Anamorelin

Published

dm+d

Unassigned

New Medicines

AdlumizAnorexia, cachexia or unintended weight loss in patients with non-small cell lung cancer

Information

Adlumiz
New molecular entity
Helsinn
Helsinn

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Apr 21Helsinn, through its partner Ono Phamaceuticals, launches Adlumiz (anamorelin) in Japan for the treatment of cancer cachexia in malignant non-small cell lung cancer, gastric cancer, pancreatic cancer and colorectal cancer. Ono has exclusive rights to develop and commercialise the product in Japan, South Korea and Taiwan. Helsinn retains full rights in the rest of the world. The two PIII SCALA trials (ANAM-17-20 and ANAM-17-21) are ongoing and Helsinn plans to provide an update on them and hopes to bring the treatment to more and more patients globally [21].
Nov 19PIII (globally) in company pipeline for anorexia-cachexia in NSCLC [18].
Sep 17Second EU negative opinion [15].
Jun 17Helsinn Birex has requested a re-examination of the CHMP opinion. Upon receipt of the grounds of the request, the CHMP will re-examine its opinion and issue a final recommendation [14].
May 17EU negative opinion. The CHMP concluded that the studies show a marginal effect of Adlumiz on lean body mass and no proven effect on hand grip strength or patients’ quality of life. In addition, following an inspection at clinical study sites, CHMP considered that the safety data on the medicine had not been recorded adequately. This meant that a thorough evaluation of potential risks with Adlumiz was not possible [13].
Nov 15Filed in EU via centralised procedure [11].
Jul 14Under the terms of the agreement with Chugai, Helsinn will retain all development activities (CMC, preclinical and clinical) and supply of the drug for commercial use [7].
Mar 14Enrolment in the ROMANA 1 and 2 trials was completed in October and September of 2013, respectively. Results for these trials are expected in 2015. [6]
Mar 13ROMANA 1 and II expected to complete July 2013 [4].
Dec 11First patient enrols in ROMANA 3 trial (NCT01395914) in the US [3]

Category

Ghrelin receptor agonist
Cancer cachexia is present in approximately 50% of cancer patients during treatment, and nearly 100% of treated cancer patients at death. It accounts for at least 20% of deaths in neoplastic patients. Cancer cachexia impairs quality of life and response to therapy, increasing morbidity and mortality of cancer patients. [2]
Anorexia, cachexia or unintended weight loss in patients with non-small cell lung cancer
Oral

Further information

Yes

Trial or other data

Jun 21PIII trials (NCT03743064; ANAM-17-21) and (NCT03743051; ANAM-17-20) are still recruiting and now due to complete collecting primary outcome data in Dec 21 [23].
Dec 20PIII trials (NCT03743064; ANAM-17-21) and (NCT03743051; ANAM-17-20) are due to complete collecting primary outcome data in Sep 21 [22].
Sep 20PIII study (NCT03743064) is also recruiting and running to plan with regards collection of data [20].
Sep 20PIII study to evaluate the efficacy and safety of anamorelin HCl is recruting (NCT03743051). Approximately 316 patients with advanced NSCLC with cachexia will be randomized 1:1 to anamorelin HCl 100 mg or placebo, taken orally once daily (QD) for a total of 24 weeks. Patients will be instructed to take the study drug at least 1 hour before their first meal of the day. the study started in Dec 18, and is due to complete collection of primary outcome data in Dec 20 [20].
Feb 20PIII study (NCT03743064) is still recruiting; no change to planned timescales [19].
Oct 19PIII study (NCT03743064) is recruiting; collection of primary outcome data is due to complete Dec 20 [17].
Mar 19First patient dosed in the new global PIII trial (NCT03743064) to evaluate anamorelin for the treatment of weight loss and anorexia in patients with advanced NSCLC with cachexia [16].
Feb 16Final results from ROMANA I and ROMANA II trials published in Lancet Oncology; patients receiving anamorelin increased lean body mass compared to placebo (median difference 1.46 and 1.63 kg respectively at week 12), however hand-grip strength was not significantly improved [12].
Dec 14Results of an integrated analysis of two phase II, randomised, placebo-controlled, double-blind trials have been published in the Lancet. The pooled data show that over 12 weeks, anamorelin increased lean body mass by 1.89kg (95% CI 0•84 to 2•95) compared with a decrease of 0•20 kg (−1•23 to 0•83) for patients in the placebo group (difference 2•09 kg [0•94–3•25]; p=0•0006). [10]
Oct 14Presentation of results from pivotal 12 week ROMANA 1 PIII study (NCT01387269) in which pts with unresectable Stage III/IV NSCLC and cachexia were randomised (2:1) to 100 mg anamorelin or placebo orally + continued chemotherapy if indicated. Anamorelin significantly increased lean body mass (LBM) vs. placebo (median change from baseline of 1.10 kg [95% CI 0.76; 1.42] vs. - 0.44 kg [95% CI -0.88; 0.20]). The most frequent drug-related adverse events of anamorelin included hyperglycemia (incidence 5.3%) and nausea (3.8%). [9]
Oct 14Data from two PIII studies in patients with advanced NSCLC showed statistically significant improvement vs. placebo in LBM with anamorelin [8].
Nov 13Helsinn has granted Chugai Pharma exclusive commercialization rights to anamorelin, for Germany, France, Benelux, UK and Ireland [5].
Mar 13ROMANA I = NCT01387269; ROMANA II = NCT01387282
Aug 11Ghrelin is a hormone that is predominantly produced in the stomach. Administration of ghrelin rapidly stimulates appetite, which may lead to increased food intake and body weight, as well as other physiologic activities including increasing lean body mass and stimulating gastric emptying. [1]
Aug 11Two pivotal PIII randomised, double-blind, placebo-controlled trials to be run in parallel, ROMANA-1 and ROMANA-2., each enrolling up to 477 patients. In addition, patients will have the option of continuing treatment in a 12-week safety extension study called ROMANA-3. Primary efficacy endpoints of ROMANA-1 and 2 include a measure of difference in the change in lean body mass and muscle strength in patients with advanced NSCLC-associated weight loss. Pharmacokinetic and additional safety measures will also be assessed. [1]

Evidence based evaluations