Forthcoming results of the pivotal phase III trial of Nektar Therapeutics’ mu antagonist naloxegol could place the San Francisco firm in an advantageous position in the opioid-induced constipation market, especially as it will benefit from recent setbacks to two similar drugs.
If the data are positive, as is expected, the drug is set for US approval in 2014 and sales of $32m, rising to $201m in 2018, according to EvaluatePharma’s consensus data. And Nektar does not intend to rest on its laurels: it will then go on to coformulate naloxegol with selected opioids – probably oxycodone or morphine – hoping to create an opioid painkiller that does not cause constipation. The opportunity for such a combination is what is really likely to drive Nektar’s success.
|% of market cap||63%||1%|
|Event type||Phase III trial results|
|Trial IDs||NCT01309841 and NCT01323790|
The chances of naloxegol doing well in the market have increased as two other mu antagonists in development for opioid-induced constipation have recently fallen away. Alkermes abandoned ALKS 37 in May after disappointing phase II results, and the complete response letter the FDA slapped on Relistor in the treatment of patients with chronic, non-cancer pain at the end of July will severely curtail its future sales growth (Progenics and Salix suffer as FDA blocks constipation drug, July 31, 2012).
The other player in this area is Amitiza, a chloride channel activator filed in the US by Sucampo and Takeda. A decision on its approval is expected in May 2013.
Crossing the finish line
Naloxegol is a pegylated version of naloxol, a metabolite of the gold-standard opioid antagonist naloxone. Unlike naloxol and naloxone, naloxegol is unable to enter the brain, meaning it can improve bowel function without interfering with opioid-induced central analgesia. It is being studied in the Kodiac trial programme under the auspices of Nektar’s partner, AstraZeneca. This consists of five trials, of which two randomised, placebo-controlled efficacy studies (NCT01309841 and NCT01323790) are the most crucial.
Analysts at both Roth Capital Partners and Jefferies expect the Kodiac trial to succeed. Jefferies analysts point out that the endpoint of the Kodiac trials is more robust than those used in the trials of Amitiza or oral Relistor, and was requested by the FDA. Kodiac’s endpoint is response; the 12-week study defines a responder as having at least three spontaneous bowel movements per week with an increase of at least one per week over baseline, for at least nine of the 12 weeks and three of the final four weeks.
Furthermore, data from naloxegol’s Phase II trial were positive – it was this that prompted AstraZeneca to snap up rights to the drug in 2009. In that deal, Nektar received $125m up front, with up to $610m in regulatory and commercial milestones and royalties of around 18-25% on sales. Nektar will receive $95m on the acceptance of the filing, with an additional $140m in milestones once the product is approved and launched in the US and the EU. These milestone payments, as well as modest growth of royalty revenue, have led analysts at Roth Capital Partners to expect the company to reach profitability in 2014.
But the two follow-on compounds – the coformulations known as the NKTR-119 programmes – are the real story. Roth analysts put 2018 worldwide sales of naloxegol at $375m and those of NKTR-119 at $230m. However, Roth says that the combinations could eventually have larger potential, with 2025 worldwide sales nearing $1bn. These programmes were also licensed to AstraZeneca as part of the naloxegol deal, with Nektar poised to gain another $770m in milestones for progress with two NKTR-119 combinations, plus royalties.
As more than half of opioid prescriptions are written by general practitioners, AstraZeneca is in an excellent position to penetrate the opioid-induced constipation market with its large, established sales force, Roth analysts say. And with prescriptions for the opioid-naloxegol combinations likely to outstrip those for naloxegol itself, Nektar is in a very sweet position if all goes to plan.
|Summary of Kodiac trials of naloxegol|
|Trial ID||Number of patients||Summary||Start date||Primary completion date|
|NCT01309841||630||12-week, randomized, placebo-controlled
|March 2011||August 2012|
|NCT01323790||630||12-week, randomized, placebo-controlled
|March 2011||September 2012|
|NCT01395524||633||12-week extension study||July 2011||December 2012|
|NCT01384292||340||Efficacy study in patients with
|June 2011||September 2012|
|NCT01336205||1,135||Open-label, randomised, long-term safety study with a usual care comparator arm||April 2011||Janury 2013|
To contact the writer of this story email Elizabeth Cairns in London at firstname.lastname@example.org