AstraZeneca Voluntarily Withdraws Checkpoint Inhibitor Approved for Bladder Cancer Indication

AstraZeneca has finally decided to voluntarily wrap up its Imfinzi business for bladder cancer after the med fell short in a confirmatory trial. Imfinzi is an anti-PD-L1 checkpoint therapy that showed remarkable efficacy in shrinking bladder cancer in a Phase ½ clinical trial. This led to an accelerated approval from the FDA four years ago. However, it came with one condition—the drug remains approved only if it sustains similar efficacy in a larger Phase 3 trial.

Unfortunately, Phase 3 results show that patients who took Imfinzi or its combination with tremelimumab have failed to meet the primary endpoint of extending median survival of patients as compared the standard-of-care chemotherapy. Although AstraZeneca observed improvement in patients with high PD-L1 expressing tumors, it has still decided to shut the program completely following discussions with the FDA.

Nevertheless, the company believes that this is not a setback as most of its revenue comes from the non-small cell lung cancer indication. Additionally, it is planning to expand the usage of the drug in other bladder cancer indications solo or in combination with tremelimumab. If approved, it can recover the loss for Imfinzi’s current retraction. Three trials are running currently that are either in the early-or late-stage settings. It includes the NILE Phase 3 trial in metastatic disease, the NIAGARA Phase 3 trial in muscle-invasive disease, and the POTOMAC Phase 3 trial in non-muscle invasive disease.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said, “The science of immunotherapy has moved swiftly over the past few years, bringing new options to patients at an unprecedented pace. While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded and remain committed to bringing new and innovative options to patients. In the last three years, Imfinzi has become an important standard of care in multiple lung cancer settings, an area of considerable focus for AstraZeneca.”

Currently Available Treatments

Bladder cancer is considered one of the most aggressive cancers worldwide, with an estimated 76,960 new cases each year in the US alone. Traditionally, first-line therapy for bladder cancer was based on cisplatin combinations. However, nearly all patients ultimately progressed and died from cancer despite the initial response to the therapy.

Immune checkpoint inhibitors have become an increasingly used therapeutic option in many solid tumors, including bladder cancer. Many, including Keytruda, Nivolumab, Atezolizumab, Durvalumab, and Avelumab, have been approved as first-line therapy in case of bladder cancers that are unresponsive to cisplatin.

However, the indication has been difficult to crack. Merck and Co.’s Keytruda, which currently has conditional approval, could not alone or in combination stop the disease progression or increase the lifespan of bladder cancer patients compared to chemotherapy. After noticing some treated patients performing worse than chemo, the FDA decided to narrow Keytruda’s usage to only those who have a high expression of the marker the therapy targets. Roche experienced the same with Tecentriq, which failed to fend off tumor progression in Phase 3 Imvigor010 trial in muscle-invasive bladder cancer patients after surgery.

A Long Line of Retractions

AstraZeneca isn’t the first one to withdraw an immunotherapy drug after it failed in late trials. Late last year, Bristol Myers Squibb retracted Opdivo for late-stage small cell lung cancer. Similar to Imfinzi, Bristol’s drug alone or in combination with CTLA4 inhibitor Yervoy failed in late trials. Roche’s withdrawal of the application to the European Medicines Agency for the use of Tecentriq in combination with chemotherapy as a first-line bladder cancer treatment closely followed. After the failure of the Keynote-361 trial, Merck’s conditional approval of Keytruda is also in danger, and it can soon meet a similar fate.

Related Article: Bavencio Bags FDA Approval as First-line Maintenance Treatment for Urothelial Carcinoma

References

1. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/voluntary-withdrawal-imfinzi-us-bladder-indication.html

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Author

Ruchi Jhonsa