FDA urges sponsors to increase expanded access to experimental treatment
When deemed appropriate, patients with very serious, immediately life-threatening illnesses who are not enrolled in a clinical trial have been given FDA-supported expanded access (EA) to investigational medical treatments when nothing else is currently available to help. Since 2010, drug sponsors and manufacturers have given the opportunity of such access to more than 13,000 patients but 2009 regulations say that the use of investigational drugs requires balancing several factors. One includes the public’s wish to have some of these treatments developed and marketed for broader patient access. But that availability often isn’t an option – even for patients who completed a clinical trial and had promising results from the experimental treatment. FDA leaders, in a joint statement released late last week, have indicated they’d like that to change.
“Once a trial is complete, EA is generally available when clinical trial results show that the drug is effective in the studied population,” said FDA in its press announcement. “However, sometimes drugs that have not shown benefit across the overall study population may still be providing benefit for individual patients. In such situations, EA may have a role in allowing patients to have continued access to the drug. We would generally support such efforts. Providing EA to patients who undertook the risks that are inherent to participating in any clinical trial is an acknowledgement of the contribution these patients have made to the overall drug development program.
“Of course, in situations where an experimental treatment is potentially associated with substantial risk -- and where the therapy has not been demonstrated to be effective in a trial -- continued access must be carefully considered by the physician and the patient, and weighed by the sponsor, especially if further development of the drug is being reconsidered,” FDA continued.
However, many of these therapies are developed by smaller companies with just that one experimental product – which is often complex and expensive to manufacture – and only have enough to supply research, not EA. It’s just not fiscally feasible, in other words. In addition, FDA says “persistent misperceptions among pharmaceutical companies about the risks of providing a drug under EA, despite evidence to the contrary,” is another barrier to EA.
An FDA analysis, the agency said, of more than 10,000 EA applications from 2005 to 2014 shows that the incidence of a clinical hold due to an adverse event on an EA IND was 0.2 percent compared to 7.9 percent for clinical holds for all commercial investigational drug development programs. The two cases of clinical hold resulting from an adverse event in an EA IND occurred in response to the deaths of two cancer patients, who were receiving treatment under different EA INDs, shortly after infusion of the investigational drug. In both cases, the clinical holds were resolved. In addition, a review of more than 300 regulatory decisions between 2010 and 2016 shows that EA did not result in a negative decision on any application. In only one case did a final label include a drug interaction based on EA experience alone.
“It’s very rare that EA impacts a clinical development program in a negative way,” FDA stated. “In addition, while perhaps not commonplace, EA may add to the evidence for approval. While EA may not be feasible in every situation, concerns about regulatory risks are often overstated. Such concerns are not supported by the data.”