EU regulators recommend yanking authorization for Novartis' sickle cell med Adakveo after phase 3 miss

After Novartis’ sickle cell disease medicine Adakveo flopped in a phase 3 trial, European regulators promised to take a closer look at its prior approval. Now, the reexamination has come back with a recommendation to revoke authorization.

The European Medicines Agency’s (EMA's) Committee for Medicinal Products for Human Use (CHMP) recommended snatching back Novartis' approval after concluding that the med’s benefits did not outweigh the risks. The decision was based on the results of the phase 3 STAND trial, in which the drug didn’t outperform placebo.

Specifically, Adakveo (crizanlizumab) couldn’t reduce the number of painful crises leading to a healthcare visit. Adakveo-treated patients saw an average of 2.5 painful crises resulting in a healthcare visit over their first year of treatment, while patients in the placebo group had an average of 2.3.  

Another nail in the coffin was the average number of crises requiring a home healthcare visit or treatment, which was 4.7 in the Adakveo group compared with placebo’s 3.9.

The CHMP also looked at data from other studies including a managed access program and real-world data, which proved futile due to the “several limitations” in the studies including a lack of a comparator, the committee said.

The EMA requested the STAND study with its 2020 marketing authorization due to uncertainty about the limited data available at the time. Now, the European Commission will issue a final decision, which is expected in the next two months, and the drug could be wiped from the market.

Novartis will “continue to coordinate with health authorities globally,” according to a recent statement.

“We maintain our confidence in crizanlizumab as an important treatment option when used to reduce the frequency of sickle cell pain crises, based on the overall body of evidence available to date,” the company added.

Meanwhile, in the U.S., conversations with the FDA are “still ongoing” following the results of the STAND trial, a Novartis spokesperson said over email.

Novartis originally scored the drug through the $665 million Selexys Pharmaceuticals buyout in 2016. Adakveo nabbed FDA approval in 2019 after results showed it could lower the median rate of crises by 45% compared with placebo.

Then in 2021, Adakveo won a nod from England’s National Institute for Health and Care Excellence through a special pathway despite “high uncertainty” about the drug’s long-term efficacy and cost-effectiveness.

Novartis isn’t the only one that chalked up a loss at the CHMP’s May meeting. The committee reconfirmed its original recommendation to deny authorization for Ipsen’s Sohonos, which is intended to treat rare genetic disease fibrodysplasia ossificans progressiva. So far, that drug has only been approved in Canada and received a complete response letter from the FDA in December 2022. An FDA decision is now expected Aug. 16.