Depomed agrees to acquire US and Canadian rights to cebranopadol from Grünenthal

Cebranopadol is a novel, first-in-class analgesic in development for the treatment of moderate to severe chronic nociceptive and neuropathic pain and is an important addition to Depomed’s leading portfolio in pain and neurology.

Depomed anticipates advancing cebranopadol into Phase III development for chronic lower back pain (cLBP) and other pain indications by 2017. The deal adds a highly complementary development candidate with a strong efficacy profile, favorable tolerability and low abuse potential with patent protection into the 2030’s to Depomed’s broad commercial platform of pain and neurology marketed products.

Depomed chief medical officer Srinivas Rao said: "Cebranopadol is a truly differentiated molecule with a novel dual mechanism-of-action, functioning as a high-potency agonist of both the mu-opioid and the nociceptin receptors. Cebranopadol’s pharmacology is likely to confer analgesic efficacy equivalent to that of traditional opioids in peripherally-mediated, nociceptive pain conditions, while potentially conferring great efficacy in neuropathic pain and other pain states characterized by more centralized pain.

"Moreover, the product does not appear to impact respiratory function to the degree that traditional mu-opioid receptor agonists do, and the nociceptin receptor pharmacology also appears to substantially mitigate the abuse potential of cebranopadol."

Rao said: "These unique and beneficial properties, along with a strong scientific rationale and a robust clinical package, translate to a strong probability of success – making cebranopadol a great addition to our portfolio. Developmentally, we have a well-defined pathway to follow that we believe has the potential to add tremendous value to both the chronic pain armamentarium and the company."

Depomed president and CEO Jim Schoeneck said: "The acquisition of this novel compound with its unique structure and characteristics fits perfectly with our long-term commitment to expanding our leading pain management portfolio.

"This acquisition builds on Depomed’s leadership in pain, our successful experience in drug development, and further demonstrates our continued ability to do financially creative acquisitions with the goals of improving the lives of patients and increasing shareholder value."

Under the terms of the agreement, Depomed has entered into a settlement agreement with Endo Pharmaceuticals, a subsidiary of Endo International to resolve Depomed’s ongoing patent litigation against Endo for alleged infringement of three of Depomed’s patents by Endo’s OPANA ER product.

As the formulator of OPANA ER, Grünenthal indemnified Endo for certain intellectual property matters, including Depomed’s ongoing patent infringement lawsuit against Endo.

The settlement agreement grants Endo a non-exclusive patent license in the United States, and a covenant not to sue outside the United States, for the currently marketed form of OPANA ER.

In addition, Depomed is providing Grünenthal with a limited covenant not to sue under certain Depomed Acuform drug delivery patents with specific drug substances as well as $25 million in cash. Depomed will also pay Grünenthal royalties on net sales and one-time net sales milestones.

There are no clinical, regulatory or approval milestone payments. The deal is expected to close in the fourth quarter of 2015, following termination or expiration of the waiting period under the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 and completion of other customary closing conditions. The settlement agreement with Endo becomes effective upon the closing under the license agreement.

To date, cebranopadol has been studied in sixteen Phase I, four Phase IIa and three Phase IIb trials in painful diabetic peripheral neuropathy (PDPN), osteoarthritis (OA) and chronic lower back pain as well as a human abuse potential study. In total, cebranopadol has been studied in approximately 2,000 patients worldwide.

In summary, these studies confirm a profile of high potency and efficacy with good tolerability and the potential for a lower abuse profile. Depomed anticipates conducting an End-of-Phase-II meeting with U.S. Food and Drug Administration (FDA) in 2016 and commencing Phase III development by 2017. Cebranopadol has patent protection through at least 2032 with the potential for patent term extension to 2037.

"Cebranopadol is a first-in-class drug candidate due in large part to its unique ability to bind with high affinity to not only classical opioid receptors, but also the nociceptin/ orphanin FQ peptide, or NOP, receptors which may offer improved management of some pain states with decreased side effects. Indeed NOP agonists have been shown to have a broad range of effects, and balanced agonist activity at the NOP and mu receptors may result in an improved safety profile – reduced tolerance and reduced risk of respiratory depression versus mu agonist activity alone," said Frank Porreca, Ph.D. Professor of Pharmacology and Anesthesiology, The University of Arizona College of Medicine at Tucson.

"Arising from Grünenthal, a leader in the development of multifunctional molecules, cebranopadol has the potential to lead the way in novel analgesic therapy."