Withdraw marketing of Durvalumab for metastatic urothelial carcinoma: CDSCO panel tells AstraZeneca

New Delhi: In a major setback to AstraZeneca Pharma India Limited., the Subject Expert Committee (SEC) of the Central Drugs Standard Control Organisation (CDSCO) has rejected the drug maker's proposal, suggesting the firm to withdraw marketing of Durvalumab inj. for infusion of 120 mg/2.4 mL or 500 mg/10 mL for the metastatic urothelial carcinoma indication with immediate effect.

This came in the wake of the proposal presented by AstraZeneca Pharma India for continued use of the approved indication for metastatic Urothelial Carcinoma in light of the outcome of the Phase-III clinical trial.

However, the committee noted that the drug was granted conditional accelerated approval by the US FDA subject to the conduct of post-marketing clinical studies and the successful outcome of the confirmatory DANUBE study. The drug failed to meet its co-primary endpoints in the clinical study. Consequently, the firm withdrew marketing of the drug for the said indication in the USA. Further, the indication is not approved in the EU.

Durvalumab, a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, is a novel immune-checkpoint inhibitor for cancer treatment. It is a programmed death-ligand 1 (PD-L1) blocking antibody that helps to enhance normal immune responses that attack tumour cells. Durvalumab, marketed under the trade name Imfinzi, was developed by Medimmune/AstraZeneca. It is available for intravenous injections.

The FDA granted Durvalumab accelerated approval in May 2017 for the treatment of individuals with locally advanced or metastatic urothelial cancer. However, in the clinical trial, the medication failed to meet its co-primary objectives. As a result, the company has stopped marketing the medication in the United States for that use. Furthermore, the indication is not approved in the European Union.

Durvalumab used in combination with etoposide and either carboplatin or cisplatin was approved as a first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC) by the FDA on March 27, 2020.

AstraZeneca Pharma India's proposal to continue use of Durvalumab inj. for the approved indication of metastatic Urothelial Carcinoma was thoroughly examined by the committee at the 110th SEC meeting for Oncology & Haematology, held on 13.07.2021 & 14.07.2021 at CDSCO.

Responding to AstraZeneca Pharma India's proposal, the committee opined that the subject indication was granted approval in India based on the accelerated approval of the US FDA and, therefore, continued marketing should be examined based on the regulatory status of the drug in the USA.

After detailed deliberation, the committee recommended the firm should withdraw marketing of the product for the metastatic urothelial carcinoma indication with immediate effect.

However, the committee also stated that the drug may continue to be marketed for other approved indications.