Medical Device Daily Associate
Ariad Pharmaceuticals (Cambridge, Massachusetts) has entered into non-exclusive agreements with cardiovascular device maker Medinol (Tel Aviv, Israel) to develop and commercialize stents and other medical devices to deliver Ariad's mTOR inhibitor, AP23573, to prevent reblockage of injured vessels following stent-assisted angioplasty.
Under the agreement, Ariad is eligible to receive license fees and regulatory, clinical and commercial milestones of up to $39.25 million, if two products are developed, plus royalties on worldwide product sales.
Ariad will be responsible for supplying AP23573 to Medinol, and Medinol will be responsible for the development and commercialization of the medical devices delivering the compound. Ariad said it has retained the right to enter into two additional non-exclusive agreements to develop and commercialize AP23573 in drug-delivery devices for vascular disease. Additional terms were not disclosed.
The small-molecule drug AP23573 starves cancer cells and shrinks tumors by inhibiting the cell-signaling protein, mTOR, which regulates the response of tumor cells to nutrients and growth factors, and controls tumor blood supply and angiogenesis through effects on vascular endothelial growth factor (VEGF).
AP23573 also blocks the proliferation and migration of vascular smooth muscle cells, the primary cause of narrowing and reblockage of injured arteries, and is an analog of sirolimus, another mTOR inhibitor that has been approved for use on drug-eluting stents (DES), including Cordis' (Miami Lakes, Florida) Cypher stent, the first DES to be approved in the U.S.
AP23573 is currently in Phase II clinical development in patients with solid tumors and hematologic cancers.
“We are pleased to have one of the most innovative and successful medical device companies as our first partner to develop and commercialize drug-delivery stents incorporating AP23573 — our lead mTOR inhibitor which is in Phase II oncology clinical trials,“ said Harvey Berger, MD, chairman and chief executive of Ariad. “We believe that Medinol has the design and manufacturing capabilities to develop differentiated stent platforms and polymer formulations that will enable its next-generation stents to achieve substantial penetration in a market that is estimated to grow to over $6 billion by 2008.“
Medinol is the manufacturer of the NIR line of stents, including the NIRFlex stents. Medinol invented the NIRFlex stents, which are currently available worldwide for coronary and peripheral use.
Under a 2002 agreement, Medinol and W.L. Gore & Associates (Flagstaff, Arizona) are collaborating to develop stenting solutions that incorporate key features of their respective technologies (i.e., metal stents, polymer formulations and advanced delivery systems). With this newly announced agreement, Medinol may now utilize Ariad's AP23573 drug with these combined technologies.
The companies said in a statement that they believe Gore's “unique technology“ in the polymer and biocompatible polymer areas should contribute to the design and development of the polymer layer used to control the release of the drug from the stent and to the optimization of the delivery system that will allow easy and safe use of the new system in all desired vascular sites.
Medinol's stents also are marketed and distributed worldwide by Gore, though the company still has not fully resolved its litigation with former marketing partner Boston Scientific (Natick, Massachusetts).
Medinol is currently awaiting trial in a lawsuit it filed against Boston Scientific back in 2001 (Medical Device Daily, April 9, 2001). The company contends that Boston Scientific's sale of its successful Express and Taxus coronary stents represents a breach of contract and that it is entitled to royalties on those sales.
Medinol originally entered into its relationship with Boston Scientific in 1995, agreeing to manufacture and provide its stents to the U.S. firm, with Boston Sci agreeing to market and distribute those products.
Medinol's charges stem largely from a failed attempt by Boston Sci to purchase the Israeli firm. The company said it originally was a “valued supplier“ of stents to Boston Scientific, but the U.S. firm then sought to purchase Medinol, in an attempt, it said, to better control its supplies. But Medinol rejected the proposed buyout, saying Boston Sci never made an offer that was commensurate with its value. The company claims that Boston Sci then secretly established a factory in Ireland to manufacture Medinol stents in violation of their previous agreements.
Boston Scientific counter-sued its former stent supplier, with that suit charging that Medinol failed to fulfill its obligations under a supply agreement, adding that Medinol attempted to extort concessions under threat of terminating its stent supply.
Boston Scientific also sought an injunction to stop Medinol from providing its coronary stent technology to any company other than Boston Scientific. It also asked the court to order Medinol to pay compensatory damages, punitive and multiple damages and attorneys' fees, as well as to order the company to grant a fully paid, perpetual and exclusive license to Boston Scientific to manufacture and distribute all NIR stents (MDD, May 1, 2001).