National Stroke Foundation

Mavenclad (cladribine)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved March 2019

Specific Treatments:

relapsing multiple sclerosis

Therapeutic Areas

General Information

Mavenclad (cladribine) is a purine antimetabolite. 

Mavenclad is specifically indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. 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 MS.

Mavenclad is supplied as a tablet for oral administration. Mavenclad can be taken with or without food. The tablets can be taken with water and swallowed whole without chewing. Prior to administration patients should be screened for the following:

• Cancer due to increased risk of malignancies (see side effects)

• Pregnancy

• Complete Blood Count (CBC): obtain a CBC with differential including lymphocyte count

• Infections including HIV, tuberculosis, hepatitis B and C and acute infections. Vaccination of patients who are antibody-negative for varicella zoster virus is recommended prior to initiation of Mavenclad. Administer all immunizations according to immunization guidelines prior to starting Mavenclad. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting Mavenclad. Obtain a baseline (within 3 months) magnetic resonance imaging prior to the first treatment course because of the risk of progressive multifocal leukoencephalopathy.

• Liver injury: Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels

The recommended cumulative dosage of Mavenclad is 3.5 mg per kg body weight administered orally and divided into 2 yearly treatment courses (1.75 mg per kg per treatment course) . Please refer to drug label for weight-based chart. Each treatment course is divided into 2 treatment cycles:

Administration of First Treatment Course

• First Course/First Cycle: start any time.

• First Course/Second Cycle: administer 23 to 27 days after the last dose of First Course/First Cycle.

Administration of Second Treatment Course

• Second Course/First Cycle: administer at least 43 weeks after the last dose of First Course/Second Cycle.

• Second Course/Second Cycle: administer 23 to 27 days after the last dose of Second Course/First Cycle.

Administer the cycle dosage as 1 or 2 tablets once daily over 4 or 5 consecutive days. Do not administer more than 2 tablets daily. Following the administration of 2 treatment courses, do not administer additional Mavenclad treatment during the next 2 years. Treatment during these 2 years may further increase the risk of malignancy.

If a dose is missed, patients should not take double or extra doses. If a dose is not taken on the scheduled day, then the patient must take the missed dose on the following day and extend the number of days in that treatment cycle. If two consecutive doses are missed, the treatment cycle is extended by 2 days.


 

Clinical Results

FDA Approval

The FDA approval of Mavenclad was based on a 96-week randomized, double-blind, placebo-controlled clinical study in patients with relapsing forms of MS. Patients were required to have at least 1 relapse in the previous 12 months. The median age was 39 years and over two thirds of the study patients were treatment-naive for drugs used to treat relapsing forms of MS. The trial enrolled 1,326 patients who were randomized to receive either placebo (n = 437), or a cumulative oral dosage of Mavenclad 3.5 mg per kg (n = 433) or 5.25 mg per kg body weight (n = 456) over the 96-week study period in 2 treatment courses. Patients randomized to the 3.5 mg per kg cumulative dose received a first treatment course at Weeks 1 and 5 of the first year and a second treatment course at Weeks 1 and 5 of the second year. Patients randomized to the 5.25 mg per kg cumulative dose received additional treatment at Weeks 9 and 13 of the first year. Higher cumulative doses did not add any clinically meaningful benefit, but were associated with a higher incidence in grade 3 lymphopenia or higher (44.9% in the 5.25 mg per kg group vs. 25.6% in the 3.5 mg per kg group). Ninety-two percent of patients treated with Mavenclad 3.5 mg per kg and 87% of patients receiving placebo completed the full 96 weeks of the study. The primary outcome of Study 1 was the annualized relapse rate (ARR). Mavenclad 3.5 mg per kg cumulative dose significantly lowered the ARR; patients experienced a 58% relative reduction compared to placebo (0.14 vs. 0.33, p<0.001). In addition, 81% of patients were free of relapses after two years of short-course oral treatment with Mavenclad, compared to 63% of patients who received placebo (p<0.05). Patients treated with Mavenclad had a 33% reduction in risk of 3-month confirmed disability progression as measured by Expanded Disability Status Scale (EDSS) compared to placebo (p<0.05). Patients taking Mavenclad experienced a lower median number of T1-weighted gadolinium-enhanced brain lesions and new or enlarging T2 brain lesions compared to patients with placebo (0 vs. 0.33 and 0 vs. 0.67, p<0.001).

Side Effects

Adverse effects associated with the use of Mavenclad may include, but are not limited to, the following:

upper respiratory tract infection

headache

lymphopenia

The Mavenclad drug label comes with the following Black Box Warning: Mavenclad may increase the risk of malignancy. Mavenclad is contraindicated in patients with current malignancy; evaluate the benefits and risks on an individual basis for patients with prior or increased risk of malignancy. Risk of Teratogenicity: 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 risk of fetal harm.

Mechanism of Action

Mavenclad (cladribine) is a purine antimetabolite. 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.

Additional Information

For additional information regarding Mavenclad or relapsing-remitting disease and active secondary progressive disease, please visit https://www.mavenclad.com/en/now-approved/index