Nektar Therapeutics announced the preliminary topline results from a Phase 2 study of NKTR-181 for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis of the knee. The Phase 2 study utilized a double-blind, placebo-controlled, randomized withdrawal study design to assess the efficacy, safety and tolerability of NKTR-181. Of the 295 patients that entered the study, only 9 (3%) patients were unable to achieve meaningful pain relief with NKTR-181. Fifty-three (18%) patients discontinued treatment during the titration period because of adverse events, most of which are those commonly associated with opioids. A total of 213 patients achieved an average 40% reduction in pain and entered the randomized phase of the study.
Following the titration period, patients were randomized 1:1 to either continue to receive their analgesic dose of NKTR-181 or to receive placebo for 21 days. NKTR-181 performed as expected as an opioid analgesic throughout the study with patients continuing to show a reduction in pain scores throughout the randomized phase of the study as well. However, patients who were randomized to placebo did not show the expected increase in pain scores observed in similar enriched enrollment, randomized withdrawal studies. This unusual lack of a placebo rebound caused the Phase 2 study to miss the primary endpoint in the study, which was based upon the average change in a patient’s pain score from pre-randomization baseline to the end of the double-blind, randomized treatment period of the study.
“We are experiencing a major public health problem with prescription opioids in this country, and need to find new ways to address this problem,” said Dr. Lynn Webster, chief medical officer of CRI Lifetree. “I have worked with NKTR-181 since this new molecule entered the clinic, and I believe that NKTR-181 could be an important advance in analgesia, maybe even a breakthrough. Although this Phase 2 study did not achieve its primary endpoint, this is not uncommon in opioid development. What is important is that the large majority of patients in this trial were able to achieve meaningful and long-lasting pain relief from NKTR-181. Providing analgesia without the pronounced CNS effects and euphoria of standard opioids is the future of analgesic development.”
NKTR-181 was also well-tolerated over the entire treatment period. The most common adverse events observed for patients taking NKTR-181 were constipation (22.4%) and nausea (10.3%). Discontinuation for adverse events was 18% during the titration period with the most common adverse events cited for discontinuation of constipation (8.8%), nausea (4%) and somnolence (3%).
“The results from this Phase 2 trial provide a great deal of additional insight into the analgesic profile of NKTR-181 and will be invaluable as we continue the development of this molecule,” said Howard W. Robin, president and chief executive officer of Nektar Therapeutics. “We were very pleased that this drug clearly performs as an effective analgesic with only 3% of the patients who received NKTR-181 unable to titrate to meaningful pain relief. We are carefully evaluating the lack of post-randomization rebound in the placebo arm in order to design the optimal pivotal trials for this drug. Based upon the data from this trial, it is clear that NKTR-181 provides pain relief on par with existing opioids while achieving a very favorable safety profile that differentiates it from standard opioids. We are committed to bringing NKTR-181 to patients suffering from chronic pain.”
NKTR-181 is a novel mu-opioid agonist molecule designed to have a slow rate of entry into the brain to reduce the attractiveness of the molecule as a target of abuse and to reduce other CNS-mediated side effects, such as sedation and respiratory depression.
Date: September 26, 2013
Source: Nektar Therapeutics