Conor Medsystems (Menlo Park, California) yesterday unveiled an agreement with Novartis Pharma (Basel, Switzerland) that it says will put it in the forefront of a dual-drug, drug-eluting stent (DES) effort and give it a large push to compete with the other DES makers now on the U.S. market or about to enter it.
The company exercised an option to obtain a worldwide, non-exclusive license from Novartis to the compound pimecrolimus (Elidel) for use with its CoStar stent. The CoStar is engineered with tiny holes, or reservoirs, into which a drug is loaded, for elution onto the artery, a system that Conor sees as more specifically engineered for drug delivery from a stent than the initial DES devices.
In March of 2005, the companies unveiled an agreement to evaluate three Novartis pharmaceutical agents - imatinib mesylate, pimecrolimus and a pre-commercial compound, midostaurin - for the potential development of a product combining a Novartis compound with Conor's reservoir-based DES (Medical Device Daily, March 17, 2005).
Conor said it selected pimecrolimus for this licensing deal based on preclinical studies of the three compounds in combination with its stent platform.
Conor will be responsible for product development, including clinical trials, manufacturing and regulatory filings. Novartis will supply Conor with pimecrolimus and collaborate with Conor on the regulatory and technical issues. Further terms of the agreement were not specifically disclosed, but Frank Litvack, CEO of Conor, told Medical Device Daily that payment in the deal includes “up-front milestone plus royalties.“
Litvack said the agreement enables the launch of a unique three-arm trial in the Middle East and Europe “later this year,“ named GENESIS, to explore a system for delivering two drugs off of the company's CoStar stent. The control arm will use its initial drug, paclitaxel, alone on a stent; the second will use pimecrolimus alone; and the third will use both the paclitaxel and pimecrolimus.
The DES will be engineered to first release the pimecrolimus drug into the artery to prevent early inflammation, with the paclitaxel then releasing more slowly “to have [a] second impact on later proliferation,“ Litvack said. The goal will be to develop a stent that targets high-risk patients, such as diabetics, he said.
In this strategy, what is left is just the bare metal stent, he emphasized.
While bare metal stents have been getting heavy negative press these days, Litvack said that after the first six to eight months they are not what is responsible for any restenosis and are highly safe.
“In terms of long-term safety,“ he said, “most people would stay with bare metal stents.“ Once in place, he said they are “extremely inert.“
Conversely, he said that there is a core of concern and opinion that first-generation DES devices, which remain in the body with the polymer used for drug loading, may have problems over the longer-term, primarily in producing thrombosis. And he surmised that, currently, many patients with these devices are at risk for late-stage thrombosis and possible death.
Litvack said that the company has not developed any timelines for regulatory filings in the U.S. assuming trial success. “We will do the European stuff first and see how it goes,“ he said.
Again assuming trial success and FDA approval, Litvack said that he is not concerned about the large market head starts by the Cypher and Taxus DES devices, or by those poised to enter the market.
He said he believes Conor is “neck-and-neck“ with Medtronic and others entering the final turn toward FDA approvals, believing that Conor's stent design is clearly superior and that its trials will prove it so.
“We believe we have a product that has many attributes that will make it attractive to physicians,“ he said. “It's extremely deliverable, and it's not coated - it's a reservoir-based technology.“ Its other highly positive features include strong trial efficacy in Europe and its being “the only product that eliminates the drug and the polymer,“ he said. And he adds his belief that the fears concerning the longer-term clinical drawbacks of drug and polymer in first-generation DES devices may eventually be borne out.
Conor, he asserted, “is heading to the U.S. market - now obviously, we have to present the data.“
Also heading for the market, he hopes, is its single-drug DES devices.
In February, Conor received CE-marking for its CoStar paclitaxel-eluting stent and it is currently being marketed in the European Union and other countries. With it, Conor is currently conducting a U.S. pivotal clinical trial, COSTAR II, to support its application for U.S. regulatory approval.
Litvack told MDD that the company expects that approval to come at the end of 2007 or early 2008.
And he said that additional programs are under way to explore the use of other compounds for the treatment of restenosis and other vascular diseases.
The push to provide a range of DES options is a two-fold strategy. Company CFO Michael Boenninghausen last year told MDD that the company wants to develop a portfolio of products rather than being a “one-trick pony.“ Additionally, it is attempting to give it more options in the case it fails in some ongoing legal battles.
A month before its March '05 agreement with Novartis, it filed a countersuit against Angiotech (Vancouver, British Columbia) in a British court to get a stent patent revoked from the drug maker. The countersuit was filed in response to a suit filed in the Netherlands by Angiotech and partner Boston Scientific (Natick, Massachusetts) for alleged patent infringement.