Oral NKTR-118 has low risk for mediating significant drug-drug interactions

Sep 14 2009

Nektar Therapeutics (Nasdaq: NKTR) presented clinical study data today demonstrating that the oral tablet formulation of NKTR-118 has favorable systemic bioavailability and a low risk for mediating significant drug-drug interactions. NKTR-118, an oral peripherally-acting opioid antagonist, is in clinical development for the treatment of opioid-induced constipation. These findings were presented today at the 38th Annual American College of Clinical Pharmacology (ACCP) Meeting in San Antonio, Texas.

Oral NKTR-118 combines Nektar's advanced small molecule polymer conjugate technology platform with naloxol, a derivative of the opioid-antagonist drug, naloxone. Nektar's proprietary advanced polymer conjugate technology increases the bioavailability and half-life of naloxol, enabling NKTR-118 to act selectively in the periphery while preserving centrally-mediated opioid analgesic clinical benefits.

"The data reported today, in combination with our strong Phase 2 clinical results, support advancing the oral tablet formulation of NKTR-118 into pivotal Phase 3 studies. NKTR-118 is an excellent example of how our novel advanced polymer conjugate platform improves oral bioavailability and enables preferential distribution of a drug within the body," said Lorianne Masuoka, M.D., Chief Medical Officer of Nektar. "By significantly improving the pharmacological activity of small molecule drugs, we are building an impressive portfolio of innovative treatments for diseases with high unmet needs."

A human pharmacokinetic study conducted in 20 healthy subjects demonstrated the comparative bioavailability of NKTR-118 in tablets and solution, confirming the drug's rapid absorption profile in both formulations and demonstrating the bioequivalence of the oral tablet formulation to solution. In vitro studies demonstrated the high metabolic stability of NKTR-118 compared to naloxone. Results of in vitro testing indicate that NKTR-118 has a low potential for clinically important drug-drug interactions, thereby facilitating the combination of NKTR-118 with a wide range of drugs in clinical development.

NKTR-118 Phase 2 Clinical Trial Data to be presented in Oral Plenary Session at ACG 2009

Nektar also announced today that results from a separate Phase 2 clinical trial of NKTR-118 have been accepted for presentation at an oral plenary session of the American College of Gastroenterology (ACG) 2009 Annual Scientific Meeting to be held in San Diego on October 27, 2009. The data will be presented by Dr. Lynn Webster, medical director of Lifetree Clinical Research and lead clinical investigator of the Phase 2 trial.

Topline data from this Phase 2 study showed that NKTR-118 met the primary endpoint of increase in spontaneous bowel movements over the baseline period in a double-blind, randomized, placebo-controlled study in 208 patients with opioid-induced constipation, while preserving the analgesic effect of opioid by reducing the blood-brain barrier penetration.

Download Today's Data Presentations for NKTR-118

The poster presentations presented today at the ACCP 38th Annual Meeting (Poster Session 1, 6:00 - 8:00 PM Central time) can be found on Nektar's website at http://www.nektar.com/product_pipeline/cns_pain_oral_nktr-118and119.html

ACCP Poster #140: "NKTR-118, an oral peripheral opioid antagonist, has low potential for drug-drug interactions"

ACCP Poster #141: "Comparative bioavailability of NKTR-118 tablets and solution: a case of bioequivalence between dosage forms for a rapidly absorbed drug"

The corresponding abstracts for these presentations are published in the September 2009 issue of The Journal of Clinical Pharmacology (J. Clin. Pharmacol., Sept 2009; 49:1123).