AstraZeneca-partnered Enhertu has become a bright spot in Daiichi Sankyo’s business, and the Japanese pharma has again increased its sales projection for the HER2-directed antibody-drug conjugate.
But this time, the rosier outlook reflects developments outside the U.S.
Daiichi now expects Enhertu sales to come in at 383.9 billion Japanese yen (about $2.6 billion) for the 12 months ending March 31. The number includes profits from regions where AstraZeneca books Enhertu sales.
Daiichi had already once dialed up its Enhertu forecast for its current fiscal year. The drugmaker’s projection was originally 320 billion yen back in April 2023, then Daiichi raised it to 381.7 billion yen in October.
Despite rolling out the higher global forecast, Daichii actually reduced Enhertu’s 12-month sales estimate in the U.S. by $30 million to $1.58 billion. For the first nine months of the company’s fiscal year, Enhertu generated $1.14 billion in the U.S., an increase of 55% year over year.
Across its approved indications, including second-line HER2-positive breast cancer and post-chemotherapy HER2-low breast cancer, Enhertu leads the pack in new patient share in the U.S., according to a Daiichi presentation (PDF) Wednesday.
Overall, for the three months that ended in December, Daiichi’s revenue reached 446.9 billion yen, compared with 375.5 billion yen in the quarter before it.
For the full fiscal year, Daiichi boosted its revenue forecast by 30 billion yen to 1,580 billion yen, partly thanks to a depreciating yen.
On the R&D front, Daiichi and partner AZ are expecting by September a phase 3 readout from the DESTINY-Breast06 trial. If successful, the result could move Enhertu into chemo-naïve HER2-low, HR-positive breast cancer.
The partners are also pushing for Enhertu to be used in previously treated patients with HER2-positive solid tumors, regardless of their location. Their HER2 tumor-agnostic application has been put under an FDA priority review with a target decision date of May 30, according to Daiichi. If approved, Enhertu would be the first ADC with a tumor-agnostic indication.
Besides their wide-ranging efforts on Enhertu, the two companies are busy making a case for the other ADC in their partnership, the TROP2-targeted prospect called datopotamab deruxtecan. Also known as Dato-DXd, the drug is poised to be a direct competitor to Gilead Sciences’ Trodelvy.
Daiichi expects the FDA will accept Dato-DXd’s applications for previously treated non-small cell lung cancer (NSCLC) and in pretreated HER2-low or HER2-negative, HR-positive breast cancer by March.
If approved, Dato-DXd’s lung cancer indication would likely be limited. In the TROPION-Lung01 trial, the drug only showed a disease-progression benefit in patients with non-squamous tumors, not in those with the squamous histology.
As for overall survival, Dato-Dxd cut the risk of death by 23% against the chemotherapy docetaxel in the non-squamous subgroup, although the improvement didn’t bear statistical significance.
By comparison, Gilead last week announced that Trodelvy had failed to significantly beat docetaxel at extending patients’ lives in previously treated NSCLC in the EVOKE-1 trial.
Even without an approval, Daiichi and AZ are testing Dato-DXd in more treatment settings. In November, the pair started two phase 3 trials coded TROPION-Breast04 and TROPION-Breast05. The first trial combines the ADC with AZ’s PD-L1 inhibitor Imfinzi for use before and after surgery in patients with triple-negative or HR-low, HER2-low/negative breast cancer. And the second study will evaluate Dato-DXd either by itself or in combination with Imfinzi as first-line treatment for triple-negative breast cancer.