Surmodics, the Eden Prairie-based maker of thin medical devices used inside blood vessels, is reevaluating how to continue human testing of key products that are coated with a drug that the Food and Drug Administration now says may be tied to a greatly elevated risk of death.
A report in the Journal of the American Heart Association found in December that medical devices for the legs containing the widely used anti-inflammation drug paclitaxel were associated with significantly increased chances of death years after treatment in more than a dozen clinical studies. The report caused some hospitals to stop using the devices, and the Basil-3 and Swedepad clinical trials to be suspended indefinitely.
Friday, the U.S. Food and Drug Administration announced that it had analyzed the same clinical trials as the JAHA study and discovered "a potentially concerning" mortality risk. Among 975 patients treated with paclitaxel devices for peripheral artery disease (PAD) in three different randomized trials, there was a 20 percent risk of death at five years with the drug and 13.4 percent chance without it, the FDA said.
The findings are relevant to drug-coated balloons and stents used above the knee in the legs, but not to paclitaxel in cardiac devices or as a chemo agent. The FDA is convening a meeting of its circulatory-device experts later this year to come up with recommendations for how to handle ongoing and future clinical trials involving use of paclitaxel in the legs.
"Because of this concerning safety signal, we believe alternative treatment options should generally be used for most patients while we continue to further evaluate the increased long-term mortality signal and its impact on the overall benefit-risk profile of these devices," the FDA's March 15 letter says of the use of paclitaxel in the femoropopliteal artery in the legs.
Surmodics already has clinical trials going for two devices with paclitaxel. The company's stock price has dropped 12 percent since the FDA's letter on Friday.
"Communication between Surmodics and the FDA is ongoing. At this time we don't have additional information to provide outside the details that were included," in a filing Monday with the U.S. Securities and Exchange Commission, Surmodics spokesman Troy Bergstrom said via e-mail Tuesday.
The filing said Surmodics is trying to get more clarity from the FDA on how its recommendations affect the company's ongoing Transcend clinical trial, which is examining the safety and performance of Surmodics' SurVeil paclitaxel-coated balloon for PAD.
More than 8 million Americans have PAD, which happens when blood vessels in the legs become narrowed or blocked.
One way doctors treat the disease is by inserting a narrow balloon into the artery and precisely inflating it to clear out the blockage. In some cases, doctors also leave a metal mesh tube called a stent in the artery to keep it open.
Paclitaxel is added to the outsides of the balloons and stents because it has been shown to prevent or delay the vessel from re-closing after the procedure.
The FDA said the drug improves blood flow and decreases the chances of the patient needing a follow-up procedure. No definite explanation has been offered for how the drug could be causing late mortality in PAD patients.
Surmodics has long been known as a company that makes other companies' devices or components under contract, and one of its biggest clients is Minnesota's Medtronic. Last year Surmodics unveiled a deal in which Chicago's Abbott Laboratories agreed to pay Surmodics up to $92 million under a global commercialization agreement for rights to the SurVeil drug-coated balloon.
Surmodics has told investors that recent publications on paclitaxel and mortality could affect its ability to continue receiving milestone payments under the Abbott agreement and commercialize the SurVeil balloon. Abbott's agreement with Surmodics includes up to $67 million in milestone payments that have not yet been paid.
The Transcend trial is a significant undertaking for a company that reported $81.3 million in revenue for its most recent fiscal year, which ended Sept. 30, 2018. The six-year pivotal trial is aiming to enroll 446 patients at 78 hospitals around the world, and expected to cost between $32 million and $40 million from inception to completion, securities filings say. The first patient was enrolled in early 2018.
Surmodics' filing on Monday said the FDA may add additional surveillance to trials involving paclitaxel, along with updated patient-consent forms and closer scrutiny of potential drug-related injuries or deaths in the trial.
Major U.S. medical device makers including Medtronic, Boston Scientific, Cook Medical, BD, and Philips sell devices for PAD that contain paclitaxel. Analysts with Barclays Capital estimate that Medtronic's IN.PACT and BD's LUTONIX drug coated balloons for PAD each account for more than $200 million in sales, at above-average profit margins.
Device makers said that their devices still appear safe when examined with more-detailed patient data that is kept in-house, though Medtronic and Cook have both recently corrected paclitaxel papers to clarify the number of deaths in published trial reports.