Transcept Aims To Refile Intermezzo Insomnia NDA In Late Q4 With Highway Driving Data

FDA approved a resubmission plan that responds to concerns about inadvertent re-dosing and next-day driving impairment raised in an October "complete response" letter.

FDA approved a resubmission plan for Transcept Pharmaceuticals' insomnia drug Intermezzo that involves new packaging to foil inadvertent re-dosing and a next-day highway driving study to satisfy concerns the agency raised in a "complete response" letter, the company said March 24. The filing is targeted for late in the fourth quarter.

Intermezzo is a low-dose sublingual tablet form of zolpidem (Sanofi-Aventis' Ambien and generics) that potentially could be taken in the middle of the night when an insomnia episode occurs, rather than before bedtime when patients have to guess whether they might awaken.

However, Transcept faces the double challenge of fuzzy-minded patients accidentally taking the drug twice in one night and of them taking it when they no longer have four hours left to devote to sleep. Both concerns were the subject of a "complete response" letter FDA issued to the Point Richmond, Calif., specialty pharma in October 2009 (Also see "Transcept's Intermezzo Yields To FDA Concerns Over Residual Side Effects" - Pink Sheet, 29 Oct, 2009.).

Restricting Bleary Insomniacs To One Dose

Transcept may have solved the dosing problem already. Intermezzo's new unit dose packaging is designed to reinforce patient instructions and reduce the possibility of patient dosing errors, Transcept CEO Glenn Oclassen said March 23 during the firm's 2009 year-end earnings call.

FDA agreed in a Jan. 20 meeting that the revised packaging appeared to reduce the potential for inadvertent dosing errors, he said. However, the agency also suggested that conducting a patient-use study to evaluate whether patients can follow dosing instructions in the middle of the night under actual end-user conditions would be an additional way to address the concern, Oclassen added.

Agency concerns also remained about the possibility of patients taking the insomnia remedy too close to arising, Oclassen said. Transcept followed up in February with its plan for an impaired driving study, and the company announced March 24 that it had the go-ahead from FDA.

Regarding the patient-use study, FDA said it will "consider Transcept's position regarding the challenges and limitations of a pre-approval patient use study," according to the announcement. Transcept said it does plan to submit data from ongoing studies of patient comprehension of label instructions.

Testing Next-Day Driving Impairment

Transcept tapped the impaired-driving studies expertise of the University of Maastricht in The Netherlands to conduct the trial. Approximately 36 adults will be enrolled in the single center, double-blind, randomized, placebo-controlled crossover study, which compares the effects of Intermezzo 3.5 mg against placebo at three hours and four hours post-dose.

A control arm will compare 7.5 mg zopiclone against placebo. Zopiclone is a generic non-benzodiazepine hypnotic agent marketed outside the U.S. for insomnia. Its active stereoisomer, eszopiclone, is sold in the U.S. as Lunesta by Sepracor.

The primary endpoint of the study is "deviation of lateral position" (swerving or weaving) compared to placebo during highway driving measured over one-hour.

Can Transcept Afford The Resubmission Plan?

During the earnings call, Tom Soloway, Transcept's chief financial officer, assured investors the company has resources to manage the resubmission. Transcept had $88.9 million in cash, cash equivalents and marketable securities on hand at the end of the year.

A licensing and commercialization agreement with Purdue Pharmaceutical Products, signed in August, brought in an initial $25 million payment Transcept is recognizing over a 12-month period. The agreement includes the possibility of up to $30 million more depending on the timing of the approval and $90 million more based on milestones, plus double-digit royalties up to the mid-20 percent level ([See Deal]). Transcept retained an option to co-promote Intermezzo to psychiatrists in the U.S. and commercialization rights for the rest of the world.

The firm is in discussions with European regulators and is "encouraged by the prospects" for a pathway to approval, Oclassen said. Discussions with potential development and commercialization partners outside the U.S. also are "proceeding in a satisfactory manner," the CEO said.

Meanwhile, a competitor in the sleep maintenance market, Somaxon Pharmaceuticals, recently received FDA approval for its sleep aid Silenor (doxepin), although it also suffered regulatory setbacks. Somaxon hopes to launch in the second half, but it is low on cash and still seeking a commercialization partner (Also see "Somaxon's Silenor Gains An FDA Approval, But Can The Pharma Afford A Launch?" - Pink Sheet, 18 Mar, 2010.).

Silenor is not a controlled substance, while zolpidem is, and that may offer a competitive advantage. However, marketers should beware: Takeda got a brushback this month from FDA for touting its insomnia drug Rozerem 's lack of controlled substance scheduling as a superiority claim (Also see "Takeda's Rozerem Substance Abuse/Toxicity Claims Draw FDA Rebuke" - Pink Sheet, 24 Mar, 2010.).

-Shirley Haley ([email protected])