AstraZeneca has finally won over the US Food and Drug Administration (FDA) with its immunotherapy Imjudo (tremelimumab), winning approval from the agency for use in combination with the company’s programmed death-ligand 1 (PD-L1) inhibitor Imfinzi (durvalumab) for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer.
The FDA clearance is the first for tremelimumab, which faced an uphill battle after having suffered several failures in trials for other cancer types over the past two decades of its development, including non-small cell lung cancer, head and neck cancer and bladder cancer.
According to a press release from AstraZeneca announcing the approval, liver cancer is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide. Approximately 36,000 new cases of the cancer are diagnosed each year and it is the fastest-rising cause of cancer-related deaths in the US.
About 75 percent of all primary liver cancers in adults are HCC. Additionally, chronic liver diseases are associated with inflammation that over time can lead to the development of HCC.
Imjudo is an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) monoclonal antibody that blocks the action of CTLA-4. Inhibition of the protein aids in T-cell activation to prime the immune system against cancer cells to induce their death.
Imjudo is administered as a single dose with Imfinzi, followed by Imfinzi infusions every four weeks.
Imjudo’s approval was based on results from the HIMALAYA Phase III trial, which showed that patients treated with the Imjudo and Imfinzi combination experienced a 22 percent reduction in the risk of death versus sorafenib. Additionally, after three years, 31 percent of patients treated with the combination were still alive compared with 20 percent of patients treated with sorafenib.
While the results are positive, they don’t quite measure up to Roche’s PD-L1 blocker Tecentriq and anti-vascular endothelial growth factor (anti-VEGF) drug Avastin combo, which together have been shown to cut the risk of death by 42 percent in trials. Tecentriq and Avastin have become the new standard of care for newly diagnosed liver cancer, making it a competitive market for Imjudo and Imfinzi.
Nevertheless, the new drug combination offers another promising option for liver cancer treatment. And it is a unique, first-of-its-kind option as it is the first FDA-approved liver cancer treatment to feature two immunotherapies.
“With this first regulatory approval for Imjudo, patients with unresectable liver cancer in the US now have an approved dual immunotherapy treatment regimen that harnesses the potential of CTLA-4 inhibition in a unique combination with a PD-L1 inhibitor to enhance the immune response against their cancer,” said Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca.
Fredrickson also said the target patient population for Imfinzi-Imjudo are patients who aren’t eligible to receive an anti-VEGF agent.
Another plus is Imfinzi-Imjudo’s safety profile, as investigators saw no increase in severe liver toxicity or bleeding risk. The safety profile of the combination of the two was consistent with the known profiles of each drug alone, with no new safety signals identified.
This is better than Bristol Myers Squibb’s combo of Opdivo (PD-1 inhibitor) and Yervoy (CTLA-4 inhibitor), which in the trial based on the treatment’s approval, involved 14 percent of patients dropping out due to incidences of intestinal inflammation, and treatment was withheld from four percent of patients due to similar issues. In comparison, only one percent of patients that received Imjudo in trials had to discontinue the drug due to intestinal problems.
AstraZeneca said that based on the HIMALAYA trial results, regulatory applications for Imjudo in combination with Imfinzi are currently under review in Europe, Japan and several other countries for the treatment of patients with advanced liver cancer.
The Imfinzi-Imjudo combination was approved under FDA priority review.
AstraZeneca is currently conducting late-stage trials of Imjudo in bladder cancer while academic centers are evaluating it in ovarian, prostate and head and neck cancers.
The company said it will disclose Imjudo’s price in the next couple of days.
As a comparison, Bristol Myers Squibb’s CTLA-4 inhibitor Yervoy is priced at just over $33,000 for a four-injection treatment plan. The drug is approved in seven different types of cancer and the sales hit $2 billion in 2021 from $1.7 billion in 2020, an increase of 20 percent.