New Drugs Turned Down by EU Safety Assessor

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has given negative opinions for two drugs intended to treat amyotrophic lateral sclerosis (ALS) and age-related macular degeneration (AMD). It also recommended nonrenewal of a conditional authorization for a Duchenne muscular dystrophy medication.

ALS Medicine Not Recommended 

At its June 2024 meeting, the CHMP said that it recommended refusal of marketing authorization for masitinib (AB Science), a medicine intended to treat ALS. Its active substance, masitinib mesylate, is a protein kinase inhibitor that blocks enzymes involved in various immune-mediated inflammatory processes. The expectation was that this would reduce inflammation and protect nerve cells from damage, thereby slowing the worsening of ALS symptoms.

Masitinib, which was given orphan drug designation in 2016, is an oral tablet intended to be used in combination with riluzole, a drug indicated to extend life or time to mechanical ventilation in patients with ALS but which has no therapeutic effect on motor function, lung function, fasciculations, muscle strength, or motor symptoms. 

AB Science presented evidence from a trial of 394 adults with ALS treated with masitinib or placebo, both in combination with riluzole, twice daily for 48 weeks. The main measure of effectiveness was the change over 48 weeks in an ALS-specific quality-of-life score. However, the CHMP said, drug benefits could not be convincingly demonstrated. The trial found no difference between the active drug and placebo in the main measure of effectiveness and had several methodological issues that made the data unreliable.

The European Medicines Agency's opinion therefore was that the benefits of masitinib did not outweigh its risks. There are no consequences for patients in ongoing clinical trials with the drug, and the company may ask for reexamination of the opinion within 15 days.

AMD Drug Not Recommended 

The CHMP also did not recommend marketing authorization for Syfovre (pegcetacoplan; Apellis Europe B.V.), a drug intended to treat geographic atrophy secondary to AMD. Geographic atrophy is an advanced form of dry AMD in which lesions form in the retina and macula, causing large, well-demarcated sections of the retina to stop functioning, leading to irreversible loss of vision.

With geographic atrophy, the complement system is overactive, leading to inflammation and cell death in the retina. The drug's active substance is pegcetacoplan, which is injected into the eye as a solution. It works by blocking the C3 protein of the complement system, thus preventing complement activation and slowing the growth of atrophic lesions.

The company presented results from two main trials involving 1258 adults with AMD and geographic atrophy. Pegcetacoplan injections were compared with sham procedures, and any changes in lesion size were examined 12 months later.

The CHMP said that although the results showed that pegcetacoplan did slow the growth of lesions, this did not lead to clinically meaningful benefits for patients. Given the risks of regular injections into the eye, the CHMP said that a positive balance of benefits and risks could not be established, and it recommended refusing marketing authorization.

Again, there are no consequences for patients taking the drug as part of a clinical trial, and the company may ask for reexamination of the opinion within 15 days of receiving it.

Conditional Authorization for Translarna Not Recommended for Renewal

The CHMP also recommended not renewing the conditional marketing authorization for Translarna (ataluren; PTC Therapeutics), a medicine for treating some patients with Duchenne muscular dystrophy.

Translarna is used in patients whose disease is caused by a nonsense mutation in the dystrophin gene and who are still able to walk. An initial negative opinion on the renewal of its marketing authorization was given last September and was confirmed in January this year, following a reexamination requested by the company. The CHMP said that following reevaluation of the drug's benefits and risks, both rounds of assessment had concluded that Translarna's effectiveness had not been confirmed.

Last month, the European Commission had asked the CHMP to further consider whether new data from a scientific advisory group on neurology convened in March this year affected its conclusions on the medicine's benefit-risk balance. Further publications were reviewed, along with input from parents or caregivers of boys affected by Duchenne muscular dystrophy, patient organizations, healthcare professional organizations, and treating doctors, as well as reports on individual patients treated with Translarna.

The CHMP concluded, after a thorough assessment of the totality of the data, that despite the high unmet medical need for an effective treatment for patients with this rare disease, there was still insufficient evidence to confirm Translarna's effectiveness. Therefore, the benefit-risk balance was negative and the CHMP recommended not renewing its marketing authorization in the EU.

This opinion will now be forwarded to the European Commission for a final legally binding decision applicable in all EU member states.