Remoxy ER (extended-release oxycodone capsules CII) / Cassava, Durect - LARVOL DELTA

Sustained Risk Reduction of Severe Clinical Outcomes Following Misuse/Abuse of XTAMPZA ER as Compared to Other Prescription Opioids (PAINWeek 2023) - " Using NPDS data (01January2019 - 31December2022), frequency of misuse/abuse exposures and clinical outcomes were compared between XTAMPZA ER, other ER oxycodone (oral solid dosage forms of ER oxycodone excluding XTAMPZA ER), other ER opioids for analgesia (oral solid dosage forms of ER formulations of hydrocodone, oxymorphone, hydromorphone, morphine), and IR oxycodone (oral solid dosage forms)... This study suggests that XTAMPZA ER (an ADF ER oxycodone medication) may have a reduced risk of misuse/abuse than opioid medications compared in this study. Exposures to XTAMPZA ER reported to US poison centers were less likely to involve misuse/abuse than the opioid medications included in the other three study groups and no XTAMPZA ER exposure reported use by a nonoral route of administration, the routes associated with the highest risk for severe clinical outcomes. Life-threatening events and death were significantly less likely to occur with exposure to XTAMPZA ER than for..."

Clinical • Clinical data • Addiction (Opioid and Alcohol) • CNS Disorders • Pain

Population Pharmacokinetics and Pharmacogenomics of Oral Oxycodone in Pediatric Surgical Patients (clinicaltrials.gov) - P4; N=68; Recruiting; Sponsor: Boston Children's Hospital; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: May 2020 ➔ May 2021

Biomarker • Clinical • Trial completion date • Trial primary completion date • Pediatrics

PedPK: Population Pharmacokinetics and Pharmacogenomics of Oral Oxycodone in Thai Pediatric Surgical Patients (clinicaltrials.gov) - P4; N=20; Active, not recruiting; Sponsor: Mahidol University; Recruiting ➔ Active, not recruiting; Trial completion date: Apr 2019 ➔ Dec 2020; Trial primary completion date: Mar 2019 ➔ Aug 2020

Biomarker • Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Anesthesia • Pediatrics

IntelliPharmaceutics International Inc: Ladenburg - IPCI: Focusing on Analyst Day July 12th for Rexista update; 2Q11 results in line with expectations (Ladenburg, Thalmann & Co) - Analysts continue to expect FDA approval of Remoxy to be delayed by at least 18 months

Financial analyst: Regulatory • Pain

Pain Therapeutics, Durect shares soar on Pfizer's Remoxy comments (Reuters) - "Shares of Pain Therapeutics Inc (PTIE.O) and Durect Corp (DRRX.O) rose more than 40 percent after partner Pfizer Inc (PFE.N) said it is in talks with U.S. health regulators to find a way forward on the companies' painkiller, Remoxy...On a post-earnings call on Tuesday, Pfizer said it had a "productive meeting" with the regulator in March...Read declined to specify what the agency wants, or how Pfizer will satisfy the agency's requirements -- including whether new studies or new analyses of completed studies have been requested."

FDA event • Stock price • Pain

Durect Corporation announces fourth quarter 2012 financial results and update of programs (PRNewswire) - "'Communications with Pfizer indicate that they intend to meet with the FDA as planned in late March to discuss their proposed resubmission plan for REMOXY®'...We have multiple programs that may potentially be licensed over the next 12-18 months. These include POSIDUR, TRANSDUR-Sufentanil, ELADUR,..."

Anticipated FDA event • Anticipated licensing / partnership • Pain

Durect Corporation announces first quarter 2013 financial results and update of programs (PRNewswire) - "We note the recent additional patent issuance extending coverage of REMOXY in the U.S. to at least 2031...DURECT has two transdermal products...TRANSDUR®-Sufentanil...ELADUR®...We are in discussions with potential partners regarding licensing development and commercialization rights to these two transdermal programs for which we hold worldwide rights."

Anticipated licensing / partnership • Anticipated patent expiry • Pain

Effects of Oral or Intranasal Oxycodone Alone or inCombination With Naltrexone on End-Tidal Carbon Dioxide (ASA 2016) - " These results indicate that naltrexone, released from crushed ALO-02 pellets, when administered via either the oral or nasal routes, may attenuate the effects of oxycodone on EtCO2 in recreational opioid users. Studies using additional measures of respiratory function are required to further evaluate the effect of naltrexone on oxycodone-induced respiratory depression and its clinical significance."

Clinical • Biosimilar • CNS Disorders • Demo Pain • Depression • Oncology • Pain

PedPK: Population Pharmacokinetics and Pharmacogenomics of Oral Oxycodone in Thai Pediatric Surgical Patients (clinicaltrials.gov) - P4; N=20; Not yet recruiting; Sponsor: Mahidol University; Trial completion date: Nov 2019 ➔ Apr 2020; Initiation date: Nov 2017 ➔ Apr 2018; Trial primary completion date: Oct 2018 ➔ Mar 2019

Trial completion date • Trial initiation date • Trial primary completion date • Biosimilar

"The FDA has nixed approval of Remoxy ER for severe pain. https://t.co/7gW9x6Nrqd" (@Medscape)

FDA event • CNS Disorders • Pain

Pain Therapeutics reports Pfizer elects to continue development of Remoxy (Pain Therapeutics Press Release) - "Pain Therapeutics, Inc. (Nasdaq:PTIE) today reported Pfizer Inc. (NYSE:PFE) has informed us that, having achieved technical milestones related to manufacturing, they will continue the development program for REMOXY® (oxycodone) Extended-Release Capsules CII....The complete response submission is not expected to occur prior to mid-2015....Pfizer has returned to us all rights with respect to abuse-resistant formulations of hydrocodone, hydromorphone and oxymorphone....We are now free to develop and commercialize these assets on our own or with a licensee of our choice, and may do so without notice or approval from Pfizer."

Anticipated FDA event • Pipeline update • Pain

Predictive factors for nausea or vomiting in patients with cancer who receive oral oxycodone for the first time: Is prophylactic medication for prevention of opioid-induced nausea or vomiting necessary? (J Palliat Med) - P=NA, N=280; "This analysis identified gender (male) (odds ratio [OR]=0.429), lung cancer (OR=2.049), and steroid use (OR=0.417) were significant factors for the occurrence of opioid-induced nausea. For vomiting, gender (male) (OR=0.4) and use of dopamine D2 blockers (OR=2.778) were significant factors."

Adverse events • Pain

Indication of adequate transdermal fentanyl dose in opioid switching from oral oxycodone in patients with cancer (Am J Hosp Palliat Care) - P=NA, N=122; "Regression analysis for the data from 122 patients suggested that the typical conversion ratio was 95:1; however, this ratio was significantly reduced in patients taking a daily oral morphine-equivalent dose of <45 mg/d and in patients with poor pain control to 52:1 and 64:1, respectively."

Clinical data • Pain

Pain Therapeutics reports FY 2014 financial results (GlobeNewswire) - " 'Our current priority is to work cooperatively with Pfizer on an orderly transfer of REMOXY', said Remi Barbier, Chairman, President & CEO. 'We are excited by the prospect of regaining worldwide rights to REMOXY. In 2015 we plan to keenly focus on REMOXY, our main asset. A secondary goal for 2015 is to develop FENROCK, our proprietary abuse-deterrent pain patch...' "

Pipeline update • Pain

Pain Therapeutics announces update on drug portfolio (GlobeNewswire) - "Pain Therapeutics...today announced an update regarding its portfolio of drug candidates....Expected milestones include a clear path to the FDA for re-filing the REMOXY NDA, announcement of proof-of-concept results for an abuse deterrent transdermal pain patch...We plan to conduct certain non-clinical activities prior to re-filing the REMOXY NDA. This includes in vitro work that was initiated but never completed by REMOXY's previous sponsor due to the timing of their decision to return REMOXY....We plan to refile the REMOXY NDA with FDA in Q1 2016."

Anticipated NDA • Anticipated preclinical • Pain

FDA rejects Pain Therapeutics' Remoxy ER marketing application; shares plummet 67% premarket (SeekingAlpha) - "Thinly traded micro cap Pain Therapeutics...craters 67% premarket on increased volume in response to its announcement that it received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA) seeking approval of abuse-deterrent REMOXY ER (oxycodone capsules CII)."

FDA event • Stock price • Demo Pain • Pain

Risk/reward remains positive for Durect (SeekingAlpha) - “We see Remoxy as having potential peak sales in the $1.5 billion range…We model Remoxy approval in 2016 at Pfizer, with sales eclipsing $1.5 billion by 2020.”

Anticipated NDA • Sales projection • Pain

Corporate Presentation (Durect) - "Met Primary Endpoint: Reduction in pain scores over 3 months compared to placebo (p<0.01); Met Secondary Endpoints: Quality of Analgesia (p<0.01), Global Assessment (p<0.01)"

P3 data • Pain

Durect Pharma: Corporate Presentation (Durect) - Anticipated patent coverage in US for pain through 2031; Anticipated patent coverage in EU for pain through 2023; Anticipated eligible patent term extension for pain through 2033/2034

Anticipated patent expiry • Pain

Durect: Q4 & FY 2012 Results (Durect) - Anticipated US patent expiries for two families for pain in 2015 and 2025; Anticipated EU patent expiries for two families for pain in 2016 and 2023

Anticipated patent expiry • Pain

Pain Therapeutics: Annual Report 2012 (Pain Therapeutics) - Anticipated patent expiry in US for pain in 2025 or after; Anticipated patent expiry for two granted patents in EU for pain in 2016 and 2026

Anticipated patent expiry • Pain

FDA complete response letter received for Remoxy (Globenewswire) - Based on its review, the FDA has determined that NDA for Remoxy is not approved; The FDA's CRL raised concerns related to, among other matters, the chemistry, manufacturing, and controls section of the NDA for Remoxy; Certain drug lots showed inconsistent release performance during in vitro testing; In opinion of Pain Therapeutics, potential regulatory approval of Remoxy in US unlikely to occur in less than one year, and could be delayed significantly longer than a year

Pain

FDA Complete Response Letter Received for Remoxy (Pfizer) - Pfizer is working to evaluate the issues described in the Complete Response Letter and plans to have further discussions with FDA around them

Pain

Durect announces update on Remoxy (Durect) - "DURECT...announced that Pfizer has provided an update on Remoxy as part of their Form 10-Q filing...We met with the FDA in March 2013 to discuss our plan to address the June 2011 "complete response" letter. We received written guidance from the FDA in May regarding required next steps, including additional clinical studies, to address the letter. Based on this guidance, we are considering our options with respect to Remoxy. If we elect to continue development of Remoxy, we would not expect to submit a response to the "complete response" letter before mid-2015."

Anticipated FDA event • Pipeline update • Pain

Healthcare stocks falling near close; Pain therapeutics soars after Pfizer restarts trial of new pain-killer (Nasdaq) - "Pain Therapeutics Inc. ( PTIE ) is up nearly 43%...following reports Pfizer ( PFE ) is close to restarting Phase I testing of Remoxy...The upcoming trial will begin later this month and examine the effects of food on oxycodone pharmacokinetics following 40-milligram doses of the drug...Pfizer ( PFE ) is down about 1.1% at $28.48 a share in late trade...Another company with Remoxy in its pipeline is Durect Corp ( DRRX ). Its shares are up nearly 23% at $1.29 each."

New P1 trial • Stock price • Pain