Xtampza ER (oxycodone) / Collegium Pharma - LARVOL DELTA

Col003 attenuates sepsis-associated coagulation dysfunction in mice in association with reduced platelet activation and NET formation. (PubMed, Thromb Res) - "These findings suggest that HSP47-associated responses are involved in sepsis-associated coagulation dysfunction and are linked to platelet activation and NET formation. Early Col003 intervention attenuated CLP-induced pathological changes, supporting HSP47-associated pathways as potential targets for further investigation in sepsis-associated coagulopathy. Further studies are needed to determine whether delayed Col003 administration remains effective after sepsis has been established."

Journal • Preclinical • Cardiovascular • Hematological Disorders • Infectious Disease • Septic Shock • Venous Thromboembolism • MYD88 • SERPINH1 • TLR2

HSP47 inhibitor Col003 attenuates thromboinflammation after cerebral ischemia-reperfusion by suppressing GPVI-mediated CD84 shedding in platelets. (PubMed, Mol Immunol) - "The HSP47 inhibitor Col003 suppresses GPVI-mediated shedding of CD84 from platelets, alleviates platelet-mediated inflammatory responses and cerebral microthrombus formation, and reduces the infiltration of CD4 + T cells and other immune cells in the cerebral infarct region. These results indicate that targeting HSP47 produces functional effects similar to those achieved by inhibiting the GPVI pathway, thereby providing a novel potential target and therapeutic strategy for ischemic stroke."

Journal • Cardiovascular • CNS Disorders • Hematological Disorders • Inflammation • Ischemic stroke • Reperfusion Injury • Thrombosis • CD31 • IL1B • PECAM1 • PTPRC • SERPINH1 • TNFA

HSP47 inhibitor Col003 inhibits glial scar formation and improves neurological function in ischemic stroke in rats. (PubMed, Brain Res Bull) - "Our findings demonstrated that Col003 inhibited JAK2/STAT3 phosphorylation in OGD/R-induced astrocytes. The HSP47 inhibitor Col003 might suppress astrocyte proliferation, migration, and glial scar formation through the JAK2/STAT3 pathway following ischemic stroke, which suggests a novel therapeutic strategy for the chronic phase of ischemic stroke."

Journal • Preclinical • Cardiovascular • Ischemic stroke • GFAP • SERPINH1

HSP47 inhibitor Col003 may attenuates neurological impairment in chronic ischemic stroke rats by inhibiting LCN2. (PubMed, Neurol Res) - "Col003 decreased JAK2/STAT3 phosphorylation in ischemic brain tissue. In rats with chronic ischemic stroke, Col03 may lessen the size of the cerebral infarction and neurological impairments by blocking LCN2 through the JAK2/STAT3 signaling pathway."

Journal • Preclinical • Cardiovascular • CNS Disorders • Ischemic stroke • LCN2 • SERPINH1

A collagenous extracellular matrix regulates germline gene expression in the sea star embryo. (PubMed, Sci Rep) - "Here we used β-aminopropionitrile (BAPN), a well-known inhibitor of lysyl oxidase (LOX; an enzyme important for cross-linking mature collagen), a morpholino antisense oligonucleotide to LOX2A, and Col003, an inhibitor of collagen processing to test for a role of the collagen-based ECM with cells that form the germ line...Our results show that disruption of the ECM dysregulates germline gene expression and normal gut morphogenesis during specific development stages. This paradigm adds to a growing list of mechanisms in how primordial germ cells use the ECM in an inductive mode."

Journal • ATF3 • BMP2 • STAR

Motivations, perceived risk, and tampering of XTAMPZA ER and abuse-deterrent opioid drugs. (PubMed, PLoS One) - "Tampering with XTAMPZA® ER was uncommon compared to other drugs but more common as a proportion among those who used XTAMPZA® ER. This is, potentially because those using XTAMPZA® ER had other markers of severe, problematic drug use."

Journal • Pain

Late Breaking Abstract - Intratracheal administration of Col003 loaded in ginseng-derived extracellular vesicles for therapy of idiopathic pulmonary fibrosis (ERS 2025) - "In vivo, C57BL/6 mice were divided into six groups: blank, bleomycin (BLM), BLM+@GDNP, BLM+Col003@GDNP, BLM+PFD@GDNP, and BLM+PFD. Col003@GDNP effectively alleviated pulmonary fibrosis by downregulating HSP47 and inhibiting fibroblast activation, demonstrating potential as an effective IPF treatment."

Late-breaking abstract • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • SERPINH1 • TGFB1

Opioid Abuse Deterrent Formulations: Evaluation of Nonmedical Use of Other Prescription Opioid Substances and Routes of Administration in Adults Evaluated for Substance Use Treatment with the Addiction Severity Index-Multimedia Version (ASI-MV®) (PAINWeek 2025) - "Three groups were created: assessments reporting XTAMPZA ER (ADF) NMU, assessments reporting other oxycodone ER (all oxycodone ER products except Xtampza ER - ADFs) NMU, and assessments reporting oxycodone Immediate Release (IR) (non-ADFs) NMU. Of the 341,851 ASI-MV assessments completed from 01 July 2016 through 31 December 2023, 141 assessments reported past 30-day XTAMPZA ER NMU; 4,935 reported other oxycodone ER NMU; and 20,394 reported oxycodone IR NMU. 138 of the 141 (97.9%) XTAMPZA ER NMU assessments also reported other prescription opioid NMU; 4,733 of the 4,935 (95.9%) other oxycodone ER NMU assessments also reported other prescription opioid NMU, and 16,517 of the 20,394 (81.0%) oxycodone IR NMU assessments also reported other prescription opioid NMU. Nonoral routes of administration (ROAs) were indicated in 22.0% of assessments reporting XTAMPZA ER NMU including snorting only (9.9%); oral ROAs and snorting (5.0%); injecting only (2.1%); oral ROAs, snorting,..."

Clinical • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry

Trends in XTAMPZA ER and other oxycodone misuse and abuse during COVID-19: A mosaic approach. (PubMed, J Opioid Manag) - "Overall, there is no evidence that oxycodone misuse and abuse worsened during COVID-19 in these populations, and XTAMPZA ER was consistently lower than other oxycodone products. Low rates and improving trends in oxycodone misuse and abuse may signify an ongoing reduction in prescription opioid contributions to the opioid crisis."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Substance Abuse

Postmarketing Research for Opioid Abuse-Deterrent Formulations: A Narrative Review. (PubMed, J Pain Res) - "Currently, 4 opioid formulations carry the ADF designation: XTAMPZA® ER (oxycodone), OXYCONTIN® (oxycodone hydrochloride), HYSINGLA™ ER (hydrocodone bitartrate), and ROXYBOND™ (oxycodone hydrochloride). Of note, XTAMPZA ER has shown sustained lower levels of nonoral abuse or misuse compared with other ADFs, despite a substantial increase in dispensed prescriptions since its launch in 2016. Additional postmarketing research is needed, especially for HYSINGLA ER and ROXYBOND."

Journal • P4 data • Review • Pain

Integrated analysis of tumor and adjacent non-tumor proteomic data reveals SERPINH1 as a recurrence biomarker and drug target in hepatocellular carcinoma. (PubMed, Int J Biol Sci) - "This study highlights the significant importance of NATs in recurrence prediction and postoperative management, proposing a recurrence management strategy that focuses on both tumors and NATs. SERPINH1 emerges as a valuable biomarker and drug target for addressing postoperative recurrence in HCC."

Biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • SERPINH1

Opioid-related clinical outcomes and associated healthcare costs following abuse/misuse of oxycodone formulations: A HEOR analysis from real-world data. (PubMed, J Opioid Manag) - "This study is the first of its kind to synthesize clinical outcomes with opioid-related healthcare costs, suggesting that even when Xtampza ER is abused/misused, the rates of major effect/death, ED visits, and hospital admissions were significantly lower than those for other oxycodone-containing medications, resulting in relatively low downstream opioid-related healthcare costs."

Clinical • Clinical data • HEOR • Journal • Observational data • Real-world • Real-world evidence

Nonmedical Use and Route of Administration of XTAMPZA® ER versus Other Oxycodone Medications (Extended- and Immediate-Release) in Adults Evaluated for Substance Use with the Addiction Severity Index-Multimedia Version (ASI-MV®) (PAINWeek 2024) - "Of the 341,851 assessments completed, 67,855 reported past 30-day NMU of any prescription opioid medication. Of those, 141 (0.2%) reported past 30-day NMU of XTAMPZA ER, 4,935 (7.3%) reported past 30-day NMU of other ER oxycodone, and 20,394 (30.1%) reported past 30-day NMU of an IR oxycodone product (groups are not mutually exclusive as NMU of more than one product can be reported in any given assessment). Study groups were similar in gender distribution (49-53% male) and age (greatest proportion 25-34 years).Quarterly NMU drug utilization-adjusted rates of XTAMPZA ER ranged from 0.17 (95% CI 0.02-1.17) to 5.32 (95% CI 2.77-10.22) mentions per 1m dosage units dispensed, however only three quarterly rates were greater than 2.0 mentions per 1m dosage units dispensed."

Clinical • Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry • Substance Abuse

Curbing Opioid Abuse: Real-World Evidence of Abuse-Deterrent Formulations (PAINWeek 2024) - "Background: For patients who experience refractory chronic pain, opioid analgesics remain an important component of multimodal treatment; however, opioid misuse and abuse pose a serious and challenging public health problem.1 Prescription opioids were associated with approximately 45 deaths per day in 2021, totaling more than 17,000 deaths.2 Opioid abuse-deterrent formulations (ADFs) were developed as a component of a multifactorial strategy to combat the opioid epidemic.3-4 To date, there are 4 opioids (1 immediate release [IR] and 3 extended release [ER]) with US Food and Drug Administration (FDA)—approved abuse-deterrence label claims, including ROXYBONDTM IR (oxycodone), reformulated OXYCONTIN ER® (oxycodone), HYSINGLA ER® (hydrocodone), and XTAMPZA ER® (oxycodone). XTAMPZA ER had significantly lower rates of nonmedical use including nonoral nonmedical use than OXYCONTIN (P< 0.001) and the non-ADF oxycodone IR (P< 0.001) products in individuals..."

Clinical • HEOR • Real-world • Real-world evidence • Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry • Substance Abuse

Collegium Announces Eight Poster Presentations at PAINWeek Conference 2024 (GlobeNewswire) - "Collegium Pharmaceutical, Inc...today announced that eight poster presentations highlighting data regarding its diversified pain portfolio will be presented at PAINWeek Conference 2024, being held in Las Vegas, NV, from September 3–6, 2024."

Clinical data • Back Pain • CNS Disorders • Pain

Collegium Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "Grew Belbuca total prescriptions 2.1% year-over-year and 1.4% quarter-over-quarter in the quarter ended June 30, 2024. Belbuca net revenue was a record $52.2 million, up 21% year-over-year. Xtampza ER net revenue was $44.6 million, up 8% year-over-year. Achieved Xtampza ER gross-to-net of 56.2% in the quarter ended June 30, 2024. Xtampza ER gross-to-net is expected to be in the range of 55% to 57% for the full-year 2024, an improvement from the previous guided range of 56 to 58%."

Sales • Back Pain • CNS Disorders • Pain

Review of Opioid Abuse-Deterrent Formulations: Impact and Barriers to Access. (PubMed, J Pain Res) - "Xtampza ER utilizes DETERx technology, which allows it to retain ER characteristics when chewed or crushed, making it the only ER opioid without a boxed warning against these types of manipulation. OxyContin was also developed as an ADF but uses RESISTEC technology, making the tablet hard to crush and viscous in aqueous solutions...However, similar studies comparing abuse-related effectiveness and health care costs for ADF opioids are warranted if clinicians are expected to utilize these potentially safer opioid formulations. These studies would support further education surrounding the benefits and utilization of ADFs and manipulation potential of different ADFs."

Journal • Review • Pain

Targeting the HSP47-collagen axis inhibits brain metastasis by reversing M2 microglial polarization and restoring anti-tumor immunity. (PubMed, Cell Rep Med) - "Col003, an inhibitor disrupting HSP47-collagen association restores an anti-tumor immunity and enhances the efficacy of anti-PD-L1 immunotherapy in BrM-bearing mice. Our study supports that HSP47 is a critical determinant of M2 microglial polarization and immunosuppression and that blocking the HSP47-collagen axis represents a promising therapeutic strategy against brain metastatic tumors."

Journal • Brain Cancer • Oncology • Solid Tumor • CD8 • SERPINH1

Collegium Reports First Quarter 2024 Financial Results (GlobeNewswire) - "Collegium Pharmaceutical, Inc...today reported its financial results for the quarter ended March 31, 2024, and provided a corporate update....Grew Belbuca total prescriptions 4.2% in the quarter ended March 31, 2024, compared to the prior year quarter. Belbuca net revenue was a record $50.7 million, up 15% year-over-year. Achieved Xtampza ER gross-to-net of 53.6% in the quarter ended March 31, 2024. Xtampza ER gross-to-net is expected to be in the range of 56% to 58% for the full-year 2024."

Commercial • Back Pain • CNS Disorders • Pain

Oxycodone Extended-Release Capsule Utilization for Pain Management in a Cancer Palliative Care Clinic: A Retrospective Review. (PubMed, J Pain Palliat Care Pharmacother) - "Xtampza ER™, an oxycodone extended-release capsule (OERC), was the first long-acting opioid to feature abuse-deterrent properties and various routes of administration without pharmacokinetic alterations...There were no significant variables identified to influence pain scores either statistically or clinically. Further studies are needed to determine the long-term efficacy and safety in cancer palliative-care patients."

Journal • Retrospective data • Review • Oncology • Pain • Palliative care

Differences in severity of poison centers exposures involving XTAMPZA ER versus other opioid analgesics. (PubMed, Pain Manag) - "Xtampza ER was compared with other ADF opioids, non-ADF extended-release opioids, single-entity oxycodone immediate-release, unspecified oxycodone and unspecified morphine. Results & No Xtampza ER exposures involved unintended routes of administration. Xtampza ER exposures were less likely to be abuse, misuse or suspected suicidal, and medical outcomes were less severe than comparators."

Journal • Pain

Use of Causal Framework to Evaluate Effect of Abuse Deterrent Properties of XTAMPZA ER on Opioid Tampering in a Post-Market Setting (PAINWeek 2023) - "Our analysis provides direct evidence in accordance with FDA guidance for labelling of an ADF product, XTAMPZA ER, and utilized a causal framework. The analysis assessed whether there was a concurrent reduction in abuse behaviors by tampering associated with use of XTAMPZA ER in a post-approval setting. Tampering of oxycodone products by individuals using XTAMPZA ER was rare and similar to individuals using other oxycodone products."

P4 data • CNS Disorders • Pain

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

Real-world impact of abuse-deterrent formulation of XTAMPZA ER in the context of behaviors around tampering with XTAMPZA® ER and other opioid products (PAINWeek 2023) - "Purpose/Objectives: This study compares the rate of tampering with XTAMPZA® ER to the rate of tampering with immediate-release (IR) single entity (SE) oxycodone, other ER oxycodone opioids, and ER oxymorphone in order to assess the efficacy of ADF technology in a real-world setting. Tampering with XTAMPZA® ER was reported less frequently than most comparator products in an OUD treatment center population, and NMU of this product was reported less frequently than other products in the general population. These findings highlight the impact of ADF technology in discouraging non-oral use among individuals with OUD. As such, there is a need for more research into the uptake of ADF opioids and identification of related barriers."

Clinical • Real-world • Real-world evidence • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • Substance Abuse

Healthcare Costs Associated with Rates of Prescription Opioid Misuse/Abuse (PAINWeek 2023) - "This study found that intentional misuse/abuse exposures to XTAMPZA ER (an ADF ER oxycodone medication) resulted in significantly fewer hospital admissions and lower hospital admission costs than other ER oxycodone, other ER opioids for analgesia, and IR oxycodone. Exposures to XTAMPZA ER were 40-318 times less likely to result in a hospital admission and therefore the estimated healthcare cost was orders of magnitude less than exposures to the other three study groups. Consistent with previous reports, incorporating ADF opioid medications may help reduce the community based public health risks of opioid misuse/abuse and associated healthcare costs."

HEOR • Addiction (Opioid and Alcohol) • CNS Disorders