Logical Therapeutics Announces Positive Results Of LT-NS001 Vs. Naproxen Clinical Study

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Clinical Trials / Drug Trials;  Pharma Industry / Biotech Industry
Article Date: 28 Oct 2009 - 2:00 PDT

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Logical Therapeutics, Inc., a Waltham, MA-based biopharmaceutical company announced the positive results of a Phase I/II clinical trial evaluating the gastrointestinal (GI) safety of its investigational drug LT-NS001, the first of a new class of bio-activated prodrugs being developed for the chronic treatment of arthritic conditions. In the study, subjects receiving LT-NS001 experienced a 78 percent reduction in the rate of gastric ulcers, and fewer gastric and duodenal erosions, when compared with subjects receiving Naprosyn(®) (naproxen). The LT-NS001 prodrug is unique among non-steroidal anti-inflammatory drugs (NSAIDs) as it is pharmacologically inactive as a COX inhibitor in the GI tract, but once absorbed into the bloodstream, it is converted rapidly to naproxen. LT-NS001 has been engineered to reduce the GI safety risks associated with NSAIDs. Results were announced here at the American College of Gastroenterology's (ACG) Annual Scientific Meeting and presented by Jay L. Goldstein, MD, FACG, Professor of Medicine at the University of Illinois at Chicago, who was the lead investigator for the study.

"The positive results of this study challenge the conventional wisdom regarding NSAID-induced gastrointestinal injury, which physicians generally believe can be driven by systemic exposure to the drug. This study demonstrates that a novel mechanism for NSAID therapy, namely a bio-activated prodrug technology, can provide a significant level of improvement in GI safety, and that may be surprising to many physicians," said Peter A. Lankau, Chief Executive Officer of Logical Therapeutics. "This study brings us one step closer to fulfilling a significant unmet medical need for an NSAID with an improved GI toxicity profile and we look forward to continuing the clinical development of LT-NS001 with our next study scheduled to begin later this year."

Key Findings Presented at ACG

In this study, 120 normal volunteers aged 45 to 70 years received either LT-NS001 (n=61) or Naprosyn(®) (naproxen) (n=59) for seven days and underwent an upper GI endoscopy at baseline and on day seven to visualize the extent of GI injury. At the conclusion of the study, nine subjects (15.8%) had developed gastric ulcers while taking naproxen, compared with only two subjects (3.3%) on LT-NS001, a 78 percent reduction in the incidence of gastric ulcers (p=0.02). The total number of ulcers that developed in the naproxen arm was twenty-nine (29) compared to only three (3) in the LT-NS001 arm, leading to a significant difference in the mean number of gastric ulcers per subject (p=0.03). Additionally, subjects receiving LT-NS001 developed no duodenal ulcers. The primary endpoint for the trial, total modified gastroduodenal Lanza score (an indicator of GI injury) demonstrated less overall GI mucosal injury in the LT-NS001 subjects as compared to subjects receiving naproxen (p=0.03). Treatment emergent adverse events also favored LT-NS001 with no serious or severe adverse events, including fewer incidences of abdominal pain, gastritis and dyspepsia.

"The results of this initial study demonstrate a potential new approach to the treatment of patients who suffer from chronic painful diseases such as osteoarthritis with the use of an NSAID having the possibility of a lower incidence of GI side effects traditionally associated with naproxen," said Thomas J. Schnitzer, MD, PhD, Professor of Medicine, Internal Medicine/Rheumatology at Northwestern University Feinberg School of Medicine. "LT-NS001 has the potential to be a very valuable option for patients and health care providers if further studies with LT-NS001 demonstrate a reduced risk for NSAID-induced GI complications, a side effect which often results in discontinuation of arthritis therapy."

In the current study, LT-NS001 demonstrated comparable serum concentrations of naproxen at steady state, as measured by AUC and Cmax. Despite this equivalent systemic exposure to naproxen, a significant differential effect on mucosal injury rates was observed for the prodrug LT-NS001, which is pharmacologically inactive as a COX inhibitor until metabolized, as compared to naproxen.

About LT-NS001

LT-NS001 is the first in a new class of bio-activated prodrugs being developed for the chronic treatment of arthritic conditions. It is a novel, patented new chemical entity (NCE) prodrug of the non-steroidal anti-inflammatory drug (NSAID) naproxen, which has been engineered by Logical Therapeutics to significantly reduce the GI safety risks, including the formation of ulcers, associated with naproxen. LT-NS001 is unique among NSAIDs as it is pharmacologically inactive as a COX inhibitor in the GI tract, but once absorbed into the bloodstream, it is converted rapidly and quantitatively to naproxen. Naproxen is widely regarded as the NSAID with the most favorable cardiovascular safety profile among all of the drugs in this class.

Despite the availability of gastro-protective agents, serious NSAID-induced GI complications, such as hemorrhage and perforation, persist and are directly responsible for approximately 20,000 deaths in the U.S. each year. Older age and the need for regular NSAID therapy increase the risk of NSAID-induced GI complications.

Unlike other drugs currently in development which utilize a generic combination of an NSAID with a proton pump inhibitor (PPI) or a histamine-2 receptor antagonist (H2), LT-NS001 is a single agent, non-substitutable NSAID. The chronic administration of PPI's has been associated with serious side effects such as interference with anti-platelet treatments, increased susceptibility to infections and increased risk of bone fracture. LT-NS001 utilizes a proprietary technology which has demonstrated improved GI safety without the need for concomitant alkalinizing agents and their associated risks.

LT-NS001 is an investigational drug product candidate undergoing clinical evaluation and has not been approved by the U.S. Food and Drug Administration.

About Logical Therapeutics, Inc.

Based in Waltham, MA, Logical Therapeutics, Inc. is a venture-backed, privately held biotechnology company focused on the development of products that treat diseases associated with inflammation. The company is developing a novel platform of bio-activated prodrugs, covered by an intellectual property portfolio. LT-NS001, a naproxen bio-activated prodrug, is the Company's lead compound, with additional NSAID prodrug candidates in development. Each program addresses unmet medical needs in multi-billion dollar markets.

Source: Logical Therapeutics, Inc