Novartis Announces FDA Orphan Drug Designation for Branaplam (LMI070) in Huntington’s Disease

Compiled by Keke

On October 21, Novartis announced that the U.S. FDA had granted orphan drug designation to branaplam (LMI070), a drug for the treatment of Huntington’s disease (HD). Orphan drug designation is a special status awarded to drugs intended to treat rare diseases or conditions, providing pharmaceutical companies with certain incentives to encourage the continued development of therapies that offer new solutions for patients with serious diseases.

In preclinical studies, branaplam has been demonstrated to reduce levels of mutant huntingtin protein. Furthermore, in studies involving patients with spinal muscular atrophy (SMA) treated with branaplam, the drug was observed to decrease huntingtin messenger RNA (mRNA) levels. The reduction in huntingtin mRNA may lead to decreased levels of huntingtin protein, which is the fundamental goal of Huntington’s disease (HD) therapy. Based on these findings, Novartis plans to initiate a development program for branaplam to determine whether the drug has the potential to serve as a disease-modifying treatment for patients with SMA.

Huntington’s disease (HD) is a rare hereditary neurodegenerative disorder that leads to progressive disability and death. Everyone carries the huntingtin (HTT) gene, but only individuals with mutations in this gene develop the disease. HD is characterized by the gradual worsening of motor, cognitive, and psychiatric symptoms. These symptoms typically onset between the ages of 30 and 50 and progress over a period of 15–20 years. Approximately 70,000 individuals in Europe and the United States have been clinically diagnosed with HD. Currently, treatment options for HD are limited to symptomatic management, and there are no approved disease-modifying therapies that can delay the onset or slow the progression of the disease.

Branaplam (LMI070) is a small-molecule RNA splicing modulator belonging to the pyridazine derivative class. It increases the functional levels of survival motor neuron protein by altering the splicing pattern of the survival motor neuron 2 (SMN2) gene and is currently under investigation for the treatment of spinal muscular atrophy (SMA). SMA is a rare, progressive genetic disorder characterized by the loss of motor neurons responsible for muscle function. Novartis has stated that branaplam is administered once weekly for the treatment of SMA, and the same dosing regimen may also be applicable for Huntington’s disease (HD). Consequently, the company plans to initiate a Phase IIb clinical trial of branaplam in patients with HD in 2021.

Branaplam molecular structure (Source: Wikipedia)

Reference Source:

1. Wikipedia

2.Novartis receives US Food and Drug Administration (FDA) Orphan Drug Designation for branaplam (LMI070) in Huntington’s disease (HD)