The third time held no charm for Intarcia Therapeutics, which saw its long road through the FDA potentially forced down another detour.
The company’s history already holds two rejections from the agency for its miniaturized implant, which is designed to slowly release a Type 2 diabetes medication over the course of six months. Now, a committee of outside advisers has told the FDA it should ask Intarcia for additional data on the implant’s safety.
Intarcia was once a biotech unicorn, raising north of $1 billion in venture capital cash by pitching a device about the size of a matchstick that potentially could do away with twice-daily or once-weekly injections of the GLP-1 agonist exenatide, the active ingredient used in the branded drugs Byetta and Bydureon.
Over several years, the 2007 Fierce 15 company posted several massive fundraisings, with individual hauls amounting to $210 million, $215 million and $206 million, among other rounds. But Intarcia’s fortunes dwindled after it received FDA rejection letters in 2017 and 2020, pushing the company to lay off staff and cut back its R&D plans. Today, the company currently operates as a business unit of i2o Therapeutics, following a recent acquisition.
The agency had made its reluctance known once again in late 2021: After denying three of Intarcia’s formal dispute resolution requests—as well as a request for an advisory committee meeting—the FDA published a public notice outlining how its reviewers intended to reject the company’s application once again, if it continued to move forward.
But Intarcia finally got its long-sought advisory committee meeting this week. Ultimately, the panel unanimously voted against recommending approval of the implant, dubbed ITCA 650, based on the currently available data.
Panel members expressed concerns over safety signals seen in previous studies and pointed to the possibility of acute kidney injuries and cardiovascular side effects that may be driven by uneven delivery of the drug over time.
ITCA 650 features a titanium implant known as a DUROS device, which is placed under the skin. It contains an osmotic pump and a piston that slowly pushes out a special, viscous exenatide formulation from a reservoir. In its presentation to the FDA, the company said the device includes a fail-safe that prevents it from delivering the drug all at once as a bolus dose. DUROS implants had previously been approved for use with Bayer’s palliative prostate cancer drug Viadur, but the product was discontinued in 2007.
In its 2020 complete response letter rejecting the company’s application, the FDA urged Intarcia to redesign the product to make the drug-release rates more reliable and to then conduct new clinical trials to test it.
Previous phase 3 clinical trials showed about a 0.7 percentage point reduction in A1C measurements, beating a placebo, according to the FDA. The agency is not required to follow the panel’s recommendations when it makes a final decision.
Meanwhile, ITCA 650 was picked up by i2o Therapeutics in late August. In addition to gaining Intarcia’s assets, i2o also scooped up Intarcia's president and CEO Kurt Graves, who replaced i2o’s former chief, Ravi Srinivasan. Graves had also formerly served as executive chairman of i2o’s board.