Taldefgrobep alfa granted orphan drug designation for spinal muscular atrophy in the EU

2nd August 2023

Taldefgrobep alfa has been given orphan medicinal product designation from the European Commission (EC) for the treatment of spinal muscular atrophy (SMA).

A novel anti-myostatin adnectin, the drug has the potential to deliver significant benefits for people with SMA by enhancing muscle function when used in combination with currently available disease modifying therapies that help preserve motor neurons.

Myostatin is a naturally occurring protein that limits skeletal muscle growth and the inhibition of the protein is a promising therapeutic strategy for SMA.

Taldefgrobep alfa’s novelty in a field of myostatin inhibitors is based on its unique, dual mechanism of action. It binds to myostatin to lower overall myostatin levels and also functions as a receptor antagonist, thereby blocking myostatin signalling in skeletal muscles.

The first treatment to be approved by the EU for SMA was nusinersen back in 2017, which was administered via an intrathecal injection. The first oral therapy, risdiplam (brand name Evrysdi) was approved in 2021.

Expressing his delight about the orphan drug designation, Irfan Qureshi, chief medical officer at Biohaven, said: ‘Children and adults living with SMA experience significant muscle weakness and functional impairments affecting their quality of daily life, and a substantial unmet medical need persists. We are excited about the potential for taldefgrobep alfa to improve the lives of patients and families affected by SMA.‘

Biohaven is currently enrolling a Phase 3 clinical trial of taldefgrobep alfa to evaluate its efficacy and safety in participants with SMA.

Taldefgrobep alfa previously received fast track and orphan drug designation in the US.

Spinal muscular atrophy prevalence

SMA is a rare, genetic neurodegenerative disorder characterised by the loss of motor neurons, atrophy of the voluntary muscles of the limbs and trunk, and progressive muscle weakness that is often fatal. Typically diagnosed in young children, the condition is caused by insufficient production of the survival of motor neuron (SMN) protein, which is essential for the survival of motor neurons, and encoded by two genes: SMN1 and SMN2. The condition affects approximately one in 10,000 live births globally, with an estimated incidence in Europe ranging from one in 3,900 to one in 16,000 live births.

Orphan drug designation is only permitted for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating and where the prevalence in the EU is less than five in 10,000 and where the medicine offers significant benefit to those with the condition.