AstraZeneca pulls Imfinzi in bladder cancer, nearly one year after Phase 3 miss

AstraZeneca is withdrawing U.S. marketing of Imfinzi in bladder cancer after the drug failed a study required as a condition of its 2017 accelerated approval. The drug’s other approvals in lung cancer are not affected.

Urinary system, bladder, kidney


AstraZeneca’s immunotherapy Imfinzi is a blockbuster drug but it won’t be generating U.S. sales in bladder cancer anymore. The British pharmaceutical giant is pulling the product from the market in that indication, a decision that follows the drug’s failure in a large study required to retain its approval status.

The withdrawal does not affect Imfinzi’s marketing outside of the U.S., nor does it have any bearing on the drug’s FDA approvals in lung cancer.

Imfinzi is a so-called “checkpoint inhibitor,” a type of cancer immunotherapy that works by blocking PD-L1, a protein found in abundance on the surface of tumors. This protein prevents T-cells from recognizing the cancer. Blocking PD-L1 frees T-cells to seek out and kill cancer cells.

Imfinzi won its first FDA nod in 2017 as a treatment for patients whose urothelial carcinoma, the most common type of bladder cancer, had advanced or spread following chemotherapy. The decision also covered those whose cancer had progressed within 12 months of receiving chemotherapy before or after surgery.

The 2017 decision was an accelerated approval based on Phase 1/2 clinical data—less than the standard Phase 3 data that is typically required for a drug review. Companies who get this quicker path to the market must conduct additional clinical studies in order to confirm the drug’s benefit. Last March, AstraZeneca reported Phase 3 data showing its drug, given by itself or as part of a combination treatment, failed to beat the standard of care chemotherapy in improving how long bladder cancer patients lived.

The FDA has procedures for removing a drug from the market if it fails to show patient benefit in a confirmatory study. But AstraZeneca said Monday that its decision to withdraw Imfinzi is voluntary and was done after consulting with the regulator.

Imfinzi is still authorized in the U.S. for two other indications. In 2018, the FDA approved the drug as a treatment for non-small cell lung cancer that cannot be removed by surgery. Last year, the regulator approved the drug, in combination with chemotherapy, as a treatment for extensive-stage small cell lung cancer.

The U.S. accounted for nearly $1.2 billion of Imfinzi’s more than $2 billion in global sales last year, according to AstraZeneca’s 2020 annual report. But the company has run into hurdles trying to expand use of that drug to other cancers. Two weeks ago, AstraZeneca reported that the drug failed a Phase 3 study in recurrent or metastatic head and neck cancer. In a prepared statement, Dave Frederickson, executive vice president of the company’s oncology business unit, said that the company remains committed to bringing new and innovative treatment options to patients, adding that Imfinzi has become a standard treatment in lung cancer.

AstraZeneca isn’t the only big pharma company that has fallen short in urothelial carcinoma. Merck had tested its blockbuster immunotherapy, Keytruda, as a potential first-line treatment for that indication after surgery, only to fail in a Phase 3 clinical trial last year. But Bristol Myers Squibb still hopes to make its mark in urothelial carcinoma. Last September, the company reported encouraging interim data from a Phase 3 study in muscle-invasive urothelial cancer.

Meanwhile, Seagen is co-marketing a urothelial cancer drug developed in partnership with Astellas Pharma. The antibody drug conjugate, Padcev, was awarded accelerated approval in 2019 for treatment of advanced or metastatic urothelial cancer in patients who have previously received a checkpoint inhibitor and chemotherapy.

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