Tell me again why we couldn't possibly get FDA approval after failing significance on primary endpoints?



https://www.medtechdive.com/news/mainstay-wins-fda-approval-for-chronic-back-pain-device-following-mixed-cli/580327/

Mainstay wins FDA approval for chronic back pain device following mixed clinical data

By

Nick Paul Taylor

Published

June 23, 2020

Dive Brief:

• FDA has approved Mainstay Medical’s ReActiv8 neurostimulation system to treat a form of intractable chronic low back pain, 19 months after ReActiv8 failed a clinical trial designed to generate data to open up the U.S. market.

• Having persuaded FDA the overall dataset supports approval, the Dublin-based medical device maker plans to start selling the device in the U.S. in 2021. Mainstay and FDA disclosed the premarket approval Monday.

• Boston Scientific and Medtronic already sell neurostimulation devices to treat chronic back pain, but Mainstay is targeting a different group of patients.

Dive Insight:

Mainstay's history can be split between before and after it published results from the U.S. trial of the ReActiv8 implant. In the run up to the 2018 data readout, Mainstay went public, received investment from organizations including Medtronic and secured a CE mark. Australia’s regulator delayed a filing for approval when it requested additional clinical data, but Mainstay looked set to quickly resolve its concerns with data from the U.S. trial.

Upon the release of data from the U.S. trial, shares in Mainstay plummeted 45% and never bounced back. The stock drop reflected the downgrading of expectations in light of data that showed ReActiv8 was no better than a sham control at driving 30% or greater improvements in low back pain.

The comparable response rates in the treatment and control cohorts of the trial 120 days after the procedure caused the study to miss its primary endpoint. However, ReActiv8 did beat the control when patients who increased their use of pain medication for reasons other than back pain were stripped from the analysis.

Mainstay pinned the primary endpoint failure on a higher-than-expected initial response in the sham control group, pointing to trends after the 120-day cutoff to make its case. Equipped with that data and positive secondary endpoint analyses, including evidence of a reduction in opioid use, Mainstay filed for FDA approval last year.

The approval allows Mainstay to target a subpopulation of patients whose chronic low back pain has a mechanical cause related to functional spine instability. Spinal cord stimulation, the dominant form of neurostimulation today, has failed to generate compelling data in such nociceptive pain patients, or those with common pain from a physical injury.

That creates a potential market opportunity for ReActiv8, which works by stimulating motor fibers rather than sensory fibers, and may therefore be better suited to the treatment of nociceptive pain. Today, individuals with nociceptive pain are treated with physical therapy and drugs, including opioids.

With regulatory OKs to sell ReActiv8 in the U.S. and Europe, Mainstay contends it has an addressable market of more than 2 million patients. The specific population suitable for the ReActiv8 implant has chronic low back pain that persists despite conservative treatments, an impaired multifidus muscle, and is ineligible for spine surgery.

Mainstay is now “refining its commercial launch plans for ReActiv8 in the U.S.” based on the PMA and evaluating the money it will need to build out its sales team and start selling the device in the U.S. in the first half of next year. In the past, Mainstay could have used its dual stock listings in Paris and Dublin to raise cash, but the company delisted from the exchanges earlier this month in response to “poor demand for shares and thin volumes leading to large volatility in price.”