ADCs are hitting a wall with their toxicity ADC, called "guided missiles equipped with chemo", by the industry, is having a hard time. See below.
Remember that Pfizer recently paid 43B$ to buy SEAGEN's ADC portfolio and Immunomedics was bought 21B$ for its ADC one.
https://www.fiercebiotech.com/biotech/astrazeneca-stock-slides-pivotal-lung-cancer-readout-daiichi-partnered-adc-spooks-investors
AstraZeneca stock slides as pivotal lung cancer readout on Daiichi-partnered ADC spooks investors
AstraZeneca and Daiichi Sankyo’s attempt to repeat the success of Enhertu has delivered its first phase 3 data. The antibody-drug conjugate (ADC) improved progression-free survival (PFS) in lung cancer patients but, with the partners yet to share numbers and “some” patients suffering fatal adverse events, shares in AstraZeneca fell almost 6% in early trading in London.
In 2020, AstraZeneca followed up its big ticket Enhertu deal by paying Daiichi $1 billion upfront for the next ADC off its production line, namely its TROP2-directed datopotamab deruxtecan (Dato-DXd). Gilead made the early running in TROP2, having paid $21 billion to buy Immunomedics for Trodelvy, but Daiichi and AstraZeneca have a shot at being first to market in non-small cell lung cancer (NSCLC).
AstraZeneca and Daiichi shared the first phase 3 results on Dato-DXd on Monday. In patients with locally advanced or metastatic NSCLC treated with at least one prior therapy, Dato-DXd significantly improved progression-free survival compared to the standard chemotherapy docetaxel. PFS is one of the primary endpoints.
On the other primary endpoint, overall survival, the researchers saw “an early trend” in favor of Dato-DXd, but, at the interim analysis, the difference between the two cohorts fell short of the prespecified threshold for statistical significance.
The wait-and-see overall survival result won't have come as a surprise to the Big Pharma. Leora Horn, global clinical head, lung cancer and lung cancer strategy at AstraZeneca, told attendees at the company’s American Society of Clinical Oncology investor event last month that “the OS data will not be mature.” AstraZeneca and Daiichi are continuing the study to gather mature data for this endpoint.
On the safety front, the partners said the Dato-DXd profile was consistent with earlier trials and no new signals were seen. Lung scarring, a key safety concern, was consistent with earlier results and most cases were low grade. In an early-phase trial, the adverse event, interstitial lung disease, was grade 3 at worst. “Some” phase 3 patients had fatal adverse events, but the partners are yet to share numbers or details.
Faced with a limited look at the results, investors feared for the worst, sending shares in AstraZeneca down 5.8% to around 106 pounds sterling ($134) by 11:20 a.m. London time on Monday morning. The partners took a more positive view of the data, outlining plans to share the results with regulatory authorities to discuss the next steps.
AstraZeneca sees Dato-DXd as a potential replacement for chemotherapy in NSCLC, leading it to pit the ADC against docetaxel in the second-line study and kick off first-line trials in combination with Merck & Co.’s Keytruda. Gilead Sciences, which already markets Trodelvy in breast cancer, is testing its rival TROP2 drug in NSCLC, and Merck and Kelun-Biotech are collaborating on another ADC against the target.