China’s drug regulators released a draft guideline on cancer therapy development last week. Stock prices of several leading oncology drugmakers and CROs took a beating as investors feared the new rule would have a chilling effect on R&D.
But as two industry experts view it, the guideline’s call for a patient-oriented approach to cancer drug R&D—including its proposed requirement for using standard-of-care treatments in clinical trials—is all but formalizing existing practice.
The market—and the industry—might be overreacting to the announcement and probably misinterpreted the drug authority’s intention, Jianqing Chang, vice president of drug regulatory policy at Chinese CRO giant Tigermed, said in an interview. There isn’t too much to be concerned about, Justin Wang, head of L.E.K. Consulting’s China practice, echoed in a separate email interview.
Both experts believe the rule will accelerate cancer drug development in China by directing resources to true innovation. Industry front-runners need not fear; it’s drugmakers that are just piling into the same old targets that should think twice before knocking on the regulator’s door, they suggested.
Friday, the Center for Drug Evaluation at China’s National Medical Products Administration released (Chinese) a draft guidance for conducting oncology drug trials. It stressed that all cancer drug R&D efforts should focus on creating “clinical value,” namely, meeting patients’ needs.
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From the 28-page document, the biopharma industry—and media outlets at home and abroad—picked up one particular requirement, which appeared to have caused the panic. It states that late-stage trials should use best standard of care as a control, rather than compare drug candidates to treatments that have already been replaced in clinical practice. Placebo and best supportive care should only be considered when no standard exists, and the latter is preferred whenever available.
The item effectively raises the regulatory bar for oncology drugs, several market watchers suggested. It would be more costly to run oncology drug trials under the new guidelines and more difficult to win approval, they figured.
Is it new?
As Chang pointed out, the Chinese government first put forward the “clinical value” concept in a policy opinion in 2015, which marked the beginning of the country’s ongoing drug regulatory reform. The goal is to encourage drugmakers to solve real clinical problems—to offer patients drugs that work better, are safer or are more convenient instead of “conducting R&D for R&D’s sake,” she said.
Now, the CDE is only summarizing nearly six years of exploration and experience in writing rather than inviting a “sudden transformation,” Chang added. “Little has been really changed fundamentally, and the CDE is already [following the rules] in practice,” she said. “The guideline is trying to provide a roadmap that cancer drug R&D should be done in an orderly manner and offer patients clinical value.”
As for the control arm requirement, most leading pharmas and biotechs are already using standard of care as the comparator in their trials, Wang noted, so “it seems CDE aims to formalize this requirement.”
Using an outdated regimen when there’s a clear standard of care wouldn’t even pass muster with a trial’s ethics committee, Chang noted. And even without a formal rule, the CDE is carefully reviewing applications to safeguard quality, Wang said. Because standards of care are evolving, the rule is to ensure that trial designs closely follow practice development as well, he added.
What’s the standard?
Many industry watchers believe that the guidelines are aimed at increasingly crowded fields in oncology, such as PD-1/L1 and CAR-T. China’s drug regulators have already approved eight PD-1/L1 inhibitors for various indications, with about a dozen more in clinical development.
In fact, the CDE had previously made the control arm requirement clear, at least for PD-1/L1s. During a presentation summarizing the agency’s oncology drug review work in 2020 at last year’s Chinese Society of Clinical Oncology annual meeting in September, Zhimin Yang, an official with the Chinese CDE, said when designing a PD-1 trial, the control arm must use the commonly recognized standard care. She raised the example of first-line lung cancer, noting that the standard might have shifted from chemotherapy to immuno-oncology treatments.
Chang believes the CDE’s guideline doesn’t mean drug reviewers would necessarily immediately adopt any newly approved drug as the new standard for clinical research. Establishing a gold-standard treatment requires real-world clinical experience and evidence, and that takes time, she said.
While the CDE didn’t specify how it determines “best standard of care,” Chang said the agency will likely want companies to make “scientific, reasonable and ethical” decisions.
Encouraging true innovation over me-too drugs
While the guidelines don’t mean a change of course at the CDE, they likely will discourage some companies from pushing ahead with drugs that may not live up to existing standard treatments.
The intention is to further improve the quality of oncology drug development, and “to lift China out of the fierce me-too competition,” Wang said.
This seems to be a strong signal to the domestic pharma and biotech industries that they should focus on true innovation (i.e., at least me-betters) and avoid crowding into me-too drugs, he said. “This is to foster healthier development of the industry, and ultimately domestic innovative pharmas and patients will benefit.”