An AstraZeneca antibody drug is now approved for treating liver cancer, a long-awaited regulatory win that follows clinical trial stumbles for the immunotherapy in other types of cancer. The FDA decision makes the AstraZeneca drug just the second immunotherapy approved to go after one cancer target in particular.
The new AstraZeneca drug, tremelimumab, is approved for treating adults who have hepatocellular carcinoma, the most common type of liver cancer. The decision covers advanced cases that cannot be addressed by surgery. Cambridge, U.K-based AstraZeneca will market its new medicine under the name “Imjudo.”
Imjudo belongs to a class of cancer drugs called checkpoint inhibitors, therapies that block proteins that keep immune cells from recognizing and targeting tumors. The new AstraZeneca drug is designed to block a checkpoint protein called CTLA-4, which is found on immune cells. FDA approval of the drug covers its use alongside Imfinzi, an already approved AstraZeneca checkpoint inhibitor that addresses a different protein, PD-L1, which is expressed on cancer cells.
With its FDA approval, Imjudo now joins blockbuster Bristol Myers Squibb drug Yervoy as the only FDA-approved therapies that target CTLA-4. First approved in 2011 for advanced melanoma, Yervoy has gone on to win additional FDA nods for other types of cancer, including liver cancer. That 2020 decision covers the use of Yervoy in combination with BMS drug Opdivo, a checkpoint inhibitor that targets the PD-1 protein on T cells.
The FDA’s Imjudo approval is based on the results of an open-label study enrolling 782 patients randomly assigned to receive either Imjudo and Imfinzi; Imfinzi alone; or sorafenib, a standard treatment for liver cancer. The Imjudo and Imfinzi arm met the main study goal of showing a statistically significant improvement in overall survival, a measure of how long patients lived from the time participants were randomized until death by any cause. In results published in June in the New England Journal of Medicine, 30.7% of those treated with the Imjudo and Imfinzi combination were still alive after three years compared with 20.2% of those given sorafenib.
AstraZeneca persevered with Imjudo despite clinical trial setbacks. In 2017, a test of the drug as a monotherapy and in combination with Imfinzi failed to beat chemotherapy in a Phase 3 study in advanced lung cancer. AstraZeneca tried again in other cancers. In 2020, the pairing of Imjudo and Imfinzi failed a pivotal test in advanced bladder cancer.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
In liver cancer, Imjudo is given under a novel dosing schedule dubbed STRIDE, which stands for single tremelimumab regular interval durvalumamab (Imfinzi). At day one, the infused Imjudo is given as a single 300 mg dose added to a 1500 mg dose of Imfinzi. Patients then receive a 1500 mg dose of Imfinzi every four weeks. Patients continue to receive Imfinzi by itself every four weeks until the disease progresses or the drug’s toxicity becomes unacceptable.
The most common adverse effects reported from the study were rash, diarrhea, fatigue, itching, and muscle and abdominal pain. AstraZeneca said the safety of Imjudo plus Imfinzi, and for Imfinzi alone, were consistent with the known profiles of each drug and the studies turned up no new safety signals.
Regulatory submissions for the Imjudo and Imfinzi drug combination in liver cancer are still under review in Europe, Japan, and several other countries.
Photo: Christopher Furlong, Getty Images
