India's Drug Regulator Recommends Discontinuation of Crizanlizumab Following Failed Efficacy Trial
核心洞察
India's Subject Expert Committee (搜索) has recommended discontinuing import and marketing permission for crizanlizumab (Adakveo) for sickle cell disease (搜索) treatment, following the European Medicines Agency (搜索)'s 2023 withdrawal decision.
The recommendation stems from the STAND phase III study's failure to demonstrate statistically significant differences between crizanlizumab and placebo in reducing vaso-occlusive crises (搜索) in sickle cell patients.
Despite no new safety concerns emerging from global post-marketing and phase IV data, the committee concluded that efficacy evidence remains inconclusive for the intended indication.
India's Subject Expert Committee (搜索) (SEC) has recommended discontinuing the import and marketing permission for crizanlizumab (Adakveo), a treatment for sickle cell disease (搜索), following regulatory actions by international agencies based on failed efficacy data. The decision aligns with the European Medicines Agency (搜索)'s withdrawal of conditional marketing authorization in August 2023.
Regulatory Action Based on Failed Phase III Trial
The SEC's recommendation centers on the results of the STAND phase III study, which failed to demonstrate significant therapeutic benefit. According to the committee's assessment, "the STAND study did not demonstrate a statistically significant difference between crizanlizumab 5mg/kg or crizanlizumab 7.5mg/kg and placebo in annualized rates of vaso-occlusive crises (搜索) leading to a healthcare visit over the first-year post randomization."
The EMA's Committee for Medicinal Products for Human Use (CHMP) initially recommended revoking the conditional marketing authorization on May 26, 2023, leading to the formal withdrawal on August 3, 2023. This decision is legally binding across all 27 European Union countries.
Indian Regulatory Review Process
The crizanlizumab concentrate for solution for infusion 10 mg/mL (100 mg/10 mL) was originally approved for Sandoz in India on March 26, 2020, with a phase III waiver. Following the EMA's action, the company presented ongoing study status on March 5, 2024, and was requested to submit interim safety and efficacy data from the ongoing phase IV study in India.
During the SEC meeting on August 19, 2025, Sandoz presented the final Clinical Study Report of their phase IV clinical trial titled "An Indian Multi-centric phase IV study to assess the safety of crizanlizumab with or without hydroxyurea therapy in sickle cell disease (搜索) patients with vaso-occlusive crises (搜索)."
Safety Profile Remains Acceptable
The committee noted that "no new significant safety concerns had emerged from the available global post-marketing and phase IV data." The STAND study also did not suggest new safety concerns with the drug. However, the SEC concluded that "the efficacy of the product for the intended indication remains inconclusive based on the currently available evidence, including the EMA/CHMP assessment report."
Global Regulatory Impact
The regulatory challenges extend beyond Europe and India. The UK's Medicines and Healthcare products Regulatory Agency (MHRA) also revoked the conditional marketing authorization for crizanlizumab in January 2024, further limiting the drug's global availability.
Treatment Administration and Corporate Changes
Adakveo is administered as a 30-minute IV infusion for patients 16 years and older with sickle cell disease (搜索) to reduce the frequency of painful crises. The treatment protocol involves an initial infusion, followed by a second infusion two weeks later, then monthly maintenance infusions.
The company informed the SEC that crizanlizumab is currently not launched and is being imported into India. Notably, while Sandoz Pvt Ltd submitted the application to the SEC, Adakveo is branded by Novartis in countries like the US, and Novartis completed the spin-off of Sandoz by October 2023.
The SEC's final recommendation states that "the import and marketing permission granted vide no. IMP/BIO/20/000026 dated 26-Mar 2020 of the drug product may be discontinued until adequate data establishing the efficacy and favourable benefit-risk profile of the product are made available."