FDA puts experimental gMG therapy cladribine on fast track
Approved MS treatment being repurposed, now in clinical testing
Cladribine could become the first oral treatment for generalized myasthenia gravis (gMG) in the U.S.
gMG is an autoimmune disorder causing widespread muscle weakness; cladribine aims to ease its symptoms.
The drug is being tested in a clinical trial dubbed MyClad that's now recruiting at 35 sites worldwide.
The U.S. Food and Drug Administration (FDA) has granted fast track designation to cladribine, an experimental oral treatment for generalized myasthenia gravis (gMG) that’s now in Phase 3 clinical testing.
Fast track status aims to expedite the clinical development and regulatory review of treatments with the potential to address an unmet medical need for serious conditions. With this designation, cladribine’s developer, Merck Kgaa (EMD Serono in North America), will have access to perks like more frequent communication with the FDA during the drug development process.
The new designation follows the FDA’s 2023 decision to name cladribine an orphan drug for gMG. Orphan drug designation is given to therapies designed to treat conditions that affect fewer than 200,000 people in the U.S., with the aim of incentivizing companies to develop new treatments for rare diseases.
According to Merck, cladribine, given as capsules, “[has] the potential to be the first oral treatment for people living with [this] rare, chronic autoimmune neuromuscular disorder.”
“The FDA’s fast track designation, together with orphan drug designation, affirms that more treatments are needed for the gMG community,” David Weinreich, MD, global head of R&D and chief medical officer for the healthcare business of Merck Kgaa, said in a company press release.
Myasthenia gravis (MG) is an autoimmune disease caused by self-reactive antibodies that interfere with the communication between nerve and muscle cells, leading to symptoms like muscle weakness. gMG is a form of the disease that affects several muscle groups, often causing widespread muscle weakness in the body.
Cladribine expected to ease symptoms as a gMG treatment
The autoimmune attack in MG is driven by B-cells and T-cells, two types of immune cells. Cladribine is a short-course therapy designed to kill these cells, which is expected to lower levels of self-reactive antibodies and ease symptoms.
The therapy is approved, under the brand name Mavenclad, for multiple sclerosis, another autoimmune disease. If cladribine were to be approved for gMG, it would be the first oral option for the disease, according to Merck.
Merck is running a global Phase 3 clinical trial called MyClad (NCT06463587) to test cladribine against a placebo in an estimated 264 adults with gMG. The trial, launched in 2024, is still recruiting participants at 35 sites worldwide.
In its first part, participants are randomly assigned to receive two short courses of either a low or high dose of cladribine, or a placebo, given about a month apart.
MyClad’s main goal is to determine whether cladribine is better than the placebo at reducing scores on the Myasthenia Gravis-Activities of Daily Living (MG-ADL) after six months. The MG-ADL is a standardized assessment of the extent to which MG causes issues in day-to-day life.
After about six months, the study will enter its second part, where participants originally assigned to cladribine will receive two short courses of the placebo, and vice versa. The study will also involve a retreatment period, in which patients may receive additional cladribine doses if clinically justified. The study has a total planned duration of more than 2.5 years.
Merck also working with medical equipment manufacturer on new tech in gMG
Merck noted that the trial was designed in collaboration with more than 20 MG advocacy organizations as well as a council of MG patients assembled expressly to ensure that the study will meet patients’ needs.
The company also recently announced a new collaboration with medical equipment manufacturing company Ad Scientiam to conduct a pilot study that will explore how wearable technology, smartphone-based tests, and electronic patient-reported outcomes might be deployed to aid in monitoring the course of gMG.
“As a patient-directed company, we are prioritizing the voices of MG patients in shaping our clinical program,” Weinreich said. “Their insights will continue to be instrumental to ensure we meet the needs of patients to deliver therapeutic innovation for this rare, chronic autoimmune neuromuscular disorder.”
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