The launch of migraine patch Zelrix has been delayed beyond the first half of 2012 after FDA issued a "complete response" letter with manufacturing and other questions.

The move, which did not appear to be expected, seems to be more proof that companies cannot expect a slam-dunk approval for a reformulation of an already-approved drug.

NuPathe Inc. is planning to market Zelrix, a transdermal sumatriptan patch, as a treatment for migraine-related headache pain, nausea and light and sound sensitivity. The patch is expected to help patients who avoid oral migraine medications because of the associated nausea.

The company announced Aug. 30, the day after Zelrix's user fee goal date, that it had received the "complete response" letter. It said in a =statement questions remained primarily about "chemistry, manufacturing and safety."

NuPathe said it believes it "has, or shortly will have," the data needed to answer the questions. It also indicated additional Phase I and/or non-clinical studies could be necessary to address other questions.

FDA acknowledged in the letter efficacy had been demonstrated in the overall migraine population, according to the statement.

Company officials would not elaborate on what other questions the trials may be required to answer or provide a projected new launch date. NuPathe will request an end-of-review meeting with FDA to talk about addressing the outstanding issues, it said in the statement.

The agency's concerns about manufacturing are interesting given the increased flexibility FDA is offering sponsors in a recently-finalized guidance on patch GMPs (Also see "Drug Patch Manufacturers Can Skip Quality By Design Approach, FDA Says" - Pink Sheet, 24 August, 2011.).

Aspire Deal "Not A Signal"

The company announced Aug. 2 that Aspire Capital Fund LLC had committed to purchase up to $30 million of NuPathe stock over the next two years. Aspire's initial $500,000 investment bought nearly 71,000 shares at a 19% premium over the $5.95 per share closing price that day, NuPathe said in a written statement announcing the deal.

NuPathe stock closed at $2.65 per share Aug. 30, down more than 34% for the day.

NuPathe said the funding would be used to build financial strength and flexibility as it prepared to launch Zelrix. The company now may be forced to use a portion of the investment to fund additional trials and other activities related to the "complete response."

Keith Goldan, NuPathe vice president and chief financial officer, said during an Aug. 15 earnings call with analysts the company "was not trying to signal anything," with the timing of the deal's announcement.

"Notwithstanding the timing around PDUFA, or expected approval of the product, we just believed it was good corporate housekeeping to get the deal in place," Goldan said.

NuPathe also did not indicate any approval problems had emerged during the conference call. During the call and in its earnings release, the company announced it presented study data at the International Headache Society Congress showing Zelrix maintained a consistent efficacy and safety profile with repeat use over 12 months and patients showed "very low incidence of triptan-related adverse events," according to the Aug. 15 written statement.

Zelrix was expected to be one of a handful of migraine reformulations to enter the market soon. Among them was OptiNose's sumatriptan intranasal powder, expected to reach the market in 2012 (Also see "Allergan And MAP Team Up On Inhalable Migraine Treatment" - Pink Sheet, 31 January, 2011.).

Reformulations Of Me-Toos Not An Easy Sell To FDA

The Zelrix case is another example of reformulations of already approved drugs running into trouble at FDA. Transcept Pharmaceuticals' collaboration with Purdue Pharmaceutical Products to develop and commercialize Intermezzo, a sublingual formulation of the insomnia drug zolpidem, was left in doubt after the agency issued a second "complete response" letter for the drug.

The CR meant Transcept was unlikely to meet necessary deadlines associated with milestone and marketing payments from Purdue (Also see "Second Intermezzo "Complete Response" Threatens Transcept's Partnership Payments" - Pink Sheet, 15 July, 2011.).

- Derrick Gingery (d.gingery@elsevier.com)

NuPathe Must Patch Together New Zelrix Launch Timetable After "Complete Response" Letter

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