Developer creates under-the-tongue cladribine for testing in MS

A new formulation — a film that dissolves under the tongue — of cladribine for treating multiple sclerosis (MS) has moved closer to clinical testing, according to an update from its developer.

Bionxt Solutions announced that it has completed manufacturing of a clinical-grade batch of BNT23001, its sublingual, or under-the-tongue, formulation of cladribine. The batch was manufactured in accordance with European Union Good Manufacturing Practice (GMP) standards, a set of regulatory requirements that ensure medicines are consistently produced and controlled for quality, the developer said in a company press release.

Produced by the company’s manufacturing partner, Gen-Plus, the completed batch is intended for use in an upcoming human study. That study will compare whether BNT23001 delivers the same amount of cladribine to the bloodstream as Mavenclad, the approved oral tablet formulation of cladribine.

BNT23001 is formulated as a thin film that quickly dissolves under the tongue to deliver the drug directly into the bloodstream. It is designed to offer a different administration option for people with MS who have difficulty swallowing, a common MS symptom.

According to Bionxt, completing GMP manufacturing marks the final technical step before clinical trial activation and first-in-human dosing of BNT23001.

“Completing GMP manufacturing of our clinical-grade Cladribine ODF [oral dissolvable film] is a defining milestone for BioNxt,” said Hugh Rogers, the company’s CEO. “This achievement demonstrates our ability to translate innovative formulation science into regulator-ready clinical supply and brings us closer to generating human data.”

BNT23001’s manufacturing involved validated production processes, controlled sourcing of raw materials, and comprehensive in-process controls and quality testing, with stability studies now underway, the company said. Bionxt added that it will “provide further updates regarding clinical trial activation and first [participant] dosing in due course.”

Cladribine is the active ingredient in the approved MS drug Mavenclad

Mavenclad is a short-course oral treatment approved for relapsing forms of MS, including relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS). It works by lowering the number of certain immune cells, namely T-cells and B-cells, that drive inflammation and nerve damage in MS.

In clinical trials, Mavenclad has been shown to reduce MS disease activity and disability accumulation, with benefits lasting several years after treatment stops. Long-term follow-up showed that more than half of treated patients did not require additional disease-modifying therapies for nearly 11 years after their initial treatment.

By dissolving under the tongue, BNT23001 allows cladribine to be absorbed through the lining of the mouth, avoiding passage through the gastrointestinal tract.

According to Bionxt, this approach could help make drug absorption and blood exposure more consistent than with traditional oral medications, while also offering a more user-friendly option for people who have difficulty swallowing tablets.

The formulation, which is expected to act faster than the tablet form, may also help improve adherence to treatment, the company said.

Preclinical studies in animal models showed that BNT23001 was rapidly absorbed and provided a comparable cladribine exposure to Mavenclad. No signs of toxicity were observed after repeated dosing over consecutive days.

In a more recent study in adult miniature pigs, the sublingual formulation resulted in about 40% higher blood exposure to cladribine than the standard oral tablet formulation.

“We believe this milestone substantially advances our strategy to position BioNxt as a leader in next-generation, needle-free drug delivery systems,” Rogers said.