The FDA defines a surrogate endpoint as “a laboratory measure or a physical sign that is intended to be used as a substitute for a clinically meaningful endpoint.” For some cancer therapies that means the recurrence of disease or other meaningful markers must be met when a definitive clinical endpoint, such as overall survival time, takes too long to achieve, according to CRO Aptiv Solutions.
Surrogate endpoints, which include biomarkers that substitute for a clinical endpoint, also may be eligible for a Breakthrough Therapy Designation from the FDA.
“The issue of surrogate endpoints, in oncology and other clinical indications, is a current topic of much discussion,” Gene Resnik, chief medical officer of Aptiv, told Outsourcing-Pharma.com. And it can get even trickier when, for example, the study of a blood tumour marker yields “an early signal of drug activity in a particular disease state even if such signal is not by itself an endpoint on which a regulator might approve the agent,” he said.
But others in the CRO industry disagree that a surrogate endpoint can speed a drug to market as there aren’t any examples of such cases, and as ultimately patient survival in an oncology trial is what really matters.
Barb Geiger, EVP of CRO Clinipace, told Outsourcing-Pharma.com, “There’s really not that many truly defined surrogate endpoints in oncology. So much of it depends on the compound, client and phase…but it’s a conversation we’re having when writing protocols.”
Dr. Lee Schacter, oncology director of Clinipace, agreed, telling us that surrogate endpoints could help to guide a compound in an early phase and help with dosing, but “as an oncologist, I can’t imagine what surrogate endpoint I would be comfortable with using. We don’t treat numbers, we treat patients. I need to be able to look at the patient and see that the survival is improved.”
Still, “trials in hematologic malignancy are using blood protein markers as surrogates for response to treatment or recurrence; the blood markers may appear before other detectable clinical or biological markers of disease,” Resnick said.
And when a surrogate endpoint is validated and established as a reliable indicator of a significant clinical endpoint, such as improved survival, regulators and sponsors may “consider use of one of the expedited processes for drug approval, such as accelerated approval or breakthrough designation,” thus saving the company time and money, he added.
“Since the desired clinical outcome can take a long time to achieve, the use of established surrogates allow FDA to approve these treatments earlier than otherwise possible,” Resnick said.
But Shacter seems to disagree, noting that in order to obtain approval from either the US FDA or EMA “in oncology you need to show overall survival and progression free survival” to inevitably bring a drug to market.
Resnick also acknowledges that many cancer treatments “are under study for conditions where the clinical outcome is, unfortunately, relatively quick. The need for a surrogate endpoint, or an expedited approval process, may not be necessary in such a clinical condition.”