Teva Zecuity's Safety: Burns Go From Non-Issue In Label To Product Puller

Fate of migraine patch remains uncertian after 'large number' of patients suffer burns and scars; adverse event was issue during review of transdermal sumatriptan product, but didn't even make it into labeling; nine months later the problems have forced Teva to suspend marketing.

Nine months after launching its migraine treatment Zecuity (sumatriptan iontophoretic transdermal system), Teva Pharmaceutical Industries Ltd. has voluntarily suspended marketing of the patch following patient reports of burning and scarring. The move caps a run of events in which the burns and scars went from a review concern, to a non-issue in labeling, to causing the product to be pulled from pharmacies.

Whether the product will return to market will depend on the outcome of investigations of the cause of the adverse reactions. In a June 13 release, Teva announced that it has received post-marketing reports of application site reactions described as burns and scars in patients treated with Zecuity.

The problems have appeared even though the product does not seem to have been used by very many patients. Teva has not disclosed sales of Zecuity, which indicates that revenues are modest.

Asked about the number of reports the company has received, a Teva spokesperson said the reports of burns and/or scars have been spontaneous and "the true frequency cannot be determined at this time." She said the firm is working with FDA to explain and characterize the adverse reactions and determine the feasibility of bringing Zecuity back to the market.

"If such actions can restore a favorable benefit risk profile for patients with migraine, Teva will work with the FDA to restore patient access to this therapy," the spokesperson stated.

The only approved migraine patch, the product delivers a controlled dose of sumatriptan through the skin using a battery-powered patch that is wraped around the upper arm or thigh. Oral triptans are a mainstay of migraine therapy and available generically, but Zecuity delivers a controlled dose of sumatriptan through the skin via the battery-powered patch. Its mode of delivery is viewed as being particularly beneficial to migraine sufferers with nausea.

"Given our deep commitment to patient safety, we will engage in a voluntary suspension of marketing while we continue our investigation into the root cause of these adverse skin reactions," President and CEO Rob Koremans stated in the release. The firm also issued a pharmacy-level recall of the product.

In a same-day drug safety communication about Zecuity, FDA stated that "a large number of patients" have reported burns or scars on the skin where the patch was worn. It said the reports included descriptions of severe redness, pain, skin discoloration, blistering, and cracked skin.

"As a result, FDA is investigating these serious adverse events to determine whether future regulatory action is needed, and will update the public with new information when the FDA review is complete," the notice states.

Teva advised patients to discontinue use of Zecuity and discuss alternative treatment options with their physicians.

FDA Worried About Scars; Labeling Didn't

The recall follows an initial drug safety communication from FDA on June 2 advising that "patients who experience moderate to severe pain at the Zecuity patch site should immediately remove it to avoid possible burns or scarring, regardless of how long the patch has been worn, and contact your health care professional."

It's a stronger recommendation that the one in the product label, which does not include warnings of burning or scarring. Labeling advises removal of the patch if there is "a powerful burning sensation during use" and notes that application site pain is one of the most common adverse reactions.

The patient information section notes under "important information" for the Zecuity transdermal system (TDS) that "you may feel slight tingling or a mild burning sensation within 30 seconds of activating the Zecuity TDS."

The labeling notes that no more than two Zecuity patches should be used in any 24 hour period, a second patch should be used no sooner than two hours after activation of the first patch, and the patch should not be applied to a previous application site until that site remains erythema free for at least three days.

Despite the limited discussion in labeling, rashes and scars were a concern for FDA during the review. The approval letter states, "We request that any case of skin burn and any case of scar at the site of administration be submitted as a 15-day report," the most serious kind of adverse event alert.

Teva issued a "Dear Health Care Provider” letter June 10 informing prescribers of the market suspension and recall. "Patients described severe pain, itching or burning," the letter says. "Although many cases resolved within hours to weeks, there are reports of cases with unresolved skin reactions, typically skin discoloration, after several months."

Zecuity Has Been Part Of Teva's Pain Focus

Teva acquired Zecuity with its $144m acquisition of NuPathe Inc. in 2014 and launched the pain treatment patch in September 2015. NuPathe received FDA approval of Zecuity in January 2013 but waited to commercialize the drug until it found a partner.

Approval had been delayed when FDA issued a "complete response letter." NuPathe said FDA had questions primarily about chemistry, manufacturing and safety, but did not elaborate as to what they were (Also see "NuPathe Must Patch Together New Zelrix Launch Timetable After "Complete Response" Letter" - Pink Sheet, 30 Aug, 2011.).

The acquisition of Zecuity was part of Teva's strategy to focus on pain and respiratory disease as its core therapeutic areas. The company said at the time that it wanted to be one of the three leading global players in the pain space (Also see "Teva Shoots For Top Three In Pain And Respiratory" - Pink Sheet, 4 Aug, 2014.).

Although it did not disclose sales for Zecuity in its first quarter earnings report, the company noted the revenue for its three other CNS medicines for the three months ended March 31: Copaxone (glatiramer) had $1b; Azilect (rasagiline), $113m, and Nuvigil (armodafinil), $103m.