Opioid-free Pain relief for Enhanced Recovery After Spine fixation surgery

Project Information

OPERAS

Grant agreement ID: 190122961

DOI

10.3030/190122961

Project closed

EC signature date 14 July 2023

Start date 1 April 2023

End date 31 March 2026

Funded under

• The European Innovation Council (EIC)

Total cost

€ 5 687 678,50

EU contribution

€ 2 500 000,00

Coordinated by

SENTRYX BV
Netherlands

Periodic Reporting for period 2 - OPERAS (Opioid-free Pain relief for Enhanced Recovery After Spine fixation surgery)

Reporting period: 2024-04-01 to 2026-03-31

Summary of the context and overall objectives of the project

Spine fixation surgery is among the most painful surgical procedures performed today. Patients routinely receive high-dose opioids to manage postoperative pain, despite well-documented side effects including nausea, sedation, confusion, and respiratory depression, and a 18% risk of opioid dependence after surgery. Meanwhile, up to 80% of patients still experience insufficient pain relief in the first few days, which is linked to the development of chronic postsurgical pain, which currently affects one in five patients. Unlike hip and knee replacement, where hospital stay has halved over the past two decades, spine fixation patients still spend more than four days in hospital on average. No approved implantable or sustained-release local analgesic product existed for this indication.

BR-003 (Bupi-Ring) is a ring-shaped hydrogel designed to be co-implanted with spine fixation screws during surgery. It delivers an approved and well-established local pain blocker called bupivacaine directly at the surgical site for more than 72 hours, which is nine times longer than conventional injections. As such, it provides ultra-sustained non-opioid local pain relief without altering the surgical workflow, after which the hydrogel biodegrades in the body. The underlying technology is a viscoelastic, ultra-pure modified gelatin developed entirely in-house, protected by a broad patent portfolio with granted patents in the EU, US, and China.

The OPERAS project, supported by the EIC Accelerator with blended finance of €2.5 million grant and €13 million equity, was designed to advance BR-003 from preclinical proof-of-concept to clinical and commercial readiness for late-stage development. The project ran for 36 months (April 2023 – March 2026) and was structured around three objectives: conducting a Phase Ib clinical trial to demonstrate first-in-human safety; developing a comprehensive market access strategy; and managing the project including IP portfolio maintenance and regulatory preparation.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The central activity of OPERAS was a Phase Ib clinical trial enrolling 11 patients across two study sites in the Netherlands and Switzerland, organised in two ascending dose cohorts and overseen by an independent Data Safety Monitoring Board (DSMB). The primary safety endpoint was that the peak plasma bupivacaine concentration (Cmax) remained below the accepted systemic safety threshold of 2,000 ng/mL. This endpoint was met in all 11 patients, with a mean Cmax of 149 ng/mL, 13 times below the safety limit. Bupivacaine remained measurable in the blood plasma for two weeks, confirming ultra-sustained local drug availability well beyond the critical first 72 hours of recovery. Exploratory efficacy outcomes showed 42% lower opioid consumption and 49% lower back pain scores compared to an observational cohort of 41 patients treated with standard care. No BR-003-related serious adverse events were observed up to one year after surgery. The safety results were independently validated by the DSMB and published in a peer-reviewed journal.

In addition, the protocol for an adaptive Phase II/III single pivotal trial was completed, and EMA scientific advice endorsing the proposed clinical development strategy was obtained in February 2026. Regulatory interactions with the Dutch medicines authority and the US FDA confirmed that a single European pivotal trial is acceptable to both authorities. A comprehensive market access strategy was completed in January 2026, covering health economic modelling, market research, key opinion leader engagement, and a commercialisation approach. All 14 deliverables and all 3 milestones of the project were achieved.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

OPERAS advanced BR-003 from TRL 6 (technology demonstrated in relevant environment, following GLP preclinical studies in sheep) to TRL 7 (system prototype demonstrated in operational environment), as confirmed by the DSMB validation of the Phase Ib results. The peer-reviewed publication in the Journal of Regional Anesthesia and Pain Management (BMJ Group) is the first published clinical study of an implantable sustained-release local anaesthetic for spine surgery, and the first human pharmacokinetic characterisation of this drug delivery approach. The patent portfolio at project completion comprises nine families covering the co-implantation application, the viscoelastic hydrogel technology, and the manufacturing processes, with three new PCT applications filed during the project period.

The target market comprises approximately 1.2 million spine fixation procedures per year in Europe and the United States, growing at a CAGR of 5.7%. Activity-based cost analyses indicate that opioid-related complications and extended hospital stay add approximately €2,300 in direct hospital costs per procedure. At 40% peak market penetration, the serviceable obtainable market exceeds €1 billion. With the Phase Ib evidence base in place and EMA scientific advice obtained, the company is well-positioned to initiate the adaptive Phase II/III trial, which will form the basis for market approval applications in the EU and US.