TRIAL: Drug For The Treatment of Pain and Polycystic Kidney Disease

[okarol]

Plexxikon Initiates Phase 1 Trial for PLX5568 - First-in-Class Drug For The Treatment of Pain and Polycystic Kidney Disease

05 Sep 2008   

Plexxikon Inc. announced that it has initiated a Phase 1 human clinical trial for PLX5568, a novel kinase inhibitor targeted for the treatment of at least two major indications with unmet medical needs: pain as well as polycystic kidney disease (PKD). PLX5568 has demonstrated robust preclinical efficacy in multiple pain models, including neuropathic pain as well as acute and inflammatory pain. In addition, PLX5568 has demonstrated compelling efficacy in multiple preclinical models of PKD.

Dosing has been completed in the first cohort of healthy volunteer subjects in the single ascending dose, double-blind, placebo-controlled trial, which will enroll approximately 30 subjects. This study will be followed by a multiple ascending dose, double-blind, placebo-controlled trial, which will enroll approximately 32 healthy volunteer subjects. Together, these studies are being conducted to evaluate the safety and tolerability of PLX5568 as well as to gain insight into the pharmacokinetic profile of the drug candidate. Preliminary pharmacokinetic data from the Phase 1 trial indicate that the exposure in blood achieved with the initial dose is in the target range required to show efficacy with once-a-day capsule dosing.

"PLX5568 represents the fifth Investigational New Drug (IND) from our discovery platform to enter the clinic in four years, and expands our therapeutic portfolio now also to pain and renal disease with this first-in-class agent, underscoring our early development capabilities as well as the productivity and breadth of our discovery platform," stated K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. "Additionally, PLX5568 is a highly selective drug candidate and yet another example of Plexxikon's hallmark capability to design very selective kinase inhibitors. Given this capability, we are uniquely positioned to explore kinase drug candidates for the potential treatment of chronic indications where safety is paramount."

PLX5568 is a very selective and potent kinase inhibitor. Non-clinical GLP toxicology studies which included doses up to 2000 mgs per day over a period of 28 days, have confirmed the attractive safety profile of our selective kinase inhibitor, and that such selectivity potentially confers safety to our drug candidate. Kinases represent a large family of potential drug targets through which a broad range of chronic diseases could be treated with safe and selective drugs that inhibit their activity.

About PLX5568 in Pain

PLX5568 is a first-in-class, oral, non-opioid agent with opiate-like efficacy, and a rapid onset of action. Kinases play a key role in the signaling pathways that control the sensation of pain and the transmission of pain sensing signals. Preclinical efficacy in various types of pain models demonstrated clear analgesic responses to treatment with PLX5568, comparable to gabapentin or morphine even at low doses of PLX5568, but without the side effects of an opiate. Following the successful completion of the Phase 1 trial, Plexxikon plans to initiate a Phase 2 clinical trial in neuropathic pain patients in 2009.

As a non-opioid and oral pain agent, PLX5568 could address significant unmet needs in chronic pain, cancer pain and neuropathic pain, addressing substantial markets with an estimated 7.8 million patients with neuropathic pain alone. There is a significant opportunity for novel pain treatments, since most currently available pain therapies suffer from suboptimal efficacy, intolerable side effects or long-term safety concerns, including sedation and addiction.

About PLX5568 in Polycystic Kidney Disease

PLX5568 has also demonstrated impressive efficacy in orthologous models of both forms of PKD, including effects on cyst size and renal function. Following the successful completion of the Phase 1 trial and chronic toxicology studies, Plexxikon plans to initiate a Phase 2 clinical trial in PKD patients in 2009.

PKD is a genetic disease in which cysts form in the kidneys, causing them to become enlarged and infected, or burst, ultimately leading to loss of kidney function. Currently, there are no treatments for this disease, and patients eventually progress to kidney transplant or dialysis. PKD is the most common life-threatening genetic disease, affecting approximately 600,000 patients in the U.S. and over 12 million patients worldwide.

Plexxikon Profile

Plexxikon is a leader in structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease. The company's clinical stage programs include PLX204 for the treatment of diabetes, PLX4032 for the treatment of melanoma and colorectal cancer and PLX5568 for the treatment of pain and renal disease. Among the company's preclinical development programs, candidates are being developed for the treatment of rheumatoid arthritis, multiple sclerosis and other autoimmune diseases.

Plexxikon's proprietary Scaffold-Based Drug Discovery™ platform is being applied to build a pipeline of diverse product opportunities for the treatment of metabolic and cardiovascular disease, inflammation, oncology and CNS disorders. This discovery process integrates a number of state-of-the-art technologies, including structural screening as one key component that provides a significant competitive advantage over other drug discovery approaches. To date, the company has discovered a portfolio of clinical and preclinical stage compounds in multiple disease areas addressing significant unmet needs in each therapeutic category.

Plexxikon is seeking pharmaceutical and biotechnology partners for select collaboration opportunities.

Plexxikon

Article URL: http://www.medicalnewstoday.com/articles/120364.php