The FDA says sponsors considering adaptive studies for early phase cancer treatments should focus on patients with no other options. The agency notes that so-called expansion cohort trials — which start out relatively small but expand if a potential treatment shows promise — can be a way to get a treatment to market more quickly. The thinking is, the more participants in earlier trials the more likely it is to find and fix (if possible) glitches — ensuring faster approval or scrapping the potential treatment in its infancy if it doesn’t work or if risks outweigh benefits. “A lot of time and cost of clinical development is spent waiting in between the start and end of the phases of trials,” FDA Commissioner Scott Gottlieb said in a statement. “Expansion cohort trials can bring efficiency to drug development, potentially reducing development costs and time.” In a 17-page draft guidance released last week, the FDA says it wants to “establish an infrastructure” designed to help sponsors use cohorts to speed drug approvals without compromising safety. Its top recommendation: Focus on patients who are most seriously ill and don’t have any other treatment options. The agency also encourages researchers to hire centralized data management committees and IRBs and have them meet regularly to discuss latest findings and best next steps. “It is critical that investigators, IRBs and regulators are updated with new safety information so that they can provide the necessary oversight for the protection of human subjects and so that investigators can ensure that patients can provide adequate informed consent,” the draft document says. The jury’s still out on the effect of expansion cohorts. A 2017 study by Texas researchers, published in the Journal of the American Association for Cancer Research, analyzed 533 Phase I cancer trials between 2006 and 2011. They found the ones that used expansion cohorts went on to have successful Phase II trials at nearly twice the rate (48 percent) as studies that didn’t (27 percent). But just a year earlier, a team of Cleveland researchers analyzed 252 cancer trials conducted between 2004 and 2014 and found expansion cohorts made little or no statistical difference between success or failure in Phase II trials. Read the FDA’s draft guidance here: www.fdanews.com/08-10-18-DraftGuidance.pdf.
The FDA has proposed allowing adolescents to join adult oncology clinical trials as long as their disease or the drug target is the same. Under proposed guidelines, teens would make the cut if the agency approves the pharmacokinetic and toxicity data for adults and sponsors adjust dosing for patients’ body size. Drug giant PhRMA in comments urged the FDA to work with global regulatory agencies “to promote adoption of similar pragmatic approaches.” PhRMA also encouraged the agency to discuss its recommendations with institutional review boards to ensure they’re aware of them. “In order to fully realize the benefits of adolescent participation in adult trials, input from the IRB community and acceptance of the draft guidance will be necessary,” the industry group wrote. GlaxoSmithKline, meanwhile, suggested the FDA clarify a provision on teens in early phase trials to limit enrollment to cases with a “strong similarity in disease between adolescents and adults.” It also urged the agency to require sponsors to “consult with the responsible FDA review division to determine the amount and type of adult data needed before enrolling adolescent patients.”
The FDA last week approved a new drug for two rare forms of non-Hodgkin lymphoma. Regulators say that adults with either mycosis fungoides or Sezary syndrome can try Poteligeo as an IV treatment as long as they’ve already tried chemo or at least one other systemic treatment. Both diseases turn white blood cells malignant and attack the skin. Poteligeo, the brand name for mogamulizumab-kpkc, is a monoclonal antibody that binds to a protein on some cancer cells. It’s the first treatment ever approved for Sezary syndrome, the most virulent of the two diseases. The approval comes after a nearly five-year, Phase III clinical trial with 372 patients showed those who took Poteligeo, on average, lived longer without seeing their cancers grow compared to a chemotherapy treatment. The median progression-free survival was 7.6 months for Poteligeo patients compared to a median of 3.1 months for patients on chemo, the FDA said.
The FDA has signed off on two malaria treatments, one designed to help prevent relapse of the disease, the other a preventive measure. The agency approved GlaxoSmithKline’s Krintafel after clinical trials of 522 malaria patients in eight sites in Asia, Africa and Latin America showed that taking Krintafel along with anti-malarial drug chloroquine for three days kept patients malaria-free for up to six months. The FDA last week also greenlighted 60 Degrees Pharmaceuticals’ Arakoda tablets. It’s the first preventive malaria medicine to win federal approval in two decades. 60 Degrees said it worked with the U.S. Army to test Arakoda, the brand name for tafenoquine, in 21 clinical trials involving 3,100 subjects. Both companies will have to conduct post-marketing studies to make sure that their drugs are safe and effective for children, elders and the obese.