FDA approves orphan drug status for Lupin’s mexiletine

Lupin, one of the top five Indian pharmaceutical companies in terms of revenue, announced it has been granted orphan drug designation status by the U,S, Food and Drug Administration for mexiletine meant to treat myotonic disorders.

Myotonic disorders are a group of inherited, neuromuscular disorders characterized by a shared symptom called myotonia. Myotonia is an inability to relax a contraction of skeletal muscle which originates from a voluntary muscular contraction such as shaking someone’s hand and blinking, or everyday activities such as walking across a street and climbing stairs.

Mexiletine reduces myotonia symptoms, resulting in a significant improvement in patient quality-of-life and other functional outcomes. The FDA grants the ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S.

“There is a serious unmet medical need for the management of symptoms in patients with myotonic disorders,” said Vinita Gupta, CEO, Lupin “The decision …to grant orphan drug designation to mexiletine brings us closer to providing a licensed treatment option for patients in the U.S.”

Orphan Drug Act

The Orphan Drug Act provides for granting special status to a drug or biological product (“drug”) to treat a rare disease or condition upon request of a sponsor. This status is referred to as orphan designation (or sometimes “orphan status”).

For a drug to qualify for orphan designation both the drug and the disease or condition must meet certain criteria specified in the ODA and FDA’s implementing regulations. Orphan designation qualifies the sponsor of the drug for various development incentives of the ODA, including tax credits for qualified clinical testing.

Myotonic dystrophy (DM) affects multiple systems in the body. The two types of DM (DM1 and DM2) differ in prevalence, affected genes, disease progression, symptoms and severity of symptoms, with sub-classifications based on disease onset, making it difficult to know how the disorder will affect patients.

DM1 is the most common form, with the global consensus that myotonic dystrophies, based upon estimates from the NIH and others for western European and North American populations, affect 12.5 per 100,000 individuals.

Non-dystrophic myotonias (NDM) is caused by mutations within ion channels in the sarcolemma membrane of skeletal muscles and affects 1 in 100,000 people. Non-dystrophic myotonias exhibit both sodium and chloride channelopathies which result in altered membrane excitability.

Affects legs, facial muscles

Unlike DM, for patients with NDM myotonia is the most prominent symptom and demonstrates different phenotypes in subgroups of NDM disorders, and can affect different parts of the body, such as legs, arms or facial muscles, more severely.

Myotonia in NDM patients has an onset in childhood and persists across their lifetime. Patients perceive that myotonia increases in severity over time, impacting daily life. Myotonia is described by patients in a variety of ways (stiffness, cramps, pain, difficulty releasing a fist, or difficulty swallowing or eating) which can contribute to substantial delays in diagnosis and treatment, leading to decreased patient quality-of-life and often significant disability.

Mexiletine (167 to 500 mg/day) in randomized controlled trials in adult patients with non-dystrophic myotonia, has been shown to significantly reduce myotonia compared to a placebo.

This resulted in an improvement in patient quality-of-life and other functional outcomes, with gastro-intestinal discomfort reported as the most common adverse event, demonstrating mexiletine to be safe and well-tolerated in this patient population.

Lupin, headquartered in Mumbai, India, develops and commercializes a wide range of branded and generic formulations, biotechnology products and APIs in over 100 markets in the U.S., India, South Africa and across the Asia Pacific (APAC), Latin America (LATAM), Europe and the Middle-East regions.

The company occupies a leadership position in the cardiovascular, anti-diabetic, and respiratory segments and has a significant presence in the anti-infective, gastro-intestinal (GI), central nervous system (CNS) and women’s health areas. Lupin has fifteen manufacturing sites, seven research centres, more than 20,000 professionals working globally.