Opinion ID: 4110875
Heading Depth: 3
Heading Rank: 1

Heading: Onyx

Text: Onyx is an artificial liquid material developed by MTI to treat malformed blood vessels in the brain. In plain terms, it is injected into blood vessels near the brain, and then forms a mass blocking the flow of blood to facilitate subsequent surgery. In the early 2000s, MTI licensed the Onyx molecule to a company named Enteric. Enteric used the molecule to develop another medical device, Enteryx, which went to market first, after gaining Food and Drug Administration (FDA) approval in April 2003 for the treatment of gastroesophageal reflux disease. A series of adverse events involving Enteryx followed, prompting a patient safety alert in October 2004, and culminating in a complete recall of the device in September 2005. It was during this timeframe--between Enteryx's approval and recall--that MTI sought approval for Onyx. The FDA's regulations require a premarket approval (PMA) process for medical devices like Onyx. See 21 C.F.R. § 814.1(c). During that process, the device manufacturer supplies the FDA with extensive information regarding the device--including its design, manufacturing, packing, labeling, and testing--to satisfy the agency that the device is safe and effective. Id. § 814.20. A sufficiently complete application proceeds to substantive review. Id. § 814.42(a). That review is performed by FDA personnel and, at the FDA's election as in this instance, by an - 4 - advisory panel of outside experts. Id. § 814.44(a). The panel holds a public meeting to review the PMA before making a recommendation to the FDA. Id. § 814.44(b). The FDA then considers the PMA application, together with any advisory panel report and recommendation, before issuing a decision on approval. Id. § 814.44(c). MTI's PMA application identified a narrow indication for Onyx: use in the treatment of brain arteriovenous malformations ('BAVM's'), when embolization is indicated to minimize blood loss to reduce the BAVM size prior to surgery. While seeking approval, MTI emphasized the narrow scope of the indication as well as the rigorous nature of the training program required for physicians using Onyx. According to the testimony of MTI's Vice President before the FDA advisory panel, that training program would include an instructional session, a hands-on workshop, a case review, and observations. According to another MTI witness, any physician who completed this training would receive the assistance of an experienced proctor the first time he or she used Onyx. The advisory panel members placed great weight on these training requirements, describing them as critically important and a very big component of getting [Onyx] into safe use. The panel ultimately recommended approval of Onyx. However, several of its members explained that it was a cautious approval, and others warned that they would advise the FDA to - 5 - rescind approval if MTI disregarded their suggestions for carefully monitoring Onyx cases. The FDA adopted the panel's recommendation, granting approval to Onyx in July 2005. The Onyx label authorized by the FDA restricted the device's use to physicians with neurointerventional training and a thorough knowledge of the pathology to be treated, angiographic techniques, and superselective embolization. It stated, Contact your Micro Therapeutics Inc. sales representative for information on training courses. Enter D'Agostino, a sales representative who worked at ev3 from January 2005 until his termination in January 2010. After ev3 acquired MTI in 2006, D'Agostino became familiar with the manner in which the defendants promoted and sold Onyx. He says that he observed physician trainings that lasted as little as four hours and proctored surgeries that involved off-label procedures. He also alleges that the defendants instituted a Site Certification Process whereby they certified and sold Onyx to any site where a single neurosurgeon who had completed their training enjoyed privileges. As a result, he says that Onyx fell into the hands of physicians at those sites with inadequate training or no training at all. Additionally, the defendants encouraged offlabel marketing by setting sales quotas for their representatives that anticipated such sales, educating their sales force on - 6 - peripheral applications, and providing off-label training to physicians during all-expenses-paid retreats. All in all, it became clear, alleges D'Agostino, that the defendants never intended to honor the commitments that MTI had made to the FDA.