ROCKLAND, Mass--(
BUSINESS WIRE
)--EMD Serono, the Healthcare business of Merck KGaA, Darmstadt, Germany, in the U.S. and Canada, today announced the presentation of two new post-hoc analyses of tertiary endpoints from the MAGNIFY-MS study, a Phase IV, prospective, open-label study evaluating the efficacy and safety of MAVENCLAD
®
(cladribine) tablets in highly active relapsing multiple sclerosis (RMS). The first presentation examines the stability or improvement in cognitive processing speed over a two-year period, suggesting the potential of MAVENCLAD to maintain or improve cognitive function in patients with highly active RMS. Additionally, interim findings from year three of the MAGNIFY-MS extension trial underscore the continued efficacy and safety profile of MAVENCLAD, which is consistent with earlier safety data. These data are being presented at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2024.
The post-hoc analysis from 270 patients showed a clinically meaningful benefit in cognitive processing speed in patients treated with MAVENCLAD. Cognitive benefit was seen following the first treatment course and became more pronounced by month 18 when patients had received the full treatment course. At two years, the estimated rate of stability or sustained improvement was more than 95% with an 8-point score change on the Symbol Digit Modality Test (SDMT), a measure of cognitive processing speed.
“Our decades of experience in multiple sclerosis have brought us clarity around the cognitive issues that affect over half of individuals with MS,” said Lori Lebson, Senior Vice President, North America Medical Affairs, EMD Serono. “Based on these findings from MAGNIFY-MS, where the majority of patients on MAVENCLAD had either cognitive improvement or stability at two years, we are optimistic about a future where the burden of cognitive changes in MS can be reduced.”
Cognitive symptoms often have a profound impact on daily living and the quality of life in people living with MS. They can touch multiple aspects of a person’s life, such as employment, social life, including relationships, and even participating in their own healthcare decisions.
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Also being presented are the year three findings from an interim analysis of the extension trial of the MAGNIFY-MS study which showed sustained efficacy of MAVENCLAD, one year following completion of the two treatment courses. The No Evidence of Disease Activity-3 (NEDA-3) rates during year three were 85.99% for treatment naïve and 76.86% for those previously treated, based on the assessment of 219 patients. NEDA-3 status is defined as patients with no relapse, no 6-month Expanded Disability Status Scale (EDSS) progression and no T1 gadolinium-enhancing (Gd+) or active T2 lesions. The majority of patients (90.4%) were free of qualifying relapses and overall EDSS remained stable. Sustained improvements in MRI outcomes were seen: T1 Gd+ counts and annualized active T2 lesion counts showed a decrease from baseline to month 24 and month 36. These findings further support the continued benefits of MAVENCLAD following completion of the two-year treatment course.
About MAVENCLAD
®
MAVENCLAD, approved by the U.S. Food and Drug Administration (FDA) on March 29, 2019, is the first and only short-course oral therapy for the treatment of adults with relapsing-remitting disease (RRMS) and active secondary progressive disease (SPMS). Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of multiple sclerosis (MS), and MAVENCLAD is not recommended for use in patients with clinically isolated syndrome (CIS). Patients should follow healthcare provider instructions including cancer screening, contraception and blood tests. The approved dose of MAVENCLAD is 3.5 mg per kg body weight over two years, administered as one treatment course of 1.75 mg per kg per year, each consisting of two treatment weeks. The mechanism by which cladribine exerts its therapeutic effects in patients with multiple sclerosis has not been fully elucidated but is thought to involve cytotoxic effects on B and T lymphocytes through impairment of DNA synthesis, resulting in depletion of lymphocytes. MAVENCLAD causes a dose-dependent reduction in lymphocyte counts followed by recovery.
Because cladribine is cytotoxic, special handling and disposal instructions should be followed.
IMPORTANT SAFETY INFORMATION
WARNING: MALIGNANCIES and RISK OF TERATOGENICITY
Treatment with MAVENCLAD may increase the risk of malignancy. MAVENCLAD is contraindicated in patients with current malignancy. In patients with prior malignancy or with increased risk of malignancy, evaluate the benefits and risks of the use of MAVENCLAD on an individual patient basis. Follow standard cancer screening guidelines in patients treated with MAVENCLAD.
MAVENCLAD is contraindicated for use in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception because of the potential for fetal harm. Malformations and embryolethality occurred in animals. Exclude pregnancy before the start of treatment with MAVENCLAD in females of reproductive potential. Advise females and males of reproductive potential to use effective contraception during MAVENCLAD dosing and for 6 months after the last dose in each treatment course. Stop MAVENCLAD if the patient becomes pregnant.
CONTRAINDICATIONS
Patients with current malignancy.
Pregnant women, and women and men of reproductive potential who do not plan to use effective contraception during and for 6 months after the last dose in each treatment course. May cause fetal harm.
Patients infected with human immunodeficiency virus (HIV).
Patients with active chronic infections (e.g., hepatitis or tuberculosis).
Patients with a history of hypersensitivity to cladribine.
Women intending to breastfeed on a MAVENCLAD treatment day and for 10 days after the last dose.
WARNINGS AND PRECAUTIONS
Malignancies:
Treatment with MAVENCLAD may increase the risk of malignancy. After the completion of 2 treatment courses, do not administer additional MAVENCLAD treatment during the next 2 years. In clinical studies, patients who received additional MAVENCLAD treatment within 2 years after the first 2 treatment courses had an increased incidence of malignancy. The risk of malignancy with reinitiating MAVENCLAD more than 2 years after the completion of 2 treatment courses has not been studied. Follow standard cancer screening guidelines in patients treated with MAVENCLAD.
Risk of Teratogenicity:
MAVENCLAD may cause fetal harm when administered to pregnant women. In females of reproductive potential, exclude pregnancy before initiation of each treatment course of MAVENCLAD and prevent by the use of effective contraception during MAVENCLAD dosing and for at least 6 months after the last dose of each treatment course. Women who become pregnant during treatment with MAVENCLAD should discontinue treatment.
Lymphopenia:
MAVENCLAD causes a dose-dependent reduction in lymphocyte count. Concomitant use of MAVENCLAD with hematotoxic drugs may increase the risk of adverse reactions because of the additive hematological effects. Monitor lymphocyte counts before, during, and after treatment.
Infections:
Serious, including life-threatening or fatal, infections have occurred. MAVENCLAD reduces the body's immune defense, and an increased risk of infections has been observed in patients receiving MAVENCLAD. Infections occurred in 49% of MAVENCLAD-treated patients compared to 44% of patients treated with placebo in clinical studies; serious or severe infections occurred in 2.4% of MAVENCLAD- treated patients and 2.0% of placebo-treated patients. The most frequent serious infections included herpes zoster and pyelonephritis. Fungal infections were observed, including cases of coccidioidomycosis. Single fatal cases of tuberculosis and fulminant hepatitis B were reported in the clinical program.
Screen patients for active and latent infections (tuberculosis, hepatitis B or C). Delay treatment until infection is fully resolved or controlled.
Vaccinate patients who are seronegative for varicella zoster virus (VZV) prior to treatment. Vaccinate patients who are seropositive to VZV with recombinant, adjuvanted zoster vaccine either prior to or during treatment, including when their lymphocyte counts are less than or equal to 500 cells per microliter.
Administer anti-herpes prophylaxis in patients with lymphocyte counts less than 200 cells per microliter. Monitor for infections.
Progressive multifocal leukoencephalopathy (PML) has been reported in patients treated with parenteral cladribine for oncologic indications. No case of PML has been reported in clinical studies of cladribine in patients with MS. Obtain a baseline magnetic resonance imaging (MRI) within 3 months before initiating the first treatment course of MAVENCLAD. At the first sign of PML, withhold MAVENCLAD and perform an evaluation.
Administer all immunizations (except as noted for VZV) according to immunization guidelines prior to starting MAVENCLAD. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting MAVENCLAD due to risk of infection.
Hematologic Toxicity:
In addition to lymphopenia, decreases in other blood cells and hematological parameters have been reported with MAVENCLAD in clinical studies. Obtain complete blood count (CBC) with differential including lymphocyte count before and during treatment, periodically thereafter, and when clinically indicated.
Graft-versus-Host Disease with Blood Transfusions:
Transfusion-associated graft-versus-host disease has been observed rarely after transfusion of nonirradiated blood in patients treated with cladribine for non-MS treatment indications. In patients who require blood transfusion, irradiation of cellular blood components is recommended.
Liver Injury:
In clinical studies, 0.3% of MAVENCLAD-treated patients had liver injury (serious or causing treatment discontinuation) compared to 0 placebo patients. Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels prior to treatment. Discontinue MAVENCLAD if clinically significant liver injury is suspected.
Hypersensitivity:
If a hypersensitivity reaction is suspected, discontinue MAVENCLAD therapy. Do not use MAVENCLAD in patients with a history of hypersensitivity to cladribine.
Cardiac Failure:
In clinical studies, one MAVENCLAD-treated patient experienced life-threatening acute cardiac failure with myocarditis, which improved after approximately one week. Cases of cardiac failure have also been reported with parenteral cladribine used for treatment indications other than multiple sclerosis. Instruct patients to seek medical advice if they experience symptoms of cardiac failure (e.g., shortness of breath, rapid or irregular heartbeat, swelling).
Adverse Reactions:
The most common adverse reactions (incidence of >20%) are upper respiratory tract infection, headache, and lymphopenia.
Drug Interactions:
Concomitant use of with immunosuppressive or myelosuppressive drugs and some immunomodulatory drugs (e.g., interferon beta) is not recommended and may increase the risk of adverse reactions. Acute short-term therapy with corticosteroids can be administered. Monitor for additive effects on the hematological provide with use of hemotoxic drugs. Avoid concomitant use of antiviral and antiretroviral drugs. Avoid concomitant use of BCRP or ENT/CNT inhibitors as they may alter bioavailability of MAVENCLAD.
Use in Specific Populations:
Studies have not been performed in pediatric, or elderly patients >65 years, pregnant or breastfeeding women. Use in patients with moderate to severe renal or hepatic impairment is not recommended.
To report SUSPECTED ADVERSE REACTIONS, contact EMD Serono, Inc. at 1-800-283-8088 ext. 5563 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch
.
Please see the full
Prescribing Information
, including
BOXED WARNING
for additional information.
About Multiple Sclerosis
Multiple sclerosis (MS) is a chronic, inflammatory condition of the central nervous system and is the most common non-traumatic, disabling neurological disease in young adults. It is estimated that approximately 2.8 million people have MS worldwide. While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of MS are the most common.
EMD Serono, Inc. and Multiple Sclerosis
For more than 20 years, EMD Serono has been relentlessly focused on understanding the journey people living with MS face in order to create a meaningful, positive experience for them and the broader MS community. However, there is still much that is unknown about this complex and unpredictable disease. EMD Serono is digging deeper to advance the science.
About EMD Serono, Inc.
EMD Serono - the healthcare business of Merck KGaA, Darmstadt, Germany in the U.S. and Canada - aspires to create, improve and prolong life for people living with difficult-to-treat conditions like infertility, multiple sclerosis and cancer. The business is imagining the future of healthcare by working to translate the discovery of molecules into potentially meaningful outcomes for people with serious unmet medical needs. EMD Serono’s global roots go back more than 350 years with Merck KGaA, Darmstadt, Germany. Today, the business has approximately 1,500 employees around the country with commercial, clinical and research operations in Massachusetts.
www.emdserono.com
.
About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, a leading science and technology company, operates across life science, healthcare and electronics. More than 64,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2022, Merck KGaA, Darmstadt, Germany, generated sales of € 22.2 billion in 66 countries.
The company holds the global rights to the name and trademark “Merck” internationally. The only exceptions are the United States and Canada, where the business sectors of Merck KGaA, Darmstadt, Germany, operate as MilliporeSigma in life science, EMD Serono in healthcare and EMD Electronics in electronics. Since its founding in 1668, scientific exploration and responsible entrepreneurship have been key to the company’s technological and scientific advances. To this day, the founding family remains the majority owner of the publicly listed company.
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Morrow SA, Kruger P, Langdon D, Alexandri N. What Is the True Impact of Cognitive Impairment for People Living with Multiple Sclerosis? A Commentary of Symposium Discussions at the 2020 European Charcot Foundation.
Neurol Ther.
2023 Oct;12(5):1419-1429. doi: 10.1007/s40120-023-00519-z. Epub 2023 Jul 19. PMID: 37466762; PMCID: PMC10444737.
