Opioids: the future and challenging the epidemic

We recently looked at the attempts that have been made to find a long-term solution to the problem of opioid dependence and abuse which has marred the perceived success of this branch of pharmacotherapy.

In 2017, Travena Pharmaceuticals filed Olinvo (oliceridine) with the FDA aimed at moderate to severe acute pain. Trevena asserted that the opioid oliceridine is safer than currently available intravenous opioids, pointing to the drug's mechanism of action as a key differentiating factor, resulting in fewer side-effects. However in 2018 the FDA refused approval, requesting further data.

More successful has been Zilretta (triamcinolone acetonide extended-release injectable suspension) from Flexion Therapeutics. Approved in the US in 2017, the drug is designed to improve the effect of intra-articular corticosteroid treatment for osteoarthritis of the knee. Data from a post-hoc analysis of patients with knee pain presented in 2018 demonstrated that Zilretta provided significant improvement in pain at Week 12 compared with placebo and immediate release triamcinolone acetonide (50% reduction in pain). Those treated also appeared to have sustained response with respect to improvements in pain, stiffness, and physical function. This suggests that Zilretta could offer an alternative to over-the-counter medications, opioids or steroids. Zilretta is also in phase III trials for pain from osteoarthritis of the shoulder and hip. The company has filed a sBLA to secure approval for repeat administration of the drug, to be reviewed on 14 October 2019.

N1539 from Recro Pharma is a new take on meloxicam, a non-steroidal anti-inflammatory drug (NSAID) which is designed to be delivered intravenously. This long-acting, preferential COX-2 inhibitor possesses anti-inflammatory, analgesic, and antipyretic activities and has been marketed by Boehringer since the 1990s as the oral agent, Mobic. However selective COX-2 inhibitors have proved to be problematic with serious cardiovascular side effects and some have been taken off the market. Using a new formulation based on nanotechnology, the IV form provides a faster onset of action, offering a rapid and sustained treatment of acute pain and a potential replacement for opioids. It was filed with the FDA for post-surgical pain and now has a complete response. 

In 2016 the FDA approved Troxyca ER (oxycodone and naltrexone extended release) from Pfizer for moderate to severe pain. The drug has properties to reduce abuse when crushed and when that occurs, the naltrexone is released to counteract the oxycodone.

In 2018 the FDA approved ZTlido, a non-opioid lidocaine medicated plaster from Scilex Pharma/ Sorrento to treat post herpetic neuralgia. The approval was based on a head-to-head study versus Versatis. The product was filed in the EU in November 2017.

In Japan Daiichi Sankyo has secured approval for Tarlige (mirogabalin), the first preferentially selective alpha 2 ligand for peripheral neuropathic pain and diabetic neuropathic pain but the product failed in its trial to treat fibromyalgia.

Awaiting FDA review, on 28 May 2019, is NKTR-181 from Nektar Therapeutics, to treat chronic low back pain. The drug moves from the bloodstream to the central nervous system slowly which should reduce pain relief and avoid the euphoria that attracts addiction. Its abuse potential is similar to a placebo.

Olinvo (oliceridine) from Trevena received a complete response letter from the FDA on 7 November 2018 in relation to its NDA for moderate to severe pain (post-surgical). Trevena asserts that IV oliceridine is safer and has less side effects than earlier IV opioids with a different mechanism of action but the FDA was concerned at the small numbers in the clinical trials and at the QT prolongation effect.

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See the the other 3 parts of the Opioids discussion: Replacement therapies for opioid drugs in pain treatment, Opioids: The war on drugs, Opioids - Over the horizon.