EMA Recommends Revocation of Authorization for Sickle Cell Disease Medicine Adakveo

EMA Recommends Revocation of Authorization for Sickle Cell Disease Medicine Adakveo

Rare Daily Staff

The European Medicines Agency’s committee for medicinal products for human use (CHMP) has recommended revoking the marketing authorization for Novartis’s Adakveo, a medicine for preventing painful crises called vaso-occlusive crises in patients aged 16 years and older with sickle cell disease.

The recommendation follows a review by the CHMP, which concluded that the benefits of the medicine did not outweigh its risks. The review looked at results of the STAND study, which compared the effectiveness and safety of Adakveo with placebo in patients who had previously had painful crises leading to a healthcare visit.

The study showed that Adakveo did not reduce the number of painful crises leading to a healthcare visit. Patients treated with Adakveo had on average 2.5 painful crises with a subsequent healthcare visit over the first year of treatment, compared with 2.3 crises in the placebo group.

In addition, the average number of crises requiring a healthcare visit or treatment at home was 4.7 with Adakveo compared with 3.9 with placebo.

People with sickle cell disease (SCD) have a mutation that alters hemoglobin, the protein in red blood cells that carries oxygen to cells throughout the body. The sickle mutation causes red blood cells to have an abnormal sickle or crescent shape, which makes them inefficient in their oxygen-carrying capacity and leads to chronic anemia, vaso-occlusive crises with severe pain, multi-organ damage, complications like stroke, and a shortened life expectancy.

In its review, the CHMP also looked at data from other studies, a managed access program and real‑world data. However, the studies had several limitations, such as the lack of a comparator, and could not be used to show the effect of Adakveo or counterbalance the negative results of the STAND study.

In terms of safety, the STAND study did not raise new concerns but showed a higher rate of severe and serious treatment-related side effects for Adakveo compared with placebo. The CHMP therefore concluded that its benefits do not outweigh the risks.

At the time of marketing authorization, data showed that Adakveo was effective at reducing the number of painful crises in patients with sickle cell disease. However, the data were limited and there was some uncertainty about the size of the medicine’s effect.

EMA therefore requested the STAND study as a condition for the marketing authorization of Adakveo, which was granted in October 2020. As the STAND study results do not confirm the benefits previously seen with Adakveo, the CHMP has now concluded that the benefits do not outweigh the risks and recommended the revocation of its authorization in the EU.

Following the CHMP’s recommendation, the European Commission will issue a legally binding decision.