Branaplam Receives Orphan Drug Designation for Huntington’s; Trial Planned for 2021

The U.S. Food and Drug Administration (FDA) has given orphan drug designation to the oral therapy branaplam (LMI070) as a potential treatment for Huntington’s disease, the therapy’s developer, Novartis, announced.

The designation is given to medications that have the potential to treat rare diseases — defined in the U.S. as disorders affecting less than 200,000 people — for which there is a high unmet need. It also qualifies Novartis for certain benefits and development incentives, including additional FDA support, tax credits, administrative waivers, and a seven-year period of marketing exclusivity following approval.

According to a press release, Novartis is planning to launch a Phase 2b clinical trial to assess the safety and effectiveness of branaplam in people with Huntington’s in 2021.

Branaplam was developed originally as a treatment for spinal muscular atrophy (SMA), a genetic, neurodegenerative disease in which the loss of motor neurons — nerve cells that control voluntary movements — results in progressive muscle weakness and motor function decline.

In SMA, branaplam works by increasing the levels of the survival motor neuron (SMN) protein, which is crucial for muscle health and is missing in people with the disease. The therapy does so by boosting the ability of a gene called SMN2, which is identical to the main gene that produces the protein and is faulty in SMA patients, to produce SMN.

Branaplam was first discovered by Novartis after screening approximately 1.4 million compounds for their ability to increase SMN levels. A Phase 1/2 trial (NCT02268552) assessing the safety, effectiveness, and pharmacological properties of the therapy in infants with type 1 SMA is ongoing.

Over the course of branaplam’s clinical testing in SMA, it was observed the experimental therapy was able to  reduce the levels of huntingtin messenger RNA — the molecule that cells use as a template to produce the huntingtin protein, which is abnormal in people with Huntington’s — in SMA patients.

In animal models, branaplam also has been shown to reduce the levels of mutant huntingtin protein.

These findings suggest the therapy may decrease the amount of mutant huntingtin protein in people with Huntington’s, which would be expected to provide therapeutic benefits. Based on the data, Novartis now is planning to launch a new clinical development program for branaplam specifically focused on Huntington’s.

There currently are no approved therapies for Huntington’s that tackle its underlying cause, and are able to delay its onset and halt its progression.

In people with SMA, branaplam is taken by mouth once per week. This same dosing regimen also may be a possibility for Huntington’s, though clinical testing will be needed to confirm its safety and effectiveness in this patient population.