Nektar Therapeutics announced that the first subjects were dosed in a new phase I clinical study to evaluate NKTR-181, the company's next-generation opioid analgesic candidate. NKTR-181 is being developed to effectively treat pain while addressing the abuse liability and serious CNS side effects associated with currently available opioid therapies.

The single-dose phase I study is assessing the pharmacokinetics, pharmacology, safety and efficacy of NKTR-181 in up to 75 healthy subjects. The primary objective of the phase I trial is to establish the effective analgesic dose range of NKTR-181 associated with minimal CNS side effects. The study is being conducted in the US and Nektar expects to complete the study in the second half of 2011.

NKTR-181 was uniquely designed to cross the blood-brain barrier at a substantially slower rate than other opioid therapies. With a reduced rate of entry into the CNS, NKTR-181 has the potential to greatly reduce the euphoria that underlies opioid abuse liability and dependence, as well as the serious CNS-related side-effects of respiratory depression and sedation. The unique molecular design of the polymer drug conjugate also prevents conversion of NKTR-181 into a rapidly-acting, more abusable opioid.

“New pain medicines are desperately needed that are as powerful as opioids, but without the usual serious risks such as respiratory depression and disabling sedation,” said Lynn R Webster, MD, Primary Investigator for the phase I study and medical director of Lifetree Clinical Research and senior consultant to Omega Pain Clinic in Salt Lake City, Utah. “A novel opioid therapy, such as NKTR-181, that also has the potential to reduce the psychopharmacologic effects associated with drug dependence provides great promise for all physicians looking for safer and more effective pain management, and could help to address the significant public safety threat posed by existing opioid drugs.”

Endpoints in the phase 1 study include standard measurements of pain relief and standard measurements of CNS effects, such as euphoria, respiratory depression and pupillary response.

“We are excited about the initiation of the NKTR-181 clinical programme,” said Dr Lorianne Masuoka, senior vice president and chief medical officer of Nektar. “NKTR-181 represents a major step forward for our emerging pipeline of innovative and important new medicines.”

A novel mu-opioid analgesic investigational drug candidate, NKTR-181 was created using Nektar's small molecule polymer conjugate technology. In addition to exhibiting a reduced rate of CNS entry while providing effective pain relief with fewer CNS-related side effects in preclinical studies, the unique molecular design of the polymer drug conjugate also prevents conversion of NKTR-181 into an abusable form of opioid.

As a result, NKTR-181 has the potential to be a highly effective analgesic with a favourable safety profile and reduced potential for abuse, misuse and diversion.

Pain is the most common symptom for which patients seek medical attention. According to the American Pain Society, the prevalence of chronic pain in the United States is estimated to be 35.5% or 105 million people.  Chronic pain costs more than $100 billion per year in direct healthcare expenditures and lost work time. Opioids are considered to be the most effective therapeutic option for pain and have over $10 billion a year in sales in the US alone. However, opioids cause significant problems for physicians and patients because of their serious side effects such as respiratory depression and sedation, as well as the risks they pose for addiction, abuse, misuse, and diversion.

The US Food and Drug Administration has cited prescription opioid analgesics as being at the centre of a major public health crisis of addiction, misuse, abuse, overdose and death. A 2010 recent report from the Centre for Disease Control and Prevention (CDC) notes that emergency room visits tied to the abuse of prescription painkillers is at an all-time high, having increased 111 percent over a five-year period.

Nektar Therapeutics is developing novel therapeutics based on its PEGylation and advanced polymer conjugation technology platforms. Nektar has a robust R&D pipeline of potentially high-value therapeutics in oncology, pain and other areas.