Daiichi Sankyo Release: MOVANTIK (naloxegol) Safety Analyses Of Opioid-Induced Constipation Patients 65 And Older With Chronic Non-Cancer Pain

WILMINGTON, Del.--(BUSINESS WIRE)--Further analysis of the Phase III KODIAC-04, KODIAC-05 and KODIAC-08 studies presented today at Digestive Disease Week (DDW) 2015 in Washington, D.C. showed that MOVANTIK^TM (naloxegol) had a similar incidence of adverse events (AEs) among elderly patients as compared to placebo or usual care. The study evaluated the effects of daily oral administration of MOVANTIK 12.5 mg or 25 mg vs placebo among outpatients 65 years and older with opioid-induced constipation (OIC) and chronic non-cancer pain.

The incidence of AEs reported among patients taking MOVANTIK was similar to those taking placebo or usual care. Safety results among this subset were generally consistent with those seen in the overall patient populations from phase 3 studies.

Specific findings from the sub-analyses of patients aged 65 years and older included:

• In the KODIAC-04 and KODIAC-05 (n=147/1,331) studies:
  • The incidence of AEs was: naloxegol 12.5 mg, 50.0% (22/44); naloxegol 25 mg, 56.6% (30/53); placebo, 62.0% (31/50)
  • The most common gastrointestinal (GI) AEs in older patients taking naloxegol were diarrhea, vomiting, nausea, and abdominal pain
  • No GI events were adjudicated as related to bowel perforation
  • The incidence of serious AEs (SAEs: placebo, 4.0% (2/50); naloxegol 12.5 mg, 6.8% (3/44); naloxegol 25 mg, 3.8% (2/53) and discontinuations due to AEs (placebo, 8.0% (4/50); naloxegol 12.5 mg, 6.8% (3/44); naloxegol 25 mg, 7.5% (4/53) were comparable among treatment groups in the 12-week pool
  • One patient (aged 73 years, receiving naloxegol 12.5 mg) had an adjudicated cardiovascular event (acute myocardial infarction) that was judged unrelated to treatment
• In the KODIAC-08 (n=76/721) study:
  • The incidence of AEs was: naloxegol 25 mg, 86.7% (39/45); usual care, 83.9% (26/31)
  • The most common GI AEs in older patients taking naloxegol were diarrhea, vomiting, nausea, and abdominal pain
  • No GI events were adjudicated as related to bowel perforation
  • The incidence of serious AEs were 16.1% (5/31) for usual care and 15.6% (7/45) for naloxegol 25 mg. Discontinuations due to AEs with naloxegol were 13.3% (6/45). Patients receiving usual care did not receive investigational medication and therefore discontinuations for AEs were not assessed

The most common adverse reactions with MOVANTIK as compared to placebo in clinical trials were abdominal pain (21% vs. 7%), diarrhea (9% vs. 5%), nausea (8% vs 5%), flatulence (6% vs 3%), vomiting (5% vs 4%), headache (4% vs. 3%), and hyperhidrosis (3% vs. <1%).

MOVANTIK is the first once-daily oral peripherally-acting mu-opioid receptor antagonist (PAMORA) medication for the treatment of OIC in adult patients with chronic, non-cancer pain. When administered at recommended dose levels, MOVANTIK decreases the constipating effect of opioids by blocking opioids from binding to mu-receptors in the bowel. And because of its design, at recommended doses, the CNS penetration of naloxegol is expected to be negligible, limiting potential interference with centrally mediated opioid analgesia.

IMPORTANT SAFETY INFORMATION ABOUT MOVANTIK

MOVANTIK™ (naloxegol) is contraindicated in:

• Patients with known or suspected gastrointestinal (GI) obstruction and patients at increased risk of recurrent obstruction, due to the potential for GI perforation
• Patients receiving strong CYP3A4 inhibitors (eg, clarithromycin, ketoconazole) because these medications can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms
• Patients with a known serious or severe hypersensitivity reaction to MOVANTIK or any of its excipients
• Cases of GI perforation have been reported with the use of another peripherally acting opioid antagonist in patients with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the GI tract. Monitor for severe, persistent, or worsening abdominal pain; discontinue if this symptom develops
• Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning, occurred in patients treated with MOVANTIK. Patients receiving methadone as therapy for their pain condition were observed in the clinical trials to have a higher frequency of GI adverse reactions that may have been related to opioid withdrawal than patients receiving other opioids. Patients with disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal or reduced analgesia. These patients (eg, multiple sclerosis, recent brain injury, Alzheimer’s disease, and uncontrolled epilepsy) were not enrolled in the clinical studies. Take into account the overall risk-benefit profile when using MOVANTIK in such patients. Monitor for symptoms of opioid withdrawal when using MOVANTIK in such patients
• Avoid concomitant use of moderate CYP3A4 inhibitors (eg, diltiazem, erythromycin, verapamil) because they may increase the risk of adverse reactions. Use of strong CYP3A4 inducers (eg, rifampin, carbamazepine, St. John’s Wort) is not recommended because they may decrease the efficacy of MOVANTIK. Avoid concomitant use of MOVANTIK with another opioid antagonist due to the increased risk of opioid withdrawal
• The use of MOVANTIK during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood-brain barrier. MOVANTIK should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Due to the potential for serious adverse reactions, including opioid withdrawal, in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother
• The most common adverse reactions with MOVANTIK as compared to placebo in clinical trials were: abdominal pain (21% vs. 7%), diarrhea (9% vs. 5%), nausea (8% vs 5%), flatulence (6% vs 3%), vomiting (5% vs 4%), headache (4% vs. 3%), and hyperhidrosis (3% vs. <1%)

Please see full US Prescribing Information
http://www.azpicentral.com/movantik/movantik.pdf

NOTES TO EDITORS

About the KODIAC Clinical Program

The FDA approval of MOVANTIK was based on data from the KODIAC clinical program, which is comprised of four studies: KODIAC-4, -5, -7 and -8. KODIAC-4 and -5 were both placebo controlled, double-blind, 12 week studies assessing safety and efficacy, while KODIAC-7 was a 12 week safety extension to KODIAC-4, and KODIAC-8 was a 52 week long-term, open-label, safety study.

About MOVANTIK^™ (naloxegol)

MOVANTIK™ (naloxegol) Tablets is the first FDA approved once-daily oral peripherally-acting mu-opioid receptor antagonist (PAMORA) specifically designed for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. In the Phase III clinical studies, MOVANTIK was administered as a once-daily tablet and was designed to block the binding of opioids to opioid receptors in tissues such as the gastrointestinal (GI) tract.

MOVANTIK is part of the exclusive worldwide license agreement announced on September 21, 2009 between AstraZeneca and Nektar Therapeutics. MOVANTIK was developed using Nektar’s oral small molecule polymer conjugate technology.

On March 19, 2015, AstraZeneca announced a co-commercialization agreement with Daiichi Sankyo, Inc. for MOVANTIK in the US, in line with the Company’s strategy of delivering value through its own development and commercial capabilities as well as through external collaboration.

About Daiichi Sankyo, Inc.

Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical products to address the diversified, unmet medical needs of patients in both mature and emerging markets. While maintaining its portfolio of marketed pharmaceuticals for hypertension, dyslipidemia and bacterial infections used by patients around the world, the Group has also launched treatments for thrombotic disorders and is building new product franchises. Furthermore, Daiichi Sankyo research and development is focused on bringing forth novel therapies in oncology and cardiovascular-metabolic diseases, including biologics. The Daiichi Sankyo Group has created a ‘Hybrid Business Model’ to respond to market and customer diversity and optimize growth opportunities across the value chain. For more information, please visit: www.daiichisankyo.com. Daiichi Sankyo, Inc., headquartered in Parsippany, New Jersey, is a member of the Daiichi Sankyo Group. For more information on Daiichi Sankyo, Inc., please visit www.dsi.com.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit www.astrazeneca-us.com.

3120303 Last Updated 5/15