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FDA: Generic Skin Patch Trials

October 15, 2018

Generic drug developers that use patches, inhalers, eye drops or similar means to deliver meds should hold clinical trials to test for potential side effects of skin irritation and, in the case of patches, adhesion quality, the FDA says.

The agency says it’s worried that skin patches may lose potency if jarred and loosened by everyday movements or conditions (such as moisture).

So in new draft guidance, released last week, it recommends generic drug developers hold separate clinical trials to make sure patches continue to stick and provide promised doses for the duration of treatment.

The guidance urges them to hold single-dose, randomized, two-treatment, two-period crossover trials with participants most likely to use patches to show they can withstand ordinary pressures. The draft, set to replace 2016 adhesion guidance, says single-period two-treatment-per-subject designs may also work if developers can justify why they’re a better option.

Developers should test adhesion several times, and at regular intervals, and use a four-point scale, ranging from 0 (90 percent adhesion or better) to 4 (the patch completely peels off), the agency says.

In another new draft guidance, the FDA further advises developers to measure generics’ potential side effects — most notably skin and/or eye irritation depending on the delivery system employed — against those of their brand name competitors.

It recommends testing them in clinical trials involving a “relatively small population” (i.e. hundreds of patients) and conducted under “relatively provocative conditions” during which researchers repeatedly take off and put back skin patches to see if they retain their holding power.

The best bet, says the FDA: a two-phase trial — the first, a 21-day induction phase during which patches are worn, removed and replaced for the recommended course of treatment.

That phase should be followed by a 14-to-17-day rest period and, then, a “challenge phase” during which patches are put on a new part of the body for 48 hours and the skin is tested for reactions after 30 minutes, 24 hours, 48 hours and, again, 72 hours after the patch’s removal.

Developers are urged to use a seven-point rating scale for skin irritation — from 0 (clear skin) to 7 (“Strong reaction spreading beyond the application site”).

Read the adhesion draft guidance here: www.fdanews.com/10-09-18-ANDAs.pdf.

Read the irritation draft here: www.fdanews.com/10-09-18-ANDAs2.pdf.

China OKs Rabies Vaccine Trials
A Chinese drug company says national regulators have approved pivotal clinical trials for a new rabies vaccine.

YiSheng BioPharma believes its vaccine, called PIKA, can become a “best in class” immunization against this contagious and fatal virus that causes tens of thousands of deaths annually, according to the World Health Organization.

The company plans to begin recruiting participants for its Phase III trials, set to start early next year. The vaccine won orphan status from the FDA in 2016 and has already successfully finished Phase I and Phase II studies in Singapore.

Celgene Claims Win in MS Trial
Celgene Corp.’s experimental multiple sclerosis drug helped stave off symptoms better than its rival in clinical trials.

The New Jersey-based pharma announced last week that ozanimod topped Biogen’s Avonex (interferon beta-1a or IFN) in a pair of Phase III trials. In the first trial, called SUNBEAM, researchers randomly gave two different oral doses of ozanimod or IFN to 1,346 relapsing MS patients over a year and then tested their cognitive function, which typically declines as the disease progresses. The ozanimod patients, on average, scored significantly higher than the IFN patients.

The second trial, dubbed RADIANCE, compared the annualized relapse rates for 1,392 patients in the early stages of MS and another 1,267 patients with more advanced cases of the neurological disease who took either ozanimod or IFN. Both sets of patients who took ozanimod suffered fewer relapses or exacerbations than those who took IFN, Celgene says.

MS affects an estimated one million adults in the U.S. and 2.3 million globally; women are up to three times more likely to develop the disease.

There are several types of the condition; left untreated, those who suffer from relapsing MS will develop the more serious secondary progressive form.

Celgene says it plans to apply for FDA approval to market ozanimod.

Sickle Cell Trial, Positive Results
An experimental treatment helped prevent a painful, potentially fatal complication in a clinical trial of patients with sickle cell disease.

Novartis tested crizanluzumab in 132 patients in a Phase II clinical trial over three years to see if it could prevent vaso-occlusive crisis. More than half of the patients received crizanluzumab and the rest were given a placebo.

Researchers continued to monitor them for a year after the trial ended: nearly 36 percent of those in the crizanlizumab group did not suffer a single vaso-occlusive crisis, compared to about 17 percent in the placebo group.

Novartis is currently recruiting patients for a Phase III trial on the drug.