depression

Glutamate a big target for drug developers

Mon, 25 Feb 2008 06:59:56 -0500

The New York Times' Alex Berenson looks at the wave of new research programs focused on the neurotransmitter glutamate as a therapy for schizophrenia. Eli Lilly's Darryle D. Schoepp recognized its potential in the fall of 2006, and other drug discoverers weren't far behind as a number of developers jumped into the field. All approved therapies for schizophrenia target dopamine, and the glutamate connection opened up a host of possibilities for depression, Alzheimer's and other indications as well.

"I don't think people appreciate how much money, time and good technical research goes into what we do," Schoepp told the Times. "Sometimes, people think the idea is the thing. I think the idea can be the easy part."

- read the article from The New York Times

Related Articles:
Potential new drug found for schizophrenia. Report
Addex is talking deals as interest in a new class of drugs. Profile

Blogster sees lessons in FDA approvable letters

Thu, 21 Feb 2008 06:59:54 -0500

The blogster Eye on FDA has tracked down and posted every approvable letter he's heard about for 2007. The crop of letters highlights some particular challenges for new drugs targeting ADHD, pain and depression. The 29 letters marked a record for the FDA, particularly for multiple letters covering the same therapy. "And even though we are in a severe "risk-averse" environment, one could say that efficacy was every bit as much a factor as safety in the 2007 crop of letters."

- read the blog report

Related Articles:
2007 FDA approvals. Report
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'07 drug approval record raises worries. Report
Dry spell or parched desert for NME approvals? Report
New drug approval lags in 2007. Report

Northstar brain therapy fails late-stage trial

Tue, 22 Jan 2008 06:59:54 -0500

Northstar Neuroscience says that a brain stimulation therapy intended to improve hand and arm function in stroke victims flunked a late-stage trial. Northstar's treatment uses electrical stimulation to the brain, but it failed to improve limb function by 20 percent, the primary goal of the trial. Seattle-based Northstar says it is unlikely that the data warrants FDA approval for that, but adds that it still has potential for other conditions, including depression and tinnitus.

- see this release
- check out the AFX report

Biovail shares sink after FDA schedules review

Tue, 20 Nov 2007 06:59:55 -0500

Shares of Biovail took a dive this morning after the company announced that the FDA expects to take six months to review its application for BFV-033, a once-daily version of buproprion, which is sold as Wellbutrin for depression. Biovail says the new formulation has a better safety profile than the currently marketed therapy, but the company has been stymied in gaining an approval. The FDA issued a non-approvable letter last summer, though Biovail says it responded in October after reanalyzing its data. Biovail had been hoping for a quicker response from the agency. So did investors, who took a nine percent bite out of Biovail's stock price in retaliation for the disappointment. Sales of Biovail's extended release form of Wellbutrin plunged 57 percent against generic competition in the third quarter.

- see this release
- check out the AP report on Biovail

Related Articles:
FDA hands Biovail a non-approval letter. Report
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Biovail chairman charged with securities violations. Report
Biovail loses effort to stop generic Wellbutrin. Report
Biovail to spin off older drugs, start new pharma co. Report

FDA demands more data on Wyeth's Pristiq

Tue, 24 Jul 2007 06:59:58 -0400

Wyeth was effectively stiff-armed by the FDA in its application for Pristiq, the first non-hormonal therapy to treat menopausal symptoms. In an approvable letter, regulators told the company that they want to see a one-year safety study done to gather more data on how the drug could affect patients' hearts and livers. That amounts to a major delay for Wyeth, but the drug company shows no sign of backing away from the therapy.

"Wyeth remains committed to the development of Pristiq as a potential treatment for moderate-to-severe vasomotor symptoms associated with menopause," said Wyeth CMO Dr. Gary Stiles. "We will work with the agency, and we have not yet met with them, to satisfy its requests for additional data and move this medicine forward in the FDA review process."

- see the release
- check out the AP report for more

Related Articles:
Wyeth expects provisional OK for Pristiq. Report
FDA approves Pristiq for depression. Report

GlaxoSmithKline Statement - BBC Panorama

Maureen Martino — Mon, 29 Jan 2007 11:14:30 -0500

GlaxoSmithKline Statement - BBC Panorama

LONDON, Jan. 29, 2007 - This statement has been issued in anticipation of the BBC Panorama programme, ‘Secrets of The Drugs Trials’ which is to be aired on Monday 29th January.

GlaxoSmithKline (GSK) has provided a written response to the allegations it understands are to be made in the above programme. GSK has not seen the programme but strongly denies suggestions that it has acted in any way improperly. The company has no confidence that its responses will be accurately, or appropriately, represented in the programme, or in the BBC’s publicity materials. GSK therefore wishes to make the following points that include a summary of the information provided to the programme:

· We are extremely concerned that Panorama, will again, through misleading and deliberately provocative commentary, alarm patients about using their anti-depressant medication, with potentially serious consequences.

· Patients concerned by issues raised in the programme should seek advice from their doctor.

· Depression is a severe and disabling condition. A well-recognised, tragic outcome of the disease, particularly among young people, is suicide. Careful monitoring of all patients is essential, regardless of whether they are taking medication or not.

· In developing Seroxat, GSK has always been strongly conscious of the duty it owes to the millions of patients, including those under the age of 18, who suffer from depression and we refute any allegation that we have failed in this duty. GSK conducted nine studies, over eight years, to examine the use of Seroxat in treating patients under the age of 18 with depression and other psychiatric disorders, as treatment options for these vulnerable patients are extremely limited.

· GSK utterly rejects any suggestion that it has improperly withheld drug trial information. Results from its paediatrics studies were documented and submitted to regulators in accordance with regulatory requirements. Results were also presented publicly, published in scientific journals and are available on GSK’s website.

· No suicides were reported in any of the nine paediatric trials conducted by GSK. When reviewed individually, none of these trials were considered by GSK or independent investigators to show a clinically meaningful increase in the rate of suicidal thinking or attempted suicide. Only when all the data became available, at the end of the research programme, and were analysed together was an increased rate of suicidal thinking or attempted suicide revealed in those paediatric patients taking Seroxat . GSK brought this analysis to the attention of the regulatory authorities, including in the UK.

· GSK does not promote its medicines for indications for which they are not approved.The company strongly refutes any suggestion that Seroxat was promoted to UK doctors for use outside the terms of the UK marketing authorisation, whether through clinical experts (“Key Opinion Leaders”) or any other route.

· Seroxat has never been approved by EU or US regulators as a medicine for those under 18 years of age. GSK’s UK product labelling has been entirely consistent with that position, and at the time of the events in question, this label stated: “the use of Seroxat in children is not recommended, as safety and efficacy have not been established in this population.” Any decision to prescribe a medicine outside its authorised indications, in the EU or the US, is made by a doctor on the basis of his/her clinical judgement and the interests of their patient.

· GSK, in 2004, further demonstrated its commitment to data transparency by creating an unsurpassed on-line database, called the Clinical Trial Register (CTR). This is a record of detailed summaries of more than 2,800 clinical trials conducted in 50 countries to study 52 GSK prescription medicines and vaccines which is available to the public at http://ctr.gsk.co.uk

Press Release: XTL Biopharmaceuticals And DOV Pharmaceutical In Deal Valued At More Than $130

Maureen Martino — Tue, 16 Jan 2007 11:26:02 -0500

XTL Biopharmaceuticals And DOV Pharmaceutical In Deal Valued At More Than $130 Million For Pain Killer

NEW YORK, January 16 -- XTL Biopharmaceuticals Ltd. announced today that, through a wholly-owned subsidiary, it has signed an agreement with DOV Pharmaceutical, Inc. (PS: DOVP.PK) to in-license the worldwide rights for Bicifadine, a serotonin and norepinephrine reuptake inhibitor (SNRI).

XTL intends to develop Bicifadine for the treatment of neuropathic pain - a chronic condition resulting from damage to peripheral nerves. With 15 million people suffering from neuropathic pain in the United States alone, and limited treatment options available, neuropathic pain represents a significant unmet medical need. According to Datamonitor, the market for neuropathic pain drugs is expected to grow from $1.8 billion in 2005 to $5.5 billion by 2015.

Bicifadine is a serotonin and norepinephrine reuptake inhibitor (SNRI). Other members of the SNRI class include Cymbalta(R) (approved for depression and neuropathic pain), and Effexor(R) (approved only for depression). Both Cymbalta(R) and Effexor(R) have been shown to be efficacious in neuropathic pain. Activity on norepinephrine reuptake is thought to be necessary for anti-depressants to be effective in neuropathic pain.

Compared to the currently approved SNRI's, Bicifadine has a unique ratio of serotonin versus norepinephrine reuptake inhibition, which is weighted toward norepinephrine reuptake inhibition, providing a strong scientific rationale for using Bicifadine for the treatment neuropathic pain indications.

Bicifadine has been tested extensively in over 15 clinical trials involving over 3,000 patients, and has been shown to be safe and generally well tolerated. Bicifadine was evaluated in various pain indications, including two large, randomized clinical trials (n=750 and n=540) in patients suffering from acute (non-neuropathic) pain, where Bicifadine demonstrated statistically significant efficacy.

Dr. Christine Sang, Director of Translational Pain Research at the Brigham and Women's Hospital, Harvard Medical School, commented, "Neuropathic pain continues to be an area of growing unmet medical need, and I believe that Bicifadine represents an exciting potential treatment option. Clinical data clearly support the role of SNRI's for the treatment of neuropathic pain. Based on its mechanism of action that includes a unique ratio of serotonin versus norepinephrine reuptake inhibition, the demonstrated effect of other SNRI's in this disease area, and the activity it has demonstrated in acute pain studies, I have a high degree of confidence that Bicifadine could be successfully developed as a treatment for neuropathic pain."

Ron Bentsur, XTL's Chief Executive Officer, commented, "This is a very important event for XTL, as this in-license transforms us immediately into a late-stage development company. It is rare to come across an opportunity such as Bicifadine, a drug candidate that addresses a multi-billion dollar market, in a class with a proven mechanism of action, and with an established safety profile and clear evidence of activity in the treatment of pain." Mr. Bentsur added, "By re-directing the development of Bicifadine away from the novel indications in acute and chronic pain toward a proven area of efficacy of SNRI's in the treatment of neuropathic pain, we believe we can be the second approved SNRI for neuropathic pain, offering a differentiated efficacy and possibly safety profile based on the drug's emphasis on norepinephrine reuptake inhibition. We are excited to bring Bicifadine on board as our lead compound."

In accordance with the terms of the license agreement, XTL will make an up-front payment of $7.5 million in cash. In addition, XTL will make milestone payments of up to $126.5 million, in cash and/or XTL ordinary shares over the life of the license, of which up to $115 million will be due upon or post approval of the product. XTL is also obligated to pay royalties on net sales of the product to DOV. In addition, the Company has committed to pay a transaction advisory fee in the form of stock appreciation rights in the amount equivalent to 3% of the Company's current fully diluted ordinary shares, vesting after one year of the close of the transaction, and 7% of the Company's current fully diluted ordinary shares, vesting following successful Phase 3 clinical trial results or the acquisition of XTL. Payment of the stock appreciation rights by XTL can be satisfied, at XTL's discretion, in cash and/or by issuance of the Company's ordinary shares.

ABOUT BICIFADINE

Bicifadine is a serotonin and norepinephrine reuptake inhibitor (SNRI) being developed by XTL for the treatment of neuropathic pain. Bicifadine was licensed by XTL from DOV Pharmaceutical, which originally licensed it from Wyeth Pharmaceuticals.

Four Phase 1 clinical trials and 14 Phase 2 clinical trials involving more than 1,000 patients were conducted by Wyeth or DOV with an IR (immediate release) formulation of Bicifadine. In five exploratory double-blind, placebo-controlled Phase 2 clinical trials of the IR formulation conducted by Wyeth, Bicifadine demonstrated a statistically significant reduction in pain versus placebo, in some cases with an outcome suggesting it might be comparable to or better than positive controls such as codeine. In addition to these trials with the IR formulation, eight Phase 1 clinical trials using the SR (sustained release) formulation have been conducted, a formulation that permits less frequent daily dosing, improves tolerability and for which patents have been filed. It is intended that the SR formulation will be used in future clinical development and for commercial use

In two additional and larger (n=750 and n=540) single-dose, double-blind, placebo-controlled clinical trials with Bicifadine in the treatment of moderate to severe post-surgical acute dental pain, Bicifadine produced a highly statistically significant, dose-related reduction in pain compared to placebo, and which was comparable to a positive control arm (codeine or Tramadol). Both trials demonstrated Bicifadine to be safe and generally well-tolerated without producing any serious adverse events.

In a Phase 3 double-blind, placebo-controlled, clinical trial (n=325) with Bicifadine in the treatment of moderate to severe acute pain following bunionectomy surgery, statistically significant increases in analgesia were measured as early as 30 minutes after administration and these effects were sustained for the balance of the eight-hour measurement period. In this study, Bicifadine was safe and generally well-tolerated. The complete assessment of the analgesic action of Bicifadine under repeat dosing conditions could not be fully elucidated due to the high level of "rescue" analgesic medication used in both the placebo and active drug groups.

Due to the highly competitive nature of the market for acute pain drugs, and the FDA requirement to complete two repeat-dosing clinical trials in two different acute pain indications, no further studies in acute pain are planned.

Bicifadine has been further evaluated in three Phase 3 trials in Chronic Lower Back Pain (CLBP). The primary efficacy endpoint in these trials was the change in pain severity rating score between baseline and the end of dosing. In these trials, Bicifadine was safe and generally well tolerated, but did not show a statistically significant effect relative to placebo on the primary endpoint of the study at any of the doses tested.

XTL believes that the failure of Bicifadine in the CLBP trials was a result of the inherent heterogeneity of the studied patient population (i.e. the varying causes of CLBP pain), uncontrolled physical activities in what is largely an activity-dependent pain indication, and a high placebo response.

XTL believes that by re-directing the development of Bicifadine away from the novel indications in acute and chronic pain toward a proven area of efficacy of SNRI's in the treatment of neuropathic pain, Bicifadine could be successfully developed to be the second approved SNRI for neuropathic pain, offering a differentiated efficacy and possibly safety profile based on the drug's emphasis on norepinephrine reuptake inhibition.

ABOUT XTL BIOPHARMACEUTICALS LTD.

XTL Biopharmaceuticals Ltd. ("XTL") is engaged in the acquisition, development and commercialization of therapeutics for the treatment of neuropathic pain and hepatitis C. XTL is developing Bicifadine, a serotonin and norepinephrine reuptake inhibitor, for the treatment of neuropathic pain. In addition, XTL is developing XTL-2125 - a small molecule, non-nucleoside inhibitor of the hepatitis C virus polymerase. XTL-2125 is currently in a Phase 1 clinical trial in patients with chronic hepatitis C. XTL is also developing XTL-6865 - a combination of two monoclonal antibodies against the hepatitis C virus - presently in Phase 1 clinical trials in patients with chronic hepatitis C. XTL's hepatitis C pipeline also includes several families of pre-clinical hepatitis C small molecule inhibitors. XTL also has an active in-licensing and acquisition program designed to identify and acquire additional drug candidates. XTL is publicly traded on the NASDAQ, London, and Tel-Aviv Stock Exchanges .

Contact:

Ron Bentsur, Chief Executive Officer

Tel: +1-(212)-531-5960

Cautionary Statement Some of the statements included in this press release, particularly those anticipating future clinical and business prospects for our clinical compound for neuropathic pain, Bicifadine, operating strategies and similar matters, may be forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Among the factors that could cause our actual results to differ materially are the following: our ability to successfully complete cost-effective clinical trials for the drug candidates in our pipeline which would affect our ability to continue to fund our operations with our available cash reserves, our ability to meet anticipated development timelines for the drug candidates in our pipeline due to recruitment, clinical trial results, manufacturing capabilities or other factors; and other risk factors identified from time to time in our reports filed with the Securities and Exchange Commission and the London Stock Exchange, including our annual report on Form 20-F filed with the Securities and Exchange Commission on May 25, 2006. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not intend to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at http://www.xtlbio.com. The information in our website is not incorporated by reference into this press release and is included as an inactive textual reference only.

XTL Biopharmaceuticals Ltd
CONTACT: Contact: Ron Bentsur, Chief Executive Officer, Tel:+1-(212)-531-5960

Epix anxiety drug fails in late-stage trial

Thu, 21 Sep 2006 20:01:36 -0400

Shares of Epix Pharmaceuticals slipped after the developer announced that a late stage trial of its experimental long-acting drug for general anxiety disorder failed to achieve a statistically significant response compared to a placebo. PRX-00023 was tested in a Phase III trial that enrolled 310 patients. "Based on these top-line results, we plan to refocus our efforts away from anxiety to evaluate the benefit in depression more closely and assess opportunities for initiating a Phase II clinical trial in depression sooner than originally planned," said Chief Executive Dr. Michael G. Kauffman, in a statement.

- check out the AFX article for more on the trial

Dapoxetine proves effective in clinical trial

Thu, 07 Sep 2006 20:01:36 -0400

ALZA's dapoxetine demonstrated its safety and efficacy in a new clinical trial. Researchers at the University of Minnesota concluded that the study of 2,600 men increased the average duration of intercourse from less than a minute to three minutes and 19 seconds. If the drug is eventually approved, it would be the first therapy on the market specifically for PE and likely to enjoy a large market. Dapoxetine is an SSRI drug, a category that is typically used to treat depression. This particular formulation, though, was designed specifically to treat PE, a condition that affects about a third of all men. The data from the study is outlined in an article in The Lancet.

- here's the BBC's report on dapoxetine

EPIX to buy Predix in $90M merger

Sun, 02 Apr 2006 20:01:39 -0400

EPIX Pharmaceuticals has inked a deal to buy Predix Pharmaceuticals in a deal valued at $90 million. Predix shareholders will wind up with 47 percent of the company and stand to earn an additional $35 million in milestones. The combined drug developer will have several advanced programs, including PRX-00023 in Phase III for anxiety and expected to enter Phase II for depression in 2007; EP-2104R in Phase II for imaging arterial and venous blood clots; PRX-03140, which has completed Phase Ib trials and is expected to enter Phase II for Alzheimer's disease later this year and PRX-08066 in Phase Ib development for pulmonary arterial hypertension.

- here's the release for more information