Among AstraZeneca’s growth drivers with $5 billion or more in peak sales potential, the company is counting on Daiichi Sankyo-partnered Enhertu to chart new territory. And stalling sales underscore the challenges facing the HER2 drug.
Combined Enhertu sales for AZ and Daiichi reached $893 million in the second quarter, reflecting a mere 1.6% sequential increase from the first three months of 2024. And the lackluster performance came despite the antibody-drug conjugate’s tumor-agnostic approval in the U.S. in April to treat HER2-positive solid tumors regardless of their locations.
Nevertheless, AZ’s oncology business chief Dave Fredrickson said the company still anticipates Enhertu’s return to “more robust sequential growth” in the second half of the year.
Enhertu ranks among six in-market products that AZ expects could reach more than $5 billion global sales at peak. Besides its key role in AZ’s and Daiichi’s businesses, the HER2 drug also serves as an industrywide barometer for the promise of ADCs.
AZ attributed Enhertu’s slowdown partly to a destocking dynamic in China after an inventory buildup in the first quarter for the drug’s ongoing launch in breast cancer. In the U.S., Fredrickson noted “sequential demand growth” and “early launch signals” following the tumor-agnostic approval, including updated treatment guidelines and a rapid increase in physician awareness.
During an investor call Thursday, Fredrickson said AZ expects Enhertu to grow in China, Europe and the U.S. later this year. But, to achieve that, Enhertu needs to navigate “harder yards” and further into what Fredrickson called the “clear standard-of-care zone” within its pioneering HER2-low breast cancer indication.
In American football, when the game gets into tight spaces and the players struggle to move one another, those are considered “harder yards.”
After an FDA approval in August 2022, Enhertu has secured around 55% to 60% market share in HER2-low disease, Fredrickson said. That was slightly better than the roughly 50% patient share held by the medicine at the beginning of the year, when concerns over a potential Enhertu plateau first came to the fore.
“I think that we need to continue to work on changing some of the inertia and embedded behaviors that have existed in the past to get to the share gains that we have,” Fredrickson said.
The partners are now trying to move Enhertu into breast cancer with even lower expression of HER2 thanks to positive findings from the DESTINY-Breast06 trial. But even before a potential FDA go-ahead, Fredrickson expects the National Comprehensive Cancer Network will include Enhertu’s HER2-ultralow use in its treatment guidance, which could help boost sales.
Looking further ahead, AZ expects Enhertu readouts in 2025 from DESTINY-Breast09 in first-line HER2-positive breast cancer and DESTINY-Breast11 in patients with high-risk, HER2-positive early-stage breast cancer in the presurgical neoadjuvant setting.
Beyond Enhertu, AZ and Daiichi are awaiting an FDA decision on their second ADC, the TROP2-directed datopotamab deruxtecan (Dato-DXd) in nonsquamous non-small cell lung cancer (NSCLC). That application faces some uncertainties as its underlying TROPION-Lung01 trial failed to reach statistical significance on overall survival in a broader population that also includes patients with squamous tumors.
During Thursday’s conference call, AZ’s oncology R&D head Susan Galbraith, Ph.D., offered no updates on the application’s progress with the FDA. In response to a question about whether AZ expects an advisory committee meeting, Galbraith said the communication about such meetings can happen at any point during the FDA review period.
Dato-DXd is among 12 pipeline programs that carry peak sales potential of $5 billion or more, according to AZ.
Meanwhile, AZ is defending itself at an FDA advisory committee meeting Thursday for Imfinzi’s use both before and after surgery in early-stage NSCLC. The FDA has raised concerns that such perioperative trial designs do not isolate the contribution of each treatment phase, including whether continuous dosing of patients is necessary even if they have shown no signs of cancer in tissue samples removed during surgery.
Imfinzi and its CTLA-4 partner Imjudo together brought in $1.22 billion sales in the second quarter, falling 5% below industry watchers’ expectations, according to Leerink Partners.
Overall, AZ’s total revenues of $12.9 billion beat consensus estimates by 3%, with strong performances coming from the newly launched breast cancer drug Truqap (54% above consensus) and the old respiratory disease med Symbicort (28% above).
As a result, AZ raised its full-year guidance and now projects total revenue and core earnings per share to grow by a mid-teens percentage at constant exchange rates versus a low double-digit to low-teens percentage previously.