Valium / Diazepam News Blog

"We have been faced with many challenges this year and have been working tirelessly to determine how to address these challenges and offer our stakeholders a value-driven strategic plan," said Barbara Duncan, President and Chief Financial Officer of DOV. "We believe that our decision to focus on the development of products emanating from our core areas of research and early stage clinical programs will significantly reduce our cash burn while we continue to evaluate strategic options for the Company."

Currently, DOV has drug development programs that are at the preclinical, Phase I, Phase II and Phase III clinical stages. These include bicifadine (Phase III for analgesia), DOV 21,947 (entering Phase II for depression), DOV 102,677 (Phase I for alcohol abuse) and an active preclinical discovery program in reuptake inhibitors and GABA modulators. DOV, while continuing to develop these core research platforms, will reduce its in-house late stage clinical development expenditures.

DOV's reuptake inhibitor platforms, including TRIs (triple reuptake inhibitors), NEDs (norepinephrine and dopamine reuptake inhibitors), and SADs (serotonin and dopamine reuptake inhibitors) have been tailored to treat a wide variety of neuropsychiatric disorders ranging from depression and attention deficit hyperactivity disorder to pain and obesity. In addition to DOV 21,947 and DOV 102,677, the Company has several molecules in various stages of preclinical development.

The primary objective of the GABA modulator program remains the development of a molecule producing a robust anti-anxiety action without the side effects associated with benzodiazepines such as diazepam (Valium(R)). Several molecules fitting this profile are in various stages of preclinical development. Further, GABA modulators also have proven utility as sedative- hypnotics, anticonvulsants, and muscle relaxants, and the Company has discovered several unique structural platforms that may be developed for these indications.

"DOV has deep scientific expertise in both the reuptake inhibitor and GABA modulator platforms and it is our objective to identify and bring forward the most promising clinical candidates in these core research areas," said Dr. Phil Skolnick, Executive Vice President and Chief Scientific Officer of DOV.

DOV is also announcing today that it has notified Merck of its desire to terminate the companies' license agreement with respect to DOV 21,947. As a result of this notification and in the event Merck decides not to re-internalize DOV 21,947, DOV will regain all rights to the compound, which will help the Company to increase its focus on its reuptake inhibitor program and also enable DOV to pursue broad partnership opportunities with respect to this program as part of its new strategic direction. As Merck notified DOV that it did not intend to select a preclinical compound licensed for evaluation under the amendment to the license agreement, all rights and data from those compounds will be returned to DOV effective immediately. DOV has asked Merck to notify the Company by December 8, 2006 about Merck's decision regarding the re-internalization and assumption of all development and other rights and obligations in the license agreement with respect to DOV 21,947. In the event Merck decides not to re-internalize the compound, DOV 21,947 will no longer be covered by the license agreement effective as of December 8, 2006. Unless terminated by Merck, the license agreement will remain effective in respect to DOV 216,303.

DOV will continue to seek a partner to further develop bicifadine, which has been shown to be effective in treating pain in three placebo-controlled efficacy trials in more than 1,600 patients with acute post-surgical pain. DOV also has conducted three substantial Phase III clinical trials of bicifadine in Chronic Low Back Pain (CLBP) and one early Phase II trial of bicifadine in osteoarthritis, all of which have provided the Company with a significant amount of data about the efficacy and safety of the drug. Bicifadine has demonstrated an attractive safety profile in short- and long- term safety studies involving more than 3,000 patients. Also, DOV has completed lifetime carcinogenicity studies in rats and mice with no meaningful signals of carcinogenicity detected after two years of testing, an outcome that DOV expects to be acceptable to the FDA.

DOV is holding discussions with potential partners for the further development and commercialization of bicifadine. DOV is working towards structuring licensing terms with potential partners utilizing the new information gathered from the Company's clinical trials of bicifadine -- the placebo-controlled Phase III trial, study 021, and the Phase II osteoarthritis study. Descriptions of the clinical trial results from the interim analyses of these two studies are included in this press release.

In April 2006, DOV announced that the United States Patent and Trademark Office (USPTO) issued a Notice of Allowance for its patent application covering a new polymorphic, or crystalline, form of its proprietary compound bicifadine, a novel analgesic. Today, the Company announces that this patent has been formally issued by the USPTO. Such patent will run through at least 2024 for this distinct form of bicifadine, which is the same form used in DOV's clinical trials and bicifadine development program.

DOV retains its license relationship with Neurocrine for the development of indiplon for the treatment of insomnia. Through this partnership, DOV will receive a 3.5 percent worldwide royalty on any sales of indiplon. In September 2006, Neurocrine held an end-of-review meeting with the Food and Drug Administration (FDA) for the indiplon capsules New Drug Application (NDA). Neurocrine summarized the results of the FDA meeting as follows: the FDA requested that Neurocrine supplement the pharmacokinetic/food effect profile of indiplon (IR) capsules to include several meal types. Neurocrine announced that it will initiate such a study shortly after further consultation with the FDA and that no other clinical trials were requested for the re-submission. Neurocrine also announced that it will hold an end-of- review meeting with the FDA to discuss and clarify action items for indiplon (MR) tablets towards late October 2006.

DOV will meet with the NASDAQ Listing Qualifications Panel on October 19, 2006 to present its plan for regaining compliance with the $50 million market capitalization listing requirement set forth by The NASDAQ Global Market. DOV will continue to be traded on The NASDAQ Global Market until a determination is made by the NASDAQ Listing Qualifications Panel following the hearing. The Company will issue a press release once it receives the NASDAQ Listing Qualifications Panel decision.

In the event the Company does not remain listed on a U.S. national securities exchange, the Company will be required to offer to repurchase the Company's $70 million outstanding convertible subordinated debentures.

Study 021 is a double-blind, placebo-controlled trial of bicifadine in patients with chronic low back pain (CLBP). After reviewing the detailed analysis of its first Phase III trial of bicifadine in CLBP -- study 020 -- DOV announced that it amended the inclusion criteria and simplified the dosing regimen of this second ongoing Phase III trial -- study 021 -- of bicifadine in CLBP to better position the trial for a successful outcome. Study 021, therefore, was amended to analyze only patients with more severe CLBP, accompanied by pain radiating to the leg and/or substantial functional disability, and compare only two dosing arms, 400 mg of bicifadine versus placebo.

Study 021 has enrolled more than one half of the intended patients. DOV has recently elected to perform an interim analysis and to unblind the results to determine whether the baseline features of functional disability or back pain plus radiating leg pain would result in the selection of patients for whom the placebo response is low and the bicifadine effect is substantial. Additionally, DOV performed a meta-analysis of the combined study 020 (for which data was released in April 2006) and study 021 of bicifadine in CLBP patients, thus providing a larger sample size upon which to draw conclusions regarding the efficacy of bicifadine in CLBP.

The importance of radiating leg pain (Quebec Classification (QC) of 2 or 3 for low back pain) at baseline was observed as a predictor of a low placebo response in study 020, but did not replicate in study 021. Both the meta- analysis of the combined study results and the results of study 021 did not show statistically significant superiority for controlling low back pain in patients enrolled with these baseline characteristics. Thus, DOV no longer believes that this baseline factor of radiating leg pain is a basis for selecting patients for whom the placebo response is low in future trials.

However, the meta-analysis did demonstrate that for those patients with a moderate-to-severe level of dysfunction due to CLBP (Roland Morris Disability (RDQ) scores >17 at baseline), bicifadine showed statistically superior effects (p17 (n=219), DOV intends to meet with the FDA to discuss regulatory strategy and the scope of the future product labeling using this patient selection criterion. The Company believes this clarification will facilitate its bicifadine partnering efforts.

DOV has previously announced that enrollment in its Phase III open-label, long-term safety trial -- study 022 -- had been completed. To date, more than 175 patients have completed six months of dosing and more than 30 patients have completed a full year of treatment with bicifadine. There have been no deaths in the more than 3,000 patients who have received bicifadine in the clinical trial program. Further, there are no apparent safety risks in respect to cardiovascular safety and liver function, organ systems that are most commonly the cause of drug related safety concerns. As the safety database is no longer the gating item to an NDA filing and in order to further reduce cash burn, DOV has elected to stop dosing of all ongoing patients. This process and related regulatory close-out obligations at the study sites will take several months and is expected to be completed by early 2007.

DOV has performed an interim analysis of the results from the 29 patients who have completed all four dosing arms in its ongoing Phase II study of bicifadine in subjects with osteoarthritis of the hip or knee. This Phase II trial is the first study of bicifadine in patients with osteoarthritis. The trial, a multi-center, double-blind, placebo-controlled, four-way crossover trial in approximately 36 patients, is designed to assess the efficacy, tolerability and pharmacokinetics of bicifadine alone and in combination with ibuprofen. Dosing will be completed in mid-October.

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