Daiichi Sankyo and Merck Receive FDA Complete Response Letter for HER3-DXd Due to Third-Party Manufacturing Issues

On June 26, Daiichi Sankyo and MSD jointly announced that they had received a Complete Response Letter (CRL) from the FDA regarding the Biologics License Application (BLA) for HER3-DXd (Patritumab Deruxtecan) intended for patients with locally advanced or metastatic NSCLC harboring EGFR mutations who have received at least two prior systemic therapies, due toThird-Party Production Facility Issues。

Source: Daiichi Sankyo Official Website

In December last year, the two companies announced that the BLA application for the HER3 ADC new drug Patritumab Deruxtecan had been accepted by the FDA and granted priority review status for locally recurrent or metastatic EGFR-mutated non-small cell lung cancer patients who have previously received two or more systemic treatments.

This is the world's first HER3-targeted new drug to be submitted for marketing.It is Daiichi Sankyo's third ADC "masterpiece" following Enhertu and Dato-DXd.

This marketing application is based on the pivotal Phase II clinical trial.HERTHENA-Lung01 The research results. This study(ClinicalTrials.gov, NCT04619004) ThisPreviously announced at the 2023 WCLC,Included patients with advanced EGFR-mutated NSCLC who had previously received one EGFR-TKI treatment and platinum-based chemotherapy, and were administered two different HER3-DXd dosing regimens: 5.6 mg/kg IV Q3W or 3.2-4.8-6.4 mg/kg. The primary endpoint of the trial was the cORR assessed by BICR based on RECIST v1.1.

The results showed that, in 225 patients with EGFR-mutated locally advanced or metastatic NSCLC who progressed after EGFR-TKI and platinum-based chemotherapy,ORR was 29.8%(95% CI: 23.9-36.2), including 1 case of CR and 66 cases of PR;The median duration of response was 6.4 months.（95%CI：4.9-7.8）。

MSD and Daiichi Sankyo reached an agreement on October 19, 2023. Both partiesHER3-DXd、I-DXd And R-Dxd Three Dxd-ADC candidate drugs reach global development and commercialization agreementsTo jointly develop and commercialize these three ADCs globally, Daiichi Sankyo retains exclusive rights in Japan and is fully responsible for production and supply.

MSD pays $4.5 billion upfront, a $1 billion refundable upfront payment related to R&D costs, and up to $16.5 billion in commercial milestone payments, with the total agreement amounting to $22 billion.