The Ballad of TIGIT

Roche’s TIGIT drug tiragolumab failed to meet primary endpoints in Phase 3 trials for non-small-cell lung cancer, marking a significant setback for the once-promising immunotherapy class.

TIGIT drugs, including Roche’s tiragolumab, were highly anticipated after early-phase trials showed promising response rates. Roche’s initial Phase 2 trial in 2020 reported a response rate of 31% versus 16% with placebo, leading to FDA breakthrough designation in January 2021. Multiple companies, including Merck, BMS, BeiGene, Arcus, and GSK, invested heavily in developing their own anti-TIGIT agents, running numerous parallel trials. Roche’s ‘SKYSCRAPER’ program, involving around 5,000 patients across twelve trials, represented one of the largest efforts in immuno-oncology targeting TIGIT. However, recent results, including Roche’s Phase 3 trial announced in May 2022, have failed to demonstrate the expected efficacy, leading to questions about the future of TIGIT as a viable target in cancer therapy.

Why It Matters

The failure of TIGIT drugs in late-stage trials signifies a major setback for a drug class once considered the next frontier in cancer immunotherapy. It dampens investor enthusiasm and prompts a reassessment of immune checkpoint targets, potentially shifting focus away from TIGIT in future research and development. This development underscores the unpredictable nature of drug discovery, especially in complex fields like immuno-oncology, and may influence strategic decisions across the industry.

Background

TIGIT emerged from research into immune regulation, with Roche’s 2014 publication highlighting its role in antitumor activity. The initial promise was fueled by early trial results and the success of other checkpoint inhibitors like Keytruda, which revolutionized cancer treatment. The industry’s intense investment in TIGIT drugs reflected high expectations, with Roche’s ‘SKYSCRAPER’ program representing one of the largest parallel-indication efforts. Despite early optimism, subsequent Phase 3 trials have not met primary endpoints, casting doubt on the class’s future viability.

“The latest trial results do not meet our expectations and we are carefully evaluating next steps.”

— Roche spokesperson

“The TIGIT class has faced a significant setback. It’s a reminder of how challenging immunotherapy development can be, even with promising early data.”

— Industry analyst

What Remains Unclear

It remains unclear whether other TIGIT drugs will succeed or if the entire class will be abandoned. Some companies may pivot to different targets or combination strategies, but the recent failures cast doubt on TIGIT’s future prospects.

What’s Next

Companies involved in TIGIT development are likely to reassess their pipelines, possibly shifting focus to alternative immunotherapy targets or combination approaches. Further trial results and analyses are expected over the next year to determine whether any TIGIT agents can recover from these setbacks.

Key Questions

Why did TIGIT drugs fail in late-stage trials?

While early results were promising, later-phase trials did not demonstrate sufficient efficacy in treating cancers, possibly due to complex immune interactions or insufficient patient response.

Does this mean all TIGIT drugs are dead?

Not necessarily. While recent failures cast doubt on the class’s viability, some companies may continue research or explore combination therapies. However, the outlook is uncertain.

What impact will this have on cancer immunotherapy research?

This setback may lead to a shift in focus toward other immune targets or strategies, and investors may become more cautious about high-risk immunotherapy classes.

What was the initial promise of TIGIT drugs?

Early studies suggested that blocking TIGIT could unleash immune responses against tumors more effectively than existing therapies, fueling high industry investment.

Source: Hacker News