AstraZeneca, Daiichi Sankyo's Enhertu wins historic HER2 tumor-agnostic FDA nod

With Enhertu at the heart of AstraZeneca and Daiichi Sankyo’s respective goals for oncology growth, the partners have significantly expanded the antibody-drug conjugate’s (ADC's) reach in the U.S.

Late last week, the FDA granted an accelerated approval for Enhertu to treat adults with unresectable or metastatic HER2-positive solid tumors. The approval makes Enhertu the first FDA approved tumor-agnostic HER2-directed ADC and clears the drug for use in patients who’ve already received primary systemic treatment and have no other satisfactory alternatives, AZ said in a Friday release.

Because AZ and Daiichi’s latest Enhertu approval utilized the FDA’s accelerated pathway, the partners will likely have to run a confirmatory trial to verify the drug’s benefit and keep hold of their new green light. The accelerated nod is based on objective response rate (ORR) and duration of response (DoR) findings from a midstage study.

The latest nod marks Enhertu’s fifth approved indication in the U.S. The ADC, which won its original nod in 2019, is also cleared to treat HER2-positive and HER2-low breast cancer, plus gastric cancer and non-small cell lung cancer (NSCLC).

The FDA based Enhertu’s tumor-agnostic approval on results from the phase 2 trial DESTINY-PanTumor02, which looked at patients with HER2-positive tumors including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic or other tumors. In the study, patients on Enhertu experienced an overall response rate of 51% and a median duration of response of 19.4 months, according to AstraZeneca’s press release.

AZ and Daiichi also examined the effect of Enhertu on patients with confirmed HER2-positive NSCLC and centrally confirmed HER2-positive colorectal cancer in the respective DESTINY-Lung01 and DESTINY-CRC02 trials.

Enhertu’s safety across all three studies was on par with the ADC’s previously observed profile, AZ added.

Enhertu has recently become one of the key drugs in AstraZeneca and Daiichi Sankyo’s arsenal. For all of 2023, AZ recorded $1.28 billion in Enhertu revenue, which mainly included its share of profits and royalties in certain markets, including the U.S.

Combined sales of the drug across both companies hit $2.57 billion in 2023, more than doubling from the $1.25 billion haul Enhertu brought home in 2022.

While AstraZeneca and Daiichi execs have previously voiced some concern about their ADC star plateauing in the HER2-low setting, the latest pan-tumor nod could help Enhertu reach “several thousands” of patients across multiple tumor types, AZ’s oncology business chief Dave Fredrickson said on a conference call in February.

Back in January, meanwhile, Daiichi upped its sales forecast for Enhertu overall, while at the same time reducing its projection in the U.S.

At the time, Daiichi said it expected Enhertu sales to clock in at 383.9 billion Japanese yen (about $2.6 billion) for the 12 months ending March 31, including profits from regions where AZ books sales of the ADC.

Along with that boosted global forecast, Daiichi reduced its 12-month sales projection in the U.S. by $30 million to $1.58 billion.

Daiichi adjusted Enhertu’s sales forecast because it wanted to be “as accurate as possible about the numbers,” a company exec said on a call at the time.

“In terms of the future growth, we have no concern at all,” the Daiichi exec said.