Pain Management

Narcotics is an attractive opportunity for pain management :

• An $8 billion market: Narcotics such as opioids represent one third of the total pain market, with a growth rate expected to increase significantly over the next decade. Two of the top-five products within the total pain market are narcotics with sales above $1b for each.

• A higher probability of success: The average success rate for phase 1-to-market drug development is 9% for all drugs, however it is 17% for pain relief drugs.

• A shorter development time: For post-operative pain, the completion of clinical phases 1 and 2 is significantly shorter than most other therapeutic areas.

The main drawbacks of existing narcotics are undesirable effects, more specifically constipation and tolerance. Constipation has a direct impact on health costs for post-operative recovery and can be life-threatening when opioids are used to reduce chronic pain. Tolerance means that repeated intakes result in higher doses to get an equivalent effect, eventually reaching toxic doses.

Neorphys scientists discover and develop the Neorphines, a novel family of drug candidates which are more potent than morphine while reducing these restricting side effects, in a growing number of therapeutic areas, such as acute pain, chronic pain, orthopaedic pain and dental pain.

Opioid induced constipation is seen as the most important drawback of opioids by patients, physicians and regulatory agencies. It has a direct impact on health costs in postoperative care and on chronic pain management. Recently, several major deals between big pharma and biotech companies have confirmed the critical importance of this need. They propose various combinations of an opioid agonist to reduce pain with an opioid antagonist to reduce constipation. 

Neorphys has designed and patented NEO1509, a drug candidate which exhibit both benefits in only one molecule, showing a higher analgesic effect than morphine together with a full recovery of normal transit during analgesia. Moreover, it shows no respiratory depression and no addiction in animal models. 

As a first application, NEO1509 is targeting postoperative pain. It is an opioid featuring a long lasting effect, both by oral and i.v. routes of administration. It is presently in advanced regulatory preclinical development. It should enter clinical phase 1 in 2011 and phase 2 in 2012. NEO1528 is an orally-available form of NEO1509, with animal proof of concept studies for various chronic pain models. Therefore, it will benefit from a significant synergy with the regulatory development of NEO1509. Only a limited number of additional regulatory packages will have to be performed.

Neorphines are derived from natural metabolites of morphine and are spread over proprietary chemical series, so as to maximise synergies in the discovery effort and to increase its odds of success (EP 2081944, WO 2008043962, filed 12 October 2006, R.71(3) EPC Notification February 2, 2010).

The main improvements of Neorphines compared to other opioids including morphine are:

• Long lasting effect (8 to 10 times longer than morphine)

• Recovery of normal gastro-intestinal transit while under analgesia

• No sign of respiratory depression at doses close to the MTD

• No addictive effect in place preference assays

• Low risk of tolerance

• Activity demonstrated by several routes of administration including oral, iv, sc

• Safety window higher than 100 by oral administration

• High solubility and stability in water