EXPAREL® (liposomal bupivacaine), marketed by Pacira Pharmaceuticals, Inc.; CALDOLOR® (IV ibuprofen), marketed by Cumberland Pharmaceuticals; DSUVIA™ (sublingual sufentanil) marketed by AcelRx Pharmaceuticals, Inc.; and ANJESO™ (IV meloxicam), marketed by Baudax Bio, Inc.; XARACOLL™ (bupivacaine HCL) implant, marketed by Innocoll Holdings plc; and POSIMIR® (bupivacaine solution) marketed by DURECT Corporation. Together with generic versions of IV NSAIDs such as ketorolac and acetaminophen, and generic versions of local anesthetics such as bupivacaine, these non-opioid analgesics are currently used in combination with opioids in the multimodal management of moderate-to-severe acute pain.
We also are aware of a number of products in mid- and late-stage clinical development that are aimed at improving the treatment of moderate-to-severe acute pain and may compete with OLINVYK. AcelRx Pharmaceuticals, Inc. is developing ZALVISO™, a non-invasive PCA device containing sublingual sufentanil, which has received approval in the European Union. Heron Therapeutics Inc. has a proprietary long acting reformulation of bupivacaine in development. Cara Therapeutics Inc. is developing IV and oral dose forms of a peripherally restricted Κ opioid receptor agonist, which has been administered in combination with mu opioids in clinical trials. Avenue Therapeutics, Inc. is developing an IV version of generic opioid tramadol for moderate-to-severe acute pain.
Intellectual property
We wholly own the OLINVYK patent portfolio, including four issued U.S. patents (U.S. Patent Nos. 8,835,488, 9,309,234, 9,642,842, and 9,849,119), which claim, among other things, OLINVYK, compositions comprising OLINVYK, and methods of using OLINVYK. The issued patents are expected to expire no earlier than 2032, subject to any disclaimers or extensions, and any U.S. patent to issue in the future is also expected to expire no earlier than 2032, subject to any disclaimers or extensions. We also have issued patents in Australia, China, Eurasia, Europe, Hong Kong, Israel, Japan, India, South Korea, and New Zealand, which claim among other things, OLINVYK, compositions comprising OLINVYK and methods of making or using OLINVYK. The foreign portfolio also includes an application that has been allowed by the European Patent Office, which claim among other things, OLINVYK, compositions comprising OLINVYK and methods of using OLINVYK. We have patent applications pending in the United States, Europe, Japan, Israel, South Korea, Brazil, Canada, and India. The issued patents and patents that could issue in the future from these allowed or pending applications outside the United States are expected to expire no earlier than 2032, subject to any disclaimers or extensions. Following the FDA approval of OLINVYK, the FDA has added three issued U.S. patents to the Orange Book of Approved Drug Products with Therapeutic Equivalence Evaluations (U.S. Patent Nos. 8,835,488, 9,309,234, 9,642,842). In addition, the Company has filed Patent Term Extension applications with the United States Patent and Trademark Office that could extend the life of one of the patents until 2034. Finally, the FDA has designated OLINVYK as a new chemical entity, or NCE, in the Orange Book and it will therefore receive the exclusivity and protections afforded to NCE’s.
TRV027
TRV027 is a novel beta-arrestin biased ligand that targets the AT1 receptor, inhibiting angiotensin II mediated G protein signaling and activating beta-arrestin signaling. We are developing TRV027 for the treatment of acute lung injury contributing to ARDS and abnormal blood clotting in patients with COVID-19. In a COVID-19 infection, the SARS-coronavirus-2 binds to and removes the ACE2 protein in the lungs and other tissues in the body, causing elevated levels of angiotensin II. This drives overactivation of the AT1 receptor resulting in downstream acute lung injury, which can lead to ARDS, and abnormal blood clotting, which can further lead to pulmonary embolisms and strokes. We believe that TRV027 has the potential to counteract the disproportionate levels of angiotensin II, by competitively binding to and rebalancing AT1 receptor activation. Additionally, we believe its unique mechanism of action preferentially engages the beta-arrestin signaling pathway to promote reparative effects on lung tissue.
Clinical Development
In June 2020, we announced a collaboration with ICL to study TRV027 in a randomized, placebo-controlled study in approximately 60 COVID-19 patients. The primary endpoint of this proof-of-concept study is a coagulation cascade biomarker, which serves as a surrogate for measuring the effect of TRV027 on adverse health outcomes associated with increased mortality in COVID-19 infections. ICL is sponsoring and funding this study, with additional