Another of Mersana's ADCs slapped with FDA hold, this time over bleeding events that include 5 deaths

Mersana Therapeutics has received another FDA hold linked to a patient's death. This time it's the biotech's lead antibody-drug conjugate (ADC) that has had the clamps put down by the regulator over bleeding events in patients that have included five fatalities.

The company reported that trials of its lead asset, UpRi, had seen a higher rate of serious bleeding events in treated patients with platinum-resistant ovarian cancer than in the background population, prompting regulators to place two ongoing studies of the ADC on partial hold. Mersana has dosed about 560 patients to date, according to Thursday’s disclosure

The partial holds apply to the company’s phase 3 UP-NEXT trial and phase 1 dose expansion trial, UPGRADE-A, halting recruitment in both. Mersana’s registrational single-arm trial, UPLIFT, is unscathed after completing enrollment in October. Patients already enrolled in any of the three trials are able to continue treatment. 

News of the holds come after the ADC-focused drug developer submitted a fresh batch of safety data to regulators, which included details on the five fatal bleeding episodes. The company says an investigation is ongoing to determine their cause. 

In the meantime, Mersana says it's awaiting formal written notice from regulators on the holds and expects the FDA will ask for more comprehensive safety data. The biotech also plans to submit safety and efficacy data from the UPLIFT trial, which is slated to have topline results available in August. 

The company’s share price unsurprisingly fell through the floor shortly after the market opened, down almost 60% to $4.06 from a Wednesday closing price of $9.55. That wipes out virtually all gains made in the last seven weeks as Mersana was buoyed by the potential for the company to submit an approval application for UpRi by the end of the year. But with the safety profile now in question, investors evidently are reeling back their bets. 

Mersana’s potential has risen over the last year and a half thanks in part to a trio of partnerships with GSK, Janssen and Merck KGaA. The combined value of the three deals is north of $3 billion. However, the collaboration with GSK was thrown into doubt in March after a patient in the first trial of the two companies' partnered asset, XMT-2056, suffered a fatal serious adverse event that was deemed to be related to the therapy.

It remains to be seen how delays to recruitment in the two impacted trials of UpRi will affect Mersana’s larger clinical development plan and the capital to pay for it. The company reported having nearly $280 million on hand as of the end of March, enough to last into the second half of 2024. Mersana reported a 32% increase in R&D spending in the first quarter of 2023 compared to the first quarter of 2022, due in part to increased headcount and higher manufacturing and clinical costs.