CHMP Gives Positive Opinion to Adakveo for Treating Vaso-occlusive Crises in SCD Patients

A European Medicines Agency (EMA) committee has adopted a positive opinion on Novartis‘s Adakveo (crizanlizumab) for the prevention of vaso-occlusive crises (VOCs) in people with sickle cell disease (SCD).

The EMA’s Committee for Medicinal Products for Human Use (CHMP) recommended the conditional approval of Adakveo, alone or in combination with hydroxyurea (hydroxycarbamide), to prevent VOCs, or pain crises, in individuals 16 and older.

“The positive CHMP opinion for Adakveo underscores the potential of this new medicine to prevent recurrent sickle cell pain crises, which can affect all aspects of patients’ lives,” Susanne Schaffert, PhD, president of Novartis Oncology, said in a press release.

If accepted by the European Commission, which makes the final decision based on the CHMP’s recommendation, Adakveo will become the first targeted medication approved in the European Union for preventing VOCs in SCD patients. A decision is expected in about two months.

“Novartis is dedicated to innovation where there is significant unmet need, and we are grateful for the support we have received from the community of sickle cell patients, advocates and medical experts in Europe and around the world who continue to help us reimagine medicine for this devastating disease,” Schaffert said.

SCD is characterized by abnormally shaped red blood cells, from which the disease derives its name. These “sickle-shaped” cells have a tendency to clump and stick together, which can block small blood vessels, resulting in VOC. In SCD, a protein called P-selectin promotes sickle-shaped red blood cells to stick to each other and to the walls of blood vessels, increasing the risk of VOC.

Adakveo is a monoclonal antibody that works by blocking the activity of P-selectin, decreasing the likelihood that cells will clump and cause VOCs. The medication was approved in the U.S. in late 2019.

Both the U.S. approval and the new CHMP opinion were based on the results of the SUSTAIN Phase 2 clinical trial (NCT01895361). The trial enrolled 198 people with SCD, age 16 and up, with a history of frequent VOCs (between two and 10 episodes in the year before starting the study). Most participants (91.9%) were Black or African American.

Participants were assigned randomly to an intravenous infusion of Adakveo at one of two doses (2.5 mg/kg or 5 mg/kg) or a placebo, every other week in the first two doses and then every four weeks for about one year. Most patients (62.1%) received their assigned treatment as an add-on therapy to standard hydroxyurea/hydroxycarbamide, but some (37.9%) received it alone.

The study’s main goal was to evaluate whether Adakveo reduced the frequency of annual VOCs requiring a visit to a medical facility and treatment with either opioids or nonsteroidal anti-inflammatory drugs (NSAIDs) to control pain.

Findings from SUSTAIN showed that treatment with 5 mg/kg Adakveo significantly reduced the annual frequency of VOCs by 45% (1.63 vs. 2.98 for placebo). Annual VOC reductions were seen in participants regardless of their underlying mutation or previous treatment with hydroxyurea.

The higher Adakveo dose also significantly reduced by 42% the length of VOC-related hospitalizations (median four days vs. 6.87 days) and increased the median time to first VOC (4.1 months vs. 1.4 months). Notably, Adakveo nearly doubled the proportion of patients without a VOC event over the study duration (36%), compared to a placebo (17%).

The most common treatment side-effects included joint pain (18%), nausea (18%), back pain (15%), and fever (11%).

“Today’s positive opinion by CHMP means that we are one step closer to potentially having an important new medicine to treat thousands of vulnerable patients,” said Jo Howard, a professor at Guy’s and St Thomas’ NHS Foundation Trust, and a SUSTAIN investigator.

An open-label Phase 2 trial (NCT03474965) now intends to find an appropriate dose of Adakveo in pediatric patients. The trial is currently recruiting infants and children with SCD, age 6 and older, who have had at least one VOC in the past year. Enrollment is ongoing in the U.S., Canada, Europe, and elsewhere; additional information is available here.