Schizophrenia Daily News Blog

New Schizophrenia Medications in Early Testing - Update

The following are three brief summaries related to new medications currently in development for the treatment of schizophrenia. These are still in early phases of development and it will take as many as 3 or 4 years of testing before it is known if any of these medications will achieve FDA approval and be made available for the public. It will take even longer to understand what the side effects are of these medications. It is, however, positive news that many companies recognize the important unmet need for better treatments for schizophrenia - and are focused on trying to bring new treatments to market.

BioLineRx Ltd., an Israel-based drug development company, today announced the initiation of a Phase II clinical trial on schizophrenic patients for the maximal tolerated dose determination of BL-1020. BL-1020 is a first in class, orally available, GABA-enhanced antipsychotic for the treatment of schizophrenia.

"This is an important milestone in the history of BioLineRx and in the development of BL-1020," commented Morris C. Laster, MD, chief executive officer of BioLineRx. "The dose ranges in this Phase II trials are based on results in previous clinical studies, which were performed on healthy volunteers. Based on our previous results, we believe that BL-1020 has the potential to be clinically efficacious with minimal therapy-limiting side effects. We very much look forward for the results of these Phase IIa trials expected sometime during the fourth quarter of 2007."

The trial is designed as an open-label, multi-center, 6-week, sequential cohort study which is expected to be conducted in 5 centers in Israel and 12 centers in Romania. The primary objective of the study is to determine the maximal tolerated dose of BL-1020 in 60 patients with schizophrenia or schizo-affective disorder.

In preparation for the Phase II trial, BioLineRx held an international investigators meeting that was held in Jerusalem, Israel on June 14-18. Seventy psychiatric physicians and other clinical staff from total of seventeen sites in Romania and Israel participated in the meeting.

TorreyPines Therapeutics, Inc. today announced completion of its third Phase I clinical trial for NGX267, in clinical development for the treatment of cognitive impairment associated with schizophrenia (CIAS). The compound, a functionally selective muscarinic (M1) agonist, was found to be safe and well-tolerated when given orally to healthy male volunteers once-daily for four consecutive days. In two previous Phase I trials, NGX267, administered as single oral doses, was shown to be well-tolerated in healthy young adult males, as well as in healthy elderly males and females.

The purpose of the Phase I trial was to investigate the safety, tolerability and pharmacokinetics of multiple doses of NGX267 and to confirm data from previous studies in which NGX267 demonstrated evidence of muscarinic receptor stimulation as measured by increases in salivary flow. A total of 60 healthy males, between the ages of 18 and 55, were enrolled in the double-blind, placebo-controlled trial conducted at one center in Belgium. In a series of sequential dosing cohorts, subjects received a single oral dose of either 10, 20, 30 or 35 mg of NGX267 once-daily for four consecutive days. NGX267 was well tolerated at doses up to and including 30 mg, a dose range believed to be effective for treating memory and cognitive disturbances. TorreyPines plans to initiate a Phase II dose-ranging trial in CIAS during the first half of 2008.

A secondary objective was to obtain quantitative measures of salivary flow, prior to and at multiple time points post-dosing, as a peripheral biomarker for stimulation of the muscarinic receptor. In the study, increases in peak and total salivary flow were detected for NGX267 in comparison to placebo. These effects increased linearly with dose, were maintained over four days of dosing, and within subject peak increases in salivary flow correlated with peak plasma levels of NGX267.

Decreased salivary flow results in dry mouth, or xerostomia, and is a symptom of a number of underlying conditions. Causes of dry mouth include the autoimmune disorder Sjogren's Syndrome, radiation treatment to the head and neck, and HIV-related salivary gland disease. Xerostomia can also be a side effect of some medications and may be associated with aging.

"The data from this study are promising, given the low incidence of adverse events at potentially therapeutic doses for treating CIAS," said Neil Kurtz, M.D., President and Chief Executive Officer of TorreyPines. "In addition, the data not only confirm earlier findings that NGX267 increases salivary flow, but also demonstrates that the effect is seen at multiple dose levels and maintained after repetitive dosing. Moving forward, we now have data that suggests that this well-tolerated product candidate could be effective in treating not only CIAS, but also xerostomia. In addition to our planned Phase II study in CIAS, we will consider initiating a small proof of concept study for xerostomia early next year."

Targacept, Inc. - Winston-Salem, N.C., a clinical-stage biopharmaceutical company developing a new class of drugs known as NNR Therapeutics(TM), has initiated a Phase I clinical trial of TC-5619, a novel small molecule that modulates the activity of the neuronal nicotinic receptor (NNR) subtype known as alpha7. TC-5619 was discovered using Targacept's proprietary drug design technology known as Pentad(TM) and is the lead product candidate in its alpha7 NNR program.

"The entry of TC-5619 into the clinic further demonstrates the breadth and pharmacological diversity of our pipeline of NNR Therapeutics," said J. Donald deBethizy, Ph.D., Targacept's president and CEO. "The broad therapeutic application of the alpha7 NNR is well established and presents multiple opportunities for potential later stage development of TC- 5619. We are also excited by the promise of other alpha7 compounds in our portfolio."

The Phase I study is designed to evaluate the safety, tolerability and pharmacokinetics of TC-5619. The trial is a double-blind, placebo-controlled study with single escalating doses of TC-5619 administered orally to healthy volunteers.

The alpha7 NNR is associated with a variety of biological functions. In particular, the alpha7 NNR has been shown in animal studies to be an essential regulator of both inflammation arising from injury or infection and cognitive functions. Published in vitro studies have also suggested that the alpha7 NNR plays a role in protecting neuronal cells from deterioration and death, a process known as neuroprotection.