received >2 ISTs at REGAIN baseline3
  • 46% received only 2 ISTs—including corticosteroids—at REGAIN baseline4
  • 28% received chronic IVIg, and 11% had received chronic PLEX3
  • Mean (SD) disease duration was 9.6 (8.2) years3
  • 78% had a history of MG exacerbations3
  • 18% had a history of MG crisis3

Patient Characteristics3

IST, immunosuppressant therapy; SD, standard deviation.

Exploratory Efficacy Analyses

View exploratory efficacy analyses from REGAIN and the OLE study.

GO TO EXPLORATORY ANALYSES

SOLIRIS Clinical Data

Learn more about REGAIN and the OLE studies and their endpoints.

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