Subsys (fentanyl sublingual spray) / Insys Therap - LARVOL DELTA

Comparison of Two Intravenous Drug Combinations for Ambulatory Oral & Maxillofacial Surgery (clinicaltrials.gov) - P1 | N=73 | Completed | Sponsor: Albert Einstein College of Medicine

New P1 trial • Anesthesia

Intrathecal Hydromorphone vs Intrathecal Morphine to Treat Post Cesarean Pain in Patients With Opioid Use Disorder Taking Buprenorphine (clinicaltrials.gov) - P4 | N=46 | Not yet recruiting | Sponsor: University of North Carolina, Chapel Hill

New P4 trial • Pain • Substance Abuse

Opioids for pain. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Addiction (Opioid and Alcohol) • Pain

Comparison table: Some oral/transdermal opioid analgesics. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Pain

"ICYMI, FDA strengthened the REMS program for transmucosal immediate-release fentanyl products to help improve the ability to monitor for adverse events and ensure safe use of these medicines" (@FDA_Drug_Info)

Adverse events

Fentanyl Sublingual Spray for Exercise-Induced Breakthrough Dyspnea (clinicaltrials.gov) - P2/3; N=50; Active, not recruiting; Sponsor: M.D. Anderson Cancer Center; N=30 ➔ 50

Enrollment change • Oncology

Prophylactic Fentanyl Sublingual Spray for Episodic Exertional Dyspnea in Cancer Patients: A Pilot Double-Blind Randomized Controlled Trial. (PubMed, J Pain Symptom Manage) - "Prophylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High dose FSS should be tested in confirmatory trials."

Clinical • Journal • Oncology • Pain

Assessment of Potentially Inappropriate Prescribing of Opioid Analgesics Requiring Prior Opioid Tolerance. (PubMed, JAMA Netw Open) - "Less than half of use episodes (73 117 episodes [47.7%]) involved patients with evidence in claims data of opioid tolerance prior to initiating therapy with an OTO medication, including 31 392 of 101 676 episodes (30.9%) involving transdermal fentanyl, 1561 of 2440 episodes (64.0%) involving transmucosal fentanyl, 36 596 of 43 559 episodes (84.0%) involving extended-release oxycodone, and 3568 of 5710 episodes (62.5%) involving extended-release hydromorphone...Data from EHRs did not contribute substantial additional evidence of opioid tolerance beyond the data found in prescription claims. Future research is needed to understand the clinical rationale behind these observed prescribing patterns and to quantify the risk of harm to patients associated with potentially inappropriate prescribing."

Journal • Addiction (Opioid and Alcohol) • Pain

Sublingual Fentanyl for the Management of Breakthrough Pain (clinicaltrials.gov) - P2; N=6; Terminated; Sponsor: M.D. Anderson Cancer Center; Trial completion date: Feb 2021 ➔ Nov 2019; Active, not recruiting ➔ Terminated

Clinical • Trial completion date • Trial termination • Oncology • Pain

Fentanyl Sublingual Spray for Exercise-Induced Breakthrough Dyspnea (clinicaltrials.gov) - P2/3; N=30; Active, not recruiting; Sponsor: M.D. Anderson Cancer Center; Trial completion date: Jan 2021 ➔ Dec 2022; Trial primary completion date: Jan 2020 ➔ Dec 2021

Trial completion date • Trial primary completion date • Oncology

The reasons and timing of the oral transmucosal fentanyl administration in Japan (ESMO Asia 2017) - "...Median dose of fentanyl patch was 25mcg/hr (range 12.5-250mcg/hr). 90 patients (81%) had difficulties in the administration of oral medicine, which was the main reason of Abstral administration...ROO was administered for the patients who cannot take the oral medicine while it is supposed to be administered to those who want to relieve BTcP fast. In addition, it was administered after aggressive treatment in many patients. The study results represented the short prognosis of these patients."

Retrospective data • Oncology

Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications (Future Med Chem) - "In this review, we outline the structural and corresponding synthetic strategies that have been used to understand the structure-biological activity relationship in fentanyl-related compounds and derivatives and their biological activity profiles."

Review • Pain

Management of breakthrough pain in children with cancer (J Pain Res) - "The most common and effective strategy seems to be multimodal analgesia that includes an immediate-release opioid (eg, morphine, fentanyl, hydromorphone, or diamorphine) administered intravenously by a patient-controlled analgesia pump...Intranasal fentanyl (or hydromorphone) may be an alternative, but no pediatric data have been published yet for commercially available fentanyl transmucosal application systems (ie, sublingual tablets/spray, buccal lozenge/tablet/film, and nasal spray), and these products cannot yet be recommended for use with children with cancer and breakthrough pain."

Review • Pain

Pomerantz law firm has filed a class action against Insys Therapeutics, Inc. and certain officers -- INSY (Globenewswire) - "Pomerantz Grossman Hufford Dahlstrom & Gross LLP has filed a class action lawsuit against Insys Therapeutics, Inc...The Complaint alleges...Defendants made false and/or misleading statements concerning, and/or failed to disclose, among other things that...the Company engaged in illegal and/or unethical marketing of Subsys...the Company was exposed to potential fines and other disciplinary actions as a result of its Subsys marketing practices; and...as a result, the Company's financial statements were materially false and misleading at all relevant times."

Corporate lawsuit • Pain

Insys Therapeutics announces listing of U.S. patents covering Subsys use and formulation in FDA's Orange Book (Marketwire) - "Insys Therapeutics...announced today that the U.S. Food and Drug Administration (FDA) has listed U.S. Patent...in its Approved Drug Products with Therapeutic Equivalence Evaluations, or Orange Book. Both of these patents cover SUBSYS brand fentanyl sold by Insys and will expire no sooner than 2027."

Anticipated patent expiry • Pain

Fentanyl sublingual spray improved pain management in cancer patients (Healio) - P=NA, N=226; "Pain management scores on the Treatment Satisfaction Questionnaire for Medication improved after titration. From baseline to post-titration, a mean improvement of 26.1 points was recorded for effectiveness (standard deviation [SD]=20.9)."

Clinical data • Pain

Fentanyl Sublingual Spray in Opioid Naive Participants (clinicaltrials.gov) - P1; N=96; Completed; Sponsor: INSYS Therapeutics Inc; Recruiting ➔ Completed

Trial completion • Biosimilar

Insys Therapeutics (INSY) provides prelim. Q3 Subsys revenue; notes drop in prescriptions (Streetinsider.com) - "Insys Therapeutics...announced that its preliminary estimated revenues from Subsys (fentanyl sublingual spray) for the third quarter of 2016 will be in the range of $54 million to $55 million."

Anticipated sales • Demo Pain • Pain

Insys Therapeutics' (INSY) CEO Mike Babich on Q1 2014 results - Earnings call transcript (SeekingAlpha) - "In Q1 2014, we announced that the FDA approved an IND studying Subsys to evaluate in a preprocedural setting. The study enrolls opioid naïve and tolerant patients undergoing interventional procedures....We plan to initiate additional study this year for Subsys in areas that can further expand the market for this product."

Anticipated new trial • Pain

Insys Therapeutics reports second quarter 2013 results (Marketwire) - "Subsys generated $18.5 million in net revenue during the second quarter of 2013, up 90.8% quarter-over-quarter from $9.7 million in the first quarter of 2013."

Sales • Pain

Insys announces details of product development pipeline (Marketwire) - "The Company also intends to initiate Phase IV studies of SUBSYS® (fentanyl sublingual spray)...to explore its potential utility in the following additional indications and applications...Pain procedures in office setting...Pediatric use."

Anticipated new indication • Anticipated new P4 trial • Pain

Bernstein Liebhard LLP announces that a class action has been filed against Insys Therapeutics, Inc. (PRNewswire) - "The Complaint alleges...Defendants made false and/or misleading statements concerning, and/or failed to disclose, among other things that...the Company engaged in illegal and/or unethical marketing of Subsys...the Company was exposed to potential fines and other disciplinary actions as a result of its Subsys marketing practices; and...as a result, the Company's financial statements were materially false and misleading at all relevant times."

Corporate lawsuit • Pain

Insys announces NDA PDUFA date for fentanyl SL spray (Businesswire) - FDA has provided anticipated PDUFA goal date of Jan 4, 2012 for review of NDA for fentanyl SL spray.

Anticipated PDUFA date • Pain

Fentanyl Sublingual Spray in Opioid Naive Participants (clinicaltrials.gov) - P1; N=96; Not yet recruiting; Sponsor: INSYS Therapeutics Inc

New P1 trial • Biosimilar

Pharmacokinetics and Safety of Fentanyl Sublingual Spray and Intravenous Fentanyl Citrate in Adult Opioid-Naive Healthy Volunteers: A Randomized, Open-Label, Single Ascending Dose Study (PAINWeek 2016) - "A single dose of fentanyl sublingual spray of up to 400 mcg may be safely administered without the need for supplemental oxygenation in an opioid-naive healthy population in an appropriately monitored and equipped setting. Supported by INSYS Therapeutics, Inc."

P1 data • PK/PD data • Biosimilar • Demo Pain • Oncology • Pain