Two separate late-stage failures were announced today by Roche and AstraZeneca, adding fuel to the debate over regulatory standards and whether the current FDA process is excessively slow and burdensome.
On Wednesday, Basel, Switzerland-based Roche revealed its prized anti-PD-L1 monoclonal antibody Tecentriq (atezolizumab) failed to reach its primary endpoints in a Phase 3 trial.
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On the same day, AstraZeneca reported that its investigational anti-interleukin-13 (IL-13) therapy tralokinumab had fallen short in the first of two pivotal Phase 3 trials for patients with severe, uncontrolled asthma.
It follows an eye-opening study published in JAMA on Tuesday by researchers at the Yale School of Medicine. The authors determined that 71 out of the 222 drugs approved between 2000-2010 “were withdrawn, required a “black box” warning on side effects or warranted a safety announcement about new risks to the public.”
Put together, this week seems to be a win for those defending due process for drug review. But then again, it’s only Wednesday.
The issue for both Roche and AstraZeneca’s trials was efficacy, not safety. Yet in both instances, the company and its stakeholders were caught off guard because earlier data had been convincing.
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In a promising Phase 2 trial, Roche’s Tecentriq had demonstrated a strong tumor response rate and duration of response in patients with locally advanced or metastatic urothelial cancer (mUC) that had failed treatment with a platinum-based chemotherapy.
When these “surrogate” response and durability endpoints are used, the assumption is that they will translate to more months or years of life — the ultimate goal. As such, the encouraging Phase 2 data prompted the FDA to grant Tecentriq accelerated approval for mUC.
However, in an unexpected turn of events, the drug failed to hit its primary endpoint of overall survival (OS) compared to chemotherapy in the recently completed Phase 3 IMvigor211 trial. Roche said in a statement that the cause of the failure is not yet known.
“The IMvigor211 data will be further examined in an effort to better understand these results, including the initial observation that the chemotherapy arm results were better than study design assumptions.”
Tecentriq was approved in October 2016 for the treatment of patients with metastatic non-small cell lung cancer (NSCLC). Roche now has more than 30 ongoing trials evaluating the drug as a monotherapy or in combination with other drugs, underscoring the importance of Tecentriq for its long-term sales.
Cambridge, U.K.-based AstraZeneca and its global biologics research and development arm MedImmune had similarly discouraging news.
In the first of two pivotal Phase 3 trials, tralokinumab failed to reduce the annual asthma exacerbation rate (AAER) in a statistically significant way, as compared to a placebo.
As is common practice, AstraZeneca ran its two pivotal Phase 3 trials in parallel. When everything goes well, this expedites the path-to-market. On the other hand, it backfires if the first Phase 3 data are negative because it leaves no room to revise the trial design.
The company expects a data readout from the second study in the second half of 2017.
Sean Bohen, CMO and executive VP of Global Medicines Development at AstraZeneca, noted that the team may have to review its target population.
“Severe asthma is a heterogeneous disease with significant unmet needs and we will now await the STRATOS 2 results in the second half of 2017 to explore the potential to treat a sub-group of uncontrolled asthma patients with tralokinumab,” he said in a prepared statement.
Photo: pictafolio, Getty Images
