Fast-tracked cancer drugs: Balancing accelerated approvals with evidence gaps and policy challenges

What factors influence the transition of new cancer medicines from an accelerated regulatory pathway to full approval, and what are the policy implications?

A new report has revealed that for the accelerated approvals granted by the US Food and Drug Administration (FDA) to 113 cancer drugs between 1992 to 2022, 61% progressed to full approval while 18% were withdrawn. The rest remain in the accelerated approval pathway.

FDA’s accelerated approval pathway that expedites drug approval for life-threatening conditions is based on data from early clinical trials and unvalidated surrogate measures, with pending confirmatory clinical trials to transition to full approval.

The Therapeutic Goods Administration (TGA) similarly offers a provisional approval pathway which involves a 2-year initial period, with the possibility of two extensions, each up to 2 years, for a total of 6 years, during which confirmatory data must be submitted for transition to full TGA registration.

Yet, delays in completing confirmatory clinical trials have raised concerns about exposing patients to clinical risks, particularly when the trials yield negative results leading to drug withdrawals.

According to the new report, faster conversion to full approval was linked to priority review designation, with a median conversion time of 2.90 years compared to 5.11 years under regular review (p = .002). Cancer medicines undergoing confirmatory trials during accelerated approval completed studies in a shorter timeframe (median, 2.78 years vs 5.59 years; p < .001).

Importantly, medicines demonstrating significant clinical benefit in confirmatory trials achieved quicker conversion to full approval (median, 2.34 years) compared to those with lesser benefit (median, 3.91 years; p < .001).

“In these cases, important drugs are being made available earlier for the benefit of patients. However, for the remaining indications, the FDA must work to minimise the duration during which patients and physicians use drugs approved via accelerated pathway without robust data on their efficacy and safety,” noted the study’s authors.

Policy Implications?

While surrogate measures such as progression-free and disease-free survival currently support most accelerated approvals, questions arise about their reliability in correlating with overall survival in clinical settings.

“This raises questions about whether the pathway should continue to support treatments based on end points that lack validated surrogacy,” the authors questioned.

The authors recommend that the regulatory agency should consider restricting accelerated pathway to drugs that demonstrate meaningful activity or clinical benefit in early clinical trials, and no serious side effects.

Additionally, the regulatory agency should leverage its statutory authority to ensure confirmatory trials commence promptly post-accelerated approval, with mandated annual public reporting on trial status. Confirmatory trials should validate clinical benefits in terms of overall survival, quality of life, or substantial clinical benefits.

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