FDA Guidance: Start with Kids in Atopic Dermatitis Trials

October 8, 2018

Sponsors of atopic dermatitis drugs for children don’t have to wait to test a drug’s safety or efficacy on adults before beginning pediatric trials, the FDA says.

The new guidance, released last week, reverses longstanding FDA recommendations that drugs trying to treat a disease by affecting the entire body start with adult trials.

Atopic dermatitis is the dry, itchy rash caused by eczema that affects nearly 18 million Americans, most of them children. It often clusters with asthma and hay fever.

The agency says its U-turn was prompted by recommendations from a 2015 meeting of its Dermatologic and Ophthalmic Drug Advisory Committee.

The FDA acknowledges that “some major safety questions” may be left open before trials can begin.

But it says it’s “not generally necessary to have an extensive safety database in adults before initiating pediatric studies” as long as the disease isn’t potentially fatal to pediatric populations and there’s a risk doctors may be prescribing therapies off-label before trials wrap up.

Trials will have to consider a drug’s effect on children of all ages, including toddlers and infants, the guidance adds.

Sponsors may have to start with older children first if specific data from an older subpopulation can help inform the study, if there’s an “age-related technical issue” or if there is some reason to worry about a drug’s safety in younger children.

Read the final guidance here:

Re-Trials for Pediatrics Pay Off
The FDA’s pediatric exclusivity rules allowed drugmakers to reap a 680 percent return on their investments, a new analysis finds.

The Best Pharmaceuticals for Children Act of 2002 offered drugmakers six months of market exclusivity in return for running drugs already approved for adults through clinical trials again to test their safety and efficacy for children.

Congress passed the measure because it was concerned that doctors were pre­scribing adult meds to kids off-label and the pharmaceutical industry argued that limited exclusivity provided proper incentive to invest in fresh trials.

The incentive has proved lucratice, according to the analysis published in JAMA Internal Medicine.

Study author Michael S. Sinha and his colleagues at Boston’s Brigham and Women’s Hospital examined 54 drugs given exclusivity between 2007 and 2012.

They estimate pharma companies spent an average of $36.4 million to re-test their drugs in clinical trials and the median net return was $176 million—a ratio of about 680 percent.

“Meaningful knowledge of pediatric uses of pharmaceuticals has come from the pediatric exclusivity program, but at a high cost” in hefty drug prices passed along to consumers, Sinha said, noting that “other approaches … such as direct funding” for pediatric trials “may be more economically efficient.”

Advanced Cancer Trials Set
The FDA has greenlighted clinical trials for a Chinese biotech hoping to treat non-Hodgkin’s lymphoma, ovarian cancer and other advanced cancers.

Innovent Biologics is planning several trials on IBI-188, an anti-CD47 monoclonal antibody, which works by boosting patients’ immune systems and setting up markers on cancer cells for targeted treatments that spare surrounding healthy tissue.

There are about 14 ongoing clinical trials on these types of meds. But Innovent is the first Chinese company given the nod to test such a treatment.

In January, the FDA gave Innovent the go-ahead for clinical trials of Sintilimab, an anti-PD-1 antibody that also targets cancer.

Personalized Pain Trial Scores Big on Patient Satisfaction Scale
Patients gave thumbs up to a clinical trial that provided a menu of a la carte treatment options even though it didn’t make a dramatic difference in managing their pain.

In what’s believe to be the largest trial of its kind, a team at the University of California, Davis, enrolled 215 people in a single-patient multi-crossover trial to test pain management.

Often called n-of-1 trials, the single-patient, multi-crossover approach allows participants to switch between two or more therapies during the trial and allows researchers to gauge the effect of treatments on each individual.

Researchers randomly assigned 108 of the pain patients to personalized mini-trials in which they were given eight different treatment options, ranging from opioids to acupuncture, to try for between four to 12 weeks.

Participants were also given access to an open-source mobile app called Trialist, which sent reminders about beginning each treatment, daily questionnaires rating their pain, and warnings about possible side effects of their selected treatments.

The remaining 107 volunteers continued using their same pre-trial treatment.

Researchers measured patients’ pain management as well as their level of satisfaction with their treatment.

Patients in the n-of-1 trials group reported slight but statistically insignificant improvement in pain symptoms but still raved about their experience. For instance, 88 percent said Trialist was “extremely or very helpful” in keeping track of their pain.

The team reported its findings in JAMA Internal Medicine, which carried a separate editorial praising the trial for its “ambition.”

ACRES: Accreditation of Trial Sites
A nonprofit group has begun evaluating standards for first-of-its kind voluntary accreditation of clinical research sites as part of a new effort to enhance quality and speed development of new medical products worldwide.

The Alliance for Clinical Research Excellence and Safety (ACRES) is currently performing its first evaluation at research facilities owned by ActivMed, a company in Massachusetts that’s completed 720 clinical trials since it was founded in 1994.

ACRES officials believe accrediting site performance and research quality can “dramatically” shrink both the costs and time spent on clinical trials.

As part of its effort, the company is working on technology dubbed “Dynamic Accreditation” to provide real-time feedback to sites, sponsors, CROs, regulators and patients about site performance.

“The idea of site accreditation is an important one. We are sure that both our site and ACRES will learn more as we move through the beta-testing of the standards,” said Terry Stubbs, ActivMed president and CEO.

Once the pilot program wraps up, ACRES will commission an independent study to assess its impact.