Post Operative Pain: V1003
Summary
V1003 is a potent analgesic, tailored for the management of post-operative pain in hospital and home settings. It is a proprietary intranasal formulation of the µ-opioid agonist buprenorphine and it is envisaged that it will be prescribed in hospital after cessation of anaesthesia in sufficient quantity to allow the patient to manage their pain prior to discharge and at home, during the post-operative recovery period.
Buprenorphine is a well known analgesic and the intranasal formulation is being developed to provide rapid, effective relief of acute pain.
Background
There is a huge unmet medical need in the treatment of pain. There are an estimated 85 million people with chronic pain conditions in the US, with a further 193 million cases of acute pain each year. The use of pain medicines will expand significantly as medical advances continue to prolong lifespan. In contrast with many areas of medicine, there have been very few breakthroughs in the treatment of pain over the last two decades. The analgesics we use today are broadly of the same type that were used some 40 years ago, and remain limited in their efficacy and tolerability. $38 billion was spent worldwide on pain medication in the year 2002, forecast to grow to $75 billion by 2010. In recent years, the molecular pathology of pain has become better understood, confirming that pain is a complex set of disorders with many potential pathways for treatment. The discovery of new drug targets from this research has opened up the possibility of completely new classes of pain drugs.
Responding to economic pressures, the length of hospital stay after surgical procedures is reducing. This is driving an expansion in the requirement for strong, easy-to-use pain medicines with improved side-effect and safety profiles over those currently available. In the USA alone over 53 million patients undergo surgical procedures each year. Despite most patients receiving pain medication, 50-75% of patients report that they experience inadequate pain control (Datamonitor). Pain is the most commonly reported reason for readmission to hospital within 30 days of discharge or for admission directly after surgery. There is a substantial opportunity for novel and innovative medicines to expand and segment this developing market.
Clinical Studies
Two successful phase I clinical trials of V1003 have been conducted and have demonstrated rapid attainment of analgesic plasma levels. Buprenorphine is a well-known analgesic and the intranasal formulation has the potential to provide a convenient alternative to other treatments, allowing patients to manage their post-operative pain both prior to discharge from hospital and at home during their recovery period.
A Phase II clinical trial completed in March 2006 achieving its primary end point of pain relief over the period of eight hours from drug administration. The randomised, double-blind, placebo-controlled single dose Phase IIa study in 360 patients undergoing bunionectomy compared V1003 to both placebo and Vicodin®, one of the most widely prescribed oral pain killers.
A range of four doses of V1003 was investigated: 0.1, 0.2, 0.4 and 0.6mg. These were compared to Vicodin® (hydrocodone 10mg, paracetamol 1g) and placebo, with an equal number of patients in each of the six study groups. The results demonstrated that doses of V1003 of 0.2mg and above were statistically superior to placebo for the primary end point. A dose response was demonstrated for V1003 and the highest dose tested (0.6mg) was statistically superior to Vicodin® for pain relief with a strong trend to superiority at lower doses. A similar pattern was observed in the secondary efficacy measure of time to rescue medication with V1003, once again demonstrating a strong trend to superiority over Vicodin®.
There were no serious adverse events reported in the trial and there were few reports of local irritancy following the nasal delivery of V1003. The most frequent adverse events associated with V1003 were nausea, vomiting, dizziness, sleepiness and were in keeping with its status as a potent opiate analgesic. These events were reported more frequently with V1003 than with Vicodin®, which is a weaker opiate, or placebo.
Vernalis obtained rights to V1003 through its acquisition of Ionix in July 2005 and is developing the product in partnership with Reckitt Benckiser, who manufactures and markets buprenorphine globally. Under the partnership agreement, Reckitt Benckiser is funding all development costs, with Vernalis receiving a series of milestone payments and royalties on commercial sales. Vernalis has retained the option to co-market the product in the U.S. in return for contributing to a proportion of the on-going costs.
Vernalis and Reckitt Benckiser, continue to discuss the most appropriate path forwards for nasal delivery of buprenorphine.
Vernalis has two other pre-clinical programmes based on the proprietary intranasal formulation for the delivery of buprenorphine in partnership with Reckitt Benckiser; V1004 for the treatment of chronic pain and V1005 for the treatment of opiate addiction.