Mayzent vs Mavenclad: Compare Efficacy, Safety & Considerations for MS

Introduction to Mayzent and Mavenclad

Mayzent (siponimod) and Mavenclad (cladribine) are both disease-modifying therapies used to treat relapsing forms of multiple sclerosis (MS). They work by targeting the immune system and reducing inflammation in the central nervous system that causes damage and disability in people with MS.

Mayzent is an S1P receptor modulator that prevents lymphocytes from leaving lymph nodes, reducing the number of lymphocytes available to cross the blood-brain barrier and cause inflammation. Mavenclad is considered an immunosuppressant that reduces lymphocyte counts.

While both drugs have proven effective for reducing relapses and disease progression, there are some key differences between Mayzent vs. Mavenclad that are important to understand when considering treatment options for MS.

Mechanism of Action

As mentioned above, Mayzent and Mavenclad have different mechanisms of action for impacting the immune system:

• Mayzent binds to S1P receptors on lymphocytes, preventing them from leaving lymph nodes and reducing circulating lymphocyte counts.
• Mavenclad kills off lymphocytes by incorporating into their DNA as they divide, leading to lower lymphocyte counts.

Both mechanisms serve to reduce autoimmune attacks on the central nervous system, but act in different ways. Some doctors and patients may have a preference for a functional approach like Mayzent versus a cytotoxic approach like Mavenclad.

Administration and Dosing

The dose and administration schedules also differ between Mayzent and Mavenclad:

• Mayzent is a daily oral tablet taken consistently.
• Mavenclad is taken as two treatment courses one year apart, with each course consisting of two treatment cycles a month apart.

This makes Mavenclad a less frequent dosing option, which can be preferable for some patients. However, it requires more intensive monitoring between courses.

Monitoring Requirements

Due to their effects on the immune system, Mayzent and Mavenclad require safety monitoring:

• Mayzent requires occasional blood tests to monitor lymphocyte counts.
• Mavenclad requires blood tests before, during and after treatment to monitor for severe lymphopenia and signs of infection.

Doctors also monitor liver function with both therapies. Mavenclad carries a higher risk of serious infections compared to Mayzent due to the cyclical lymphocyte depletion.

Usage Considerations

Some additional factors to consider when weighing Mayzent vs. Mavenclad for MS treatment include:

• Mayzent stays in the body for up to one month after stopping treatment, while Mavenclad is only present during the treatment cycles.
• Mavenclad is not recommended for use in patients with HIV, hepatitis B/C, TB or other chronic infections.
• Both drugs have special considerations regarding contraception and pregnancy planning due to potential fetal risks.
• Mavenclad is only approved for active relapsing MS, while Mayzent is also approved for secondary progressive MS.

Efficacy

Understanding the efficacy of Mayzent versus Mavenclad can help inform treatment decisions. Key clinical trial findings include:

Mayzent

• In the EXPAND trial, Mayzent reduced annualized relapse rates by 48% compared to placebo over 21 months.
• It reduced disability progression confirmed at 3 months by 21% compared to placebo.
• MRI scans showed Mayzent substantially reduced inflammatory lesion activity.

Mavenclad

• The CLARITY study found Mavenclad reduced annualized relapse rates by 58% over 2 years compared to placebo.
• It reduced disability progression sustained for 6 months by 72% compared to placebo.
• MRI scans showed 90% fewer new inflammatory lesions with Mavenclad at 2 years.

While both therapies demonstrated robust efficacy for measures like reducing relapse rates, Mayzent showed relatively greater effects on disability outcomes compared to placebo than Mavenclad.

Comparative Data

There are no head-to-head trials directly comparing Mayzent vs. Mavenclad for MS treatment. However, indirect analyses and real-world data provide some insights:

• An indirect comparison of clinical trials found annualized relapse rate reductions were comparable between Mayzent and Mavenclad.
• Real-world data on relapse rates and discontinuation rates suggested relatively similar effectiveness.
• Some analyses indicate Mayzent may limit disability progression to a greater degree based on clinical trial data.

Overall, both therapies demonstrate robust efficacy for managing relapsing-remitting MS, with Mayzent showing some additional benefits for non-relapsing secondary progressive disease.

Safety

The safety profiles of Mayzent and Mavenclad are also an important consideration when weighing the treatment options:

Common Side Effects

Mayzent and Mavenclad have some overlapping common side effects, but also some differences:

• Mayzent - Headache, hypertension, transaminase increases
• Mavenclad - Headache, upper respiratory tract infections, nausea

Mavenclad has been associated with a higher risk of infections compared to Mayzent due to the cyclical immunosuppression.

Serious Risks

Both therapies require monitoring due to potential serious risks:

• Mayzent - Bradyarrhythmia, macular edema, liver injury, shingles
• Mavenclad - Severe lymphopenia, malignancies, fetal harm

Mavenclad carries black box warnings for fetal toxicity and malignancy risk. Progressive multifocal leukoencephalopathy has also been reported rarely with Mavenclad treatment.

Discontinuation Rates

Discontinuation rates due to adverse effects provide additional insights into safety and tolerability:

• Clinical trials showed ~7-10% of Mayzent patients stopped treatment due to side effects.
• ~4% of Mavenclad patients discontinued due to adverse effects in trials.

This suggests Mavenclad may be slightly better tolerated overall, but Mayzent still demonstrates a manageable safety profile for most patients.

Access and Cost

Finally, access and cost considerations also play a role in the Mayzent vs. Mavenclad decision:

• Mayzent has a list price of over $85,000 per year.
• A course of Mavenclad is priced at ~$125,000-175,000.

Both therapies are covered by most major insurers, but tend to require prior authorization and have tiered formulary placement given the high costs. Financial assistance programs are available for each medication.

Mavenclad's less frequent dosing schedule reduces annual medication costs once coverage is obtained. But both therapies ultimately represent a significant cost burden for payers and patients.

Key Differences and Considerations

In summary, here are some of the key differences between Mayzent and Mavenclad:

• Mayzent is an S1P receptor modulator, while Mavenclad is a cytotoxic immunosuppressant.
• Mavenclad is dosed less frequently but requires more intensive monitoring.
• Both drugs reduce relapse rates, but Mayzent showed comparatively greater effects on disability progression.
• Mavenclad carries higher risks related to infections and fetal toxicity.
• Mavenclad is more affordable long-term but requires high upfront costs.

Choosing between these two effective MS therapies involves balancing efficacy, safety, tolerability, and access considerations in light of individual patient circumstances.

Which Patients May Benefit More From Mayzent?

Some examples of patients who may derive greater benefit from Mayzent include:

• Those seeking an oral daily medication option
• People with secondary progressive MS
• Those concerned about infection risk with Mavenclad
• Patients who progressed on other MS therapies

Which Patients May Benefit More From Mavenclad?

Here are examples of patients who may derive more benefit from Mavenclad:

• Those looking for a less frequent dosing schedule
• People unable to get insurance coverage for a costlier therapy like Mayzent
• Patients concerned about Mayzent's effects on heart rate
• Those looking for rapid control of highly active relapsing MS

Careful consideration of individual disease and lifestyle factors can help determine whether Mayzent or Mavenclad is the more appropriate treatment option.

The Takeaway

Both Mayzent and Mavenclad offer effective new therapeutic choices for managing relapsing forms of multiple sclerosis. While they share similarities in efficacy for reducing MS relapses, they have key differences in mechanisms of action, dosing schedules, safety/tolerability, and costs.

Choosing between Mayzent vs. Mavenclad involves assessing an individual's disease status, lifestyle needs, and tolerance for potential side effects. This allows customization of treatment based on the benefits and risks most relevant to each patient's circumstances and values. Shared decision-making between people with MS and their healthcare providers ultimately optimizes the personalized use of these transformative therapies.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult with a healthcare professional before starting any new treatment regimen.