Labopharm Receives Approvable Letter From FDA For Once-Daily Tramadol

Labopharm Inc. today announced that it has received an approvable letter from the U.S. Food and Drug Administration (FDA) for its once-daily formulation of tramadol.

In its letter, the FDA indicated that Labopharm's once-daily formulation of tramadol is approvable subject to the resolution of certain issues. The Company plans to discuss the letter with the FDA as soon as possible and believes that it can address the issues raised in the letter without the need for additional data. Potential outcomes with respect to resolution of the issues range from utilization of current data to the need to generate additional data.

"We plan to work closely with the FDA to resolve the outstanding issues and obtain final approval," said James R. Howard-Tripp, President and Chief Executive Officer, Labopharm Inc. "We will provide further information following discussions with the FDA and clarification of the path forward."

Labopharm's New Drug Application (NDA) [IND] for its once-daily formulation of tramadol was submitted to the FDA in November 2005. The NDA included data from the Company's global clinical development program including six Phase III clinical studies and 12 pharmacokinetic studies. Combined, more than 2400 patients have been exposed to the product in clinical studies.

What is tramadol?
ULTRAM is a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin.

Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabo-lite M1 to µ-opioid receptors. In animal models,M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in µ-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound (see CLINICAL PHARMACOLOGY, Pharmacokinetics).

Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro, as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of ULTRAM. Analgesia in humans begins approximately within one hour after administration and reaches a peak in approximately two to three hours.


so why the hell is the stock down? here's why-- "We're pretty confident. You're not done until you're done," James Howard-Tripp, Labopharm president and CEO, told Reuters.

"We have got it approved in other jurisdictions. We believe it's a good product. We believe in our data package, so we would be pretty optimistic."

Labopharm shares dropped almost 25 percent on Friday after the company said it had received an approvable letter from the U.S. Food and Drug Administration for its version of the tramadol pain killer, but that the FDA said there are some unresolved issues.

The shares were down C$1.69, or 20.8 percent, at C$6.42 on the Toronto Stock Exchange, after dropping as low as C$6.09 earlier in the day. On Nasdaq, the shares were off $1.56, or 21.3 percent, at $5.75 after earlier falling as low as $5.42.

Howard-Tripp said the company plans to discuss the letter with the FDA "fairly rapidly" and believes it can address the issues raised without the need for additional data.

Howard-Tripp refused to say what issues were flagged---yeah no sh*&!! Once daily opioid for severe pain? OK........
(TSX: DDS, NASDAQ: DDSS)