Biogen has announced plans to evaluate a higher dose of its spinal muscular atrophy (SMA) drug Spinraza (nusinersen) in a new Phase II/III clinical trial called DEVOTE.
Spinraza is an antisense oligonucleotide (ASO) that increases the amount of full-length survival motor neuron (SMN) protein. It is indicated to treat infants, children and adults with SMA in more than 40 countries.
DEVOTE will investigate the potential of a higher dose of the drug to offer greater efficacy in a wide patient population. The trial will also examine the drug’s safety and tolerability at a higher dose.
The global, dose-escalating, three-part study is expected to enrol 126 patients of all ages at 50 sites.
It will comprise an open-label safety assessment, along with a pivotal, double-blind, active control randomised treatment period and an open-label treatment period.
The safety assessment will be followed by a comparison of two 50mg loading doses given 15 days apart. Patients will subsequently receive a 28mg maintenance dose every four months.
The existing schedule approved by the US Food and Drug Administration (FDA) involves four loading doses with 12mg maintenance doses every four months.
The open-label evaluation part of the trial will establish a safe and efficient approach to switch patients from the currently approved dose to the investigational higher dose.
Biogen executive vice-president and chief medical officer Alfred Sandrock said: “Spinraza has fundamentally changed the natural history of SMA. Antisense oligonucleotides directly intervene at the origin of disease providing a transformative therapeutic option.
“Spinraza’s highly targeted approach and well-characterised safety profile allows us to continue exploring ways to potentially address the remaining medical needs in the SMA community.”
The company also reported new data from an integrated analysis of an open-label extension study, SHINE, which recruited previous participants of Spinraza studies.
Data revealed improvements or stabilisation in one or more motor function measures for up to six years in children who had later-onset SMA. This contradicts the expected decline found in natural history cohorts.