Adakveo®

Update: 19 December 2024

Data presented at the 66^th ASH Annual Congress (7 – 10 December 2024) in San Diego (USA) showed that:

• Interim analysis of SOLACE-Kids (an ongoing phase 2 study to assess dosing and evaluate safety in paediatric patients with SCD) confirmed an optimum dosage of 8.5mg/kg for patients aged 6 – 12 years with SCD.
• Crizanlizumab was safe and well tolerated, consistent with results of the adult trials, in the 53 patients treated by the cut-off date of 2 March 2023.

Source: Pharmacokinetics/Pharmacodynamics, Safety, and Efficacy of Crizanlizumab in Patients with Sickle Cell Disease Aged 6 to <12 Years: 2-Year Data from the Phase 2 Solace-Kids Study

Update: 30 September 2024

No update available.

Update: 30 June 2024

No update available.

Update: 31 March 2024

MHRA (UK) has revoked the conditional marketing authorisation for Adakveo after an internal review concluded the drug was not sufficiently effective as it failed to meet the goals set by the STAND trial (NCT03814746) that had been launched to confirm the drug’s effectiveness as part of the full approval process in the UK.

Therefore the review process noted that the drug failed to reduce the annual rates of VOCs in SCD patients and hence did not confirm its clinical benefit. At least 200 patients in the UK were being treated with Adakveo, testifying that symptoms were alleviated.

Sources: https://www.independent.co.uk/news/health/sickle-cell-treatment-b2477056.html
https://www.pharmaceutical-technology.com/news/mhra-revokes-authorisation-novartis-adakveo/
https://sicklecellanemianews.com/news/conditional-approval-adakveo-sickle-cell-drug-now-revoked-uk/

Update: 20 December 2023

New data:

Data presented at the 65^th ASH Annual Congress (9–12 December 2023) in San Diego (USA) showed that:

• • Crizanlizumab did not demonstrated superiority over placebo (phase 3, STAND Trial – NCT03814746). This may be due to a variety of factors, e.g. geographic differences in healthcare services, patient selection with less severe disease, etc.
  • The safety profile of crizanlizumab 5mg dose from the pooled data of  3 Phase 2 studies (SUSTAIN [NCT01895361], SOLACE-adults [NCT03264989], and the pediatric SOLACE-Kids [NCT03474965]) and 1 Phase 3 study (STAND [NCT03814746]) in patients with SCD, showed no new safety concerns. Most adverse reactions were mild, and discontinuation due to adverse reactions was infrequent.

Sources: https://www.hematologyadvisor.com/home/conference-coverage/ash-2023/crizanlizumab-scd-patients-demonstrates-no-significant-benefit/
https://ash.confex.com/ash/2023/webprogram/Paper188639.html

Update: 30 September 2023

The European Commission has revoked conditional Marketing Authorisation for Adakveo following a review by the EMA’s Committee for Medicinal Products for Human Use (CHMP) and relevant  recommendation.

Source: https://www.europeanpharmaceuticalreview.com/news/185654/european-commission-revokes-marketing-authorisation-for-novartis-crizanlizumab/

Update: 30 June 2023

No update available.

Update: 31 March 2023

Preliminary results from the ongoing global Phase III STAND study in sickle cell disease showed no difference between Adakveo and placebo in annual rates of vaso-occlusive crises leading to a healthcare visit over the first-year post randomization.

Consequently, the EMA’s Committee for Medicinal Products for Human Use (CHMP) has started a review of Adakveo to evaluate the impact of these results on its currently authorized use.

Adakveo was approved in the USA in November 2019 for the reduction in frequency of vaso-occlusive crises. In October 2020, the European Medicines Agency’s (EMA) granted conditional Marketing Authorization to prevent recurrent vaso-occlusive crises in patients aged 16 years and above, living with sickle cell disease.

Sources: https://www.thepharmaletter.com/article/ema-s-chmp-reviewing-adakveoauthorization-after-trial-failure
https://www.fiercepharma.com/pharma/novartiss-adakveo-couldnt-beat-placeboema-review-its-current-authorization