Naldemedine

Unassigned

New Medicines

Rizmoic Opioid-induced constipation in adults

Information

Rizmoic
New molecular entity
Shionogi
Shionogi

Development and Regulatory status

Launched
Launched
Launched
December 2019
Dec 19Launched in the UK. Price is £41.72 for a pack of 28. Sandoz is the distributor but Shionogi is the MAH [18].
Oct 19Will be available to prescribe for palliative care and hospital/private use first. The product itself should be available to order from wholesalers for hospital use in the next month. Price 1x28 200mg tablets =£41.72. Company does not anticipate potential availability for NHS prescription use (FP10) until 2020 [17].
Feb 19Approved in the EU [14].
Dec 18Recommended for EU approval by CHMP - the full indication is "the treatment of opioid-induced constipation (OIC) in adult patients who have previously been treated with a laxative” [13].
Oct 17Launched in the US for the treatment of OIC in adult patients with chronic non-cancer pain, following its approval in March 2017 [11].
Mar 17Filed in EU, according to EMA monthly list compiled 3/4/17 [9]
Mar 17FDA has approved neldemedine for the submitted indication. The drug will be jointly commercialised together with Purdue Pharma, and is expected to be available mid-summer 2017. The companies have petitioned the US Drug Enforcement Administration to have the drug removed from its current listing as a Schedule II controlled substance in the US (it is listed because it is structurally related to naltrexone) [8].
Jun 16The FDA has accepted the NDA for naldemedine with a target action date of 23rd March 2017; also submitted for licensing in Japan, but no indication of any imminent intention to submit in the EU [7].
Mar 16Shionogi have submitted their New Drug Application to the US FDA, for treatment of opioid-induced constipation in patients with chronic non-cancer pain [6].
Feb 16Latest PIII results, presented at the American Academy of Pain Medicine, mark the third PIII success for naldemedine, & Shionogi plans to file for FDA approval in 1H 2016 [5].

Category

Peripherally-selective μ-opioid receptor antagonist
Opioid-induced constipation is a side effect that affects nearly all patients taking opioid treatment and will persist unless treated. The prevalence of opioid-induced constipation is not known. However, in England in 2010 there were over 17 million prescriptions for opioid items. In 2010-11 there were 57,506 hospital admissions due to constipation in England, and in 2011, there were 57 deaths registered in England and Wales due to constipation.
Opioid-induced constipation in adults
Oral

Further information

Yes
To be confirmed

Trial or other data

Mar 18Results of Compose III (NCT01965652) published in PAIN. RCT (n=623) found fewer treatment emergent side effects with naldemedine vs placebo after 52 weeks (68.4% vs 72.1%, difference -3.6%, 95% CI -8.7 to -1.5). Iimprovements in overall constipation-related symptoms was observed with naldemedine vs placebo at all time points (P≤ 0.0001) [12].
Oct 17Results of 2-week RCT (COMPOSE-4) and 12-week extension study (COMPOSE-5) published in Journal of Clinical Oncology. COMPOSE-4 (n=193) reports proportion of spontaneous bowel movement (SBM) responders (defined as ≥ 3 SBMs/week and an increase of ≥ 1 SBM/week from baseline) was significantly greater with naldemedine than with placebo (71.1% v 34.4%; P<0.0001) [10].
Feb 16Shionogi announces naldemedine met its primary endpoint by increasing the frequency of bowel movements for 47.9% of patients in at least 9 of the study´s 12 weeks vs. placebo (a 34.6% difference) [5].
Aug 15Once-daily 0.2mg naldemedine met primary endpoint in PIII study (COMPOSE II, NCT01993940, n=553) for treatment Of opioid-induced constipation in pts with chronic non-cancer pain. Naldemedine improved the frequency of spontaneous bowel movement (SBM) vs. placebo over 12 weeks. Naldemedine was generally well-tolerated. The most common side effects were gastrointestinal disorders [4].
Mar 15Shionogi report COMPOSE I (NCT01965158) met its primary and secondary endpoint. Naldemedine 0.2mg od improved the frequency of spontaneous bowel movement (SBM) compared with placebo over 12 weeks with a statistical significance [3].
Nov 13NCT01993940 is a randomized, double-blind, placebo-controlled PIII study of naldemedine (0.2 mg once daily) in the treatment of opioid-induced constipation in 540 subjects with non-malignant chronic pain receiving opioid therapy. The primary efficacy endpoint is the proportion of responders who have a spontaneous bowel movement. The study starts Nov 13 and is due to complete Feb 16 [1].
Oct 13Compose III (NCT01965652) a phase III trial will study the long-term safety of naldemedine daily vs. placebo for the treatment of opioid-induced constipation in subjects with non-malignant chronic pain receiving opioid therapy. The primary outcome is number of major adverse cardiac events over a 1 year period. The study aims to enrol 1500 patients and is due to complete in May 16 [2].
Aug 13A phase III trial (NCT01965158; COMPOSE 1) to assess the safety and efficacy of naldemedine (0.2mg once daily) for the treatment of opioid-induced constipation in patients with non-malignant chronic pain is underway. Patients will receive naldemedine or placebo once daily for 12 weeks. The primary efficacy outcome is proportion of responders who have a spontaneous bowel movement. The study is due to complete in July 15 [2].

Evidence based evaluations