The FDA expanded Enhertu’s approval to encompass advanced solid tumors positive for the HER2 cancer protein, regardless of tumor type. Analysts say the regulatory decision paves the way for similar broader approvals of other medications in the ADC cancer drug class.The AstraZeneca and Daiichi Sankyo targeted cancer drug Enhertu is now the first therapy in its class approved for treating solid tumors regardless of either the cancer type or where the disease started in the body.
Enhertu had previously won FDA approvals for treating certain advanced cases of breast, gastric, and lung cancers that express a protein called HER2. Late Friday, the FDA expanded the drug’s approval to broadly include the treatment of adults who have HER2-expressing solid tumors. These patients must have a cancer that cannot be removed surgically or has advanced following a prior systemic treatment. The expanded approval came nearly two months ahead of the May 30 target date for a regulatory decision.
Enhertu belongs to the class of therapies called antibody drug conjugates. These therapies are made by linking a targeting antibody to a toxic drug payload in order to deliver a precise strike to tumors. The latest FDA decision for Enhertu is based on the results of three Phase 2 studies that evaluated the ADC in 192 adults. One of the studies was a pan-tumor study that evaluated the drug in six types of solid tumors as well as a seventh group of patients encompassing rare tumor types. Preliminary data from this study were presented last June during the annual meeting of the American Society of Clinical Oncology. The other two Phase 2 tests enrolled patients with non-small cell lung cancer and colorectal cancer.
The main goal for all three studies was measuring the confirmed objective response rate. The studies also assessed the duration of response. In the pan-tumor study, the overall response rate was 51.4% and the median duration of response was 19.4 months. In the lung study, the overall response rate was 52.9%; the median duration of response was 6.9 months. The colorectal cancer study posted a 52.9% overall response rate and a median 5.5 month duration of response.
The most common adverse reactions reported in the clinical trials included lower levels of white blood cells, platelets, and hemoglobin, all of which are already listed as known side effects of Enhertu. The drug’s label includes a black box warning that specifically flags the potential for interstitial lung disease as well as fetal harm when used by pregnant individuals, both risks that were already on the Enhertu label.
The latest regulatory decision for Enhertu, based solely on Phase 2 data, is an accelerated approval. Such approvals typically require companies to conduct post-marketing clinical testing to gather additional data that confirms the safety and efficacy of a drug. In its announcement of the approval, AstraZeneca acknowledged the additional testing requirement but disclosed no details about confirmatory clinical trials.
In a note sent to investors, Leerink Partners analyst Andrew Berens said the expansion of Enhertu’s approval may help pave the way for broader labels for other ADCs addressing other widely expressed targets, such as TROP2 and Nectin-4. TROP2 is the target of the Gilead Sciences ADC Trodelvy, which has approvals in breast and bladder cancers. Nectin-4 is targeted by Padcev, an Astellas Pharma and Pfizer ADC with approvals in bladder cancers.
“Furthermore, we think the implications of this decision will also echo across the HER2-positive solid tumor space as a whole, potentially increasing HER2 testing and treatment rates in tumors where HER2 expression is less common, such as melanoma, hepatocellular carcinoma, and head and neck cancers,” Berens said.
Photo: Getty Images, Sarah Silbiger