ADC Therapeutics shares fell 53% in after-hours trading after the company reported phase III data for Zynlonta that met its primary efficacy endpoint but showed a higher rate of fatal adverse events in the treatment arm. The LOTIS-5 trial achieved progression-free survival of 6.1 months versus 4.7 months for standard therapy, though 13.2% of patients in the Zynlonta arm experienced Grade 5 events versus 4.6% in the control group.
ADC Therapeutics shares plunged 53% in after-hours trading Wednesday as safety concerns from a phase III lymphoma study of Zynlonta overshadowed positive efficacy results.
"Most of the deaths in the treatment arm were among patients aged 75 and older and were due to infections," Ameet Mallik, chief executive officer of ADC Therapeutics, said on a conference call.
The phase III LOTIS-5 confirmatory study enrolled 440 patients with relapsed or refractory diffuse large B-cell lymphoma who had received at least one prior line of systemic therapy. The combination of loncastuximab tesirine (Zynlonta), a CD19-targeted antibody-drug conjugate, plus Roche's Rituxan (rituximab) achieved a median progression-free survival of 6.1 months compared with 4.7 months for the standard R-GemOx regimen. Complete response rates reached 39.5% versus 26.7%, and median duration of complete response extended to 16.8 months from 12.3 months. Nearly half of patients achieving complete remission in the Zynlonta arm remained in remission at 24 months compared with 16.7% in the control group.
However, serious adverse events occurred in 49% of patients receiving the Zynlonta combination versus 34.5% in the control arm. Treatment discontinuations due to adverse events reached 25.5% compared with 9.1%. Grade 5 treatment-emergent adverse events — generally fatal — totaled 27 cases, or 13.2%, in the experimental arm versus nine cases, or 4.6%, in the control group. The company noted that most Grade 5 events in the Zynlonta arm occurred in patients aged 75 years or older.
The safety imbalance threatens ADC Therapeutics' effort to convert Zynlonta's accelerated approval to full approval and expand its label from third-line to second-line use. Zynlonta generated $74 million in sales last year and $20 million in the first quarter of 2026. ADC Therapeutics reported $231 million in cash with a runway extending into 2028.
The company plans a pre-supplemental biologics license application meeting with the FDA in August and targets a regulatory submission in the fourth quarter of 2026. ADC Therapeutics said it will also evaluate cost-reduction measures alongside its regulatory strategy.
The 53% after-hours decline signals that investors view the safety profile as a material risk to Zynlonta's commercial prospects, even if the FDA ultimately approves the regimen. The pre-sBLA meeting with the FDA in August will be the next key catalyst for the stock.
This article is for informational purposes only and does not constitute investment advice.
