Two treatments for rare genetic diseases have been granted approval this month by the European Medicines Agency (EMA).
Amyotrophic Lateral Sclerosis
The agency recommended granting a marketing authorization in the European Union (EU) for tofersen (Qalsody) for adult patients with the rare motor neuron disease amyotrophic lateral sclerosis (ALS).
Patients with ALS experience nerve cell deterioration in the brain and spinal cord resulting in increasing loss of muscle function and paralysis of voluntary muscles, including respiratory muscle, which ultimately leads to respiratory failure. The mean survival for patients with ALS is 2-5 years.
Tofersen is an antisense oligonucleotide that binds to the mRNA of the SOD1 gene to reduce the production of Sod1 protein. The medicine is expected to improve the symptoms of ALS by reducing the amount of defective Sod 1 protein. It is indicated for the treatment of adults with ALS who have a SOD1 mutation.
The committee considered clinical data from a 2-week randomized study involving 108 patients aged 23-78 years who had weakness attributable to ALS and laboratory-confirmed SOD1 mutation. Results published in The New England Journal of Medicine in September 2022 demonstrated reductions of approximately 60% in plasma neurofilament light chain concentrations in patients who received tofersen compared with the placebo group, suggesting reduced neuronal injury. Improvements were also noted in the physical abilities of patients who received tofersen compared with those who received placebo.
The EMA's Committee for Medicinal Products for Human Use (CHMP) decided to authorize tofersen in exceptional circumstances, a route available wherein the data are incomplete because patient numbers are limited or there are gaps in the scientific knowledge. The manufacturer, Biogen Netherlands, has been asked to submit further data to the EMA on the drug's long-term efficacy and safety.
Tofersen is available as a 100-mg solution for injection and is given intrathecally by lumbar puncture. The most common side effects are pain, fatigue, pyrexia, arthralgia, myalgia, and increased levels of white blood cells and proteins in the cerebrospinal fluid.
Paroxysmal Nocturnal Hemoglubinuria
At its February meeting, the CHMP also gave a positive opinion on danicopan (Voydeya) for treating residual hemolytic anemia in patients with paroxysmal nocturnal hemoglobinuria (PNH).
PNH is a rare genetic disorder and potentially life-threatening blood disease leading to hemolytic anemia , with symptoms manifesting as fatigue, body pain, blood clots, bleeding, and shortness of breath.
The active substance of danicopan is danicopan, a complement inhibitor that reversibly binds to factor D to prevent alternative pathway-mediated hemolysis and deposition of complement C3 proteins on red blood cells.
The committee largely based its decision to grant a marketing authorization for danicopan on results from a randomized, double-blind, placebo-controlled phase 3 study involving 86 patients with PNH and clinically significant evidence of residual hemolytic anemia while being treated with C5 complement inhibitors ravulizumab or eculizumab. Trial results indicated a clinically relevant increase in hemoglobin for those treated with danicopan compared with those treated with placebo. Patients also benefited from a significant decrease in fatigue and the number of required blood transfusions.
Danicopan will be available as 50-mg and 100-mg tablets. The most common side effects are pyrexia, headache, increased hepatic enzyme levels, and pain in the extremities.
Danicopan was considered for marketing authorization through the EMA's Priority Medicines scheme for medicines with the potential to address patients' unmet needs.