Medical Device Daily Associate

In a move that, at least in part, could be attributed to a pending lawsuit with Angiotech Pharmaceuticals (Vancouver, British Columbia) over rights to the use of that company's paclitaxel compound on a drug-eluting stent (DES), Conor Medsystems (Menlo Park, California) reported that it has signed an agreement with Novartis Pharma (Basel, Switzerland) granting Conor the right to evaluate three Novartis pharmaceutical compounds for the potential development of a new DES product.

Conor will evaluate the compounds Gleevec (imatinib mesylate), Elidel (pimecrolimus) and a pre-commercial compound, midostaurin, for the potential development of a new product utilizing its reservoir-based DES devices to treat restenosis and other vascular diseases.

Imatinib mesylate belongs to a class of drugs collectively known as signal transduction inhibitors. It is an inhibitor of several protein-tyrosine kinases including PDGF that are believed to play a role in reducing cell proliferation and therefore may have applications in the treatment of restenosis. Pimecrolimus is a cell-selective inhibitor of the production and release of pro-inflammatory cytokines. It is believed that inflammation is one of the key mechanisms in restenosis as well as other vascular inflammatory diseases such as unstable plaques. Midostaurin is an inhibitor of both FGF protein kinases and extracellular matrix synthesis associated with vascular endothelial dysfunction such as in the restenosis process in diabetic patients.

The company said it will initially evaluate all three compounds and, based on results, will have the option to obtain a worldwide, non-exclusive license to develop and commercialize products combining Conor's drug-eluting, reservoir-based Costar cobalt chromium stents with one of the three compounds evaluated.

If Conor exercises its option to license one of the compounds, the company will be responsible for product development, including clinical trials, manufacturing and regulatory filings, and will pay Novartis licensing fees, milestone payments and royalties on product sales.

Fort its part, Novartis will supply Conor with the compounds and will collaborate with the company on regulatory and technical issues. Further terms of the agreement were not disclosed.

While CFO Michael Boenninghausen told Medical Device Daily that this agreement with Novartis is in line with Conor's plan to "create a portfolio of products" and to prevent them from becoming a "one-trick pony" company, this partnership news follows close on the heels of Conor's disclosure last month that it had filed a countersuit against Angiotech in a British court to get a stent patent revoked from the drug maker (Medical Device Daily, Feb. 22, 2005) and could provide a back-up compound should the courts rule against Conor.

The disputed patent relates to coronary stents coated with paclitaxel – a cancer drug that also has anti-inflammatory properties – and a polymeric carrier. Conor maintains that its lead product candidate is different from the typical DES.

Boenninghausen said that the company's stents have been specifically designed for vascular drug delivery, in contrast to existing DES devices, primarily conventional bare-metal stents coated with a polymer and a drug.

He noted, instead, that the Costar incorporates hundreds of small holes, each acting as a reservoir into which the company can load a drug/polymer composition. This design, he added, enables a wider range of drug therapies – including combinations of multiple compounds – and provides greater control over the direction and rate of drug release, which should allow for more targeted treatment within the artery and more efficient use of the therapeutic agent.

This distinction makes the Costar "very different from coated stents," Boenninghausen said, a differentiator the company hopes will be upheld by the court.

Aside from that distinction, he said that Conor's lawsuit charges that the Angiotech patent "lacks novelty," since the technology is available in publications and thus common knowledge.

The company's countersuit came about two weeks after Angiotech and partner Boston Scientific (Natick, Massachusetts) sued Conor in the Netherlands for alleged patent infringement.

Angiotech reported its suit against Conor after the European Patent Office upheld the validity of Angiotech's patent, including claims involving stents coated with paclitaxel and a polymeric carrier.

Boenninghausen noted that even if Conor ultimately does not prevail in the suit, because of the systems' unique qualities – including the non-deforming holes into which compounds are placed – it can be used with a "universal" amount of different polymers and drugs, including water-soluble compounds, as compared with conventional surface-coated stents, hence the Novartis agreement.

While he said that the company reported positive results of its EuroSTAR study evaluating its CoStar paclitaxel-eluting stent in a complex patient cohort earlier this month at the American College of Cardiology (Bethesda, Maryland) annual meeting in Orlando, Florida (MDD, March 8, 2005), Boenninghausen said Conor "believes there is still room for improvement. This is part of our strategy to bring additional drugs."

An intriguing new compound being studied in this partnership is the preclinical midostaurin compound, particularly because of its potential to enhance the treatment of restenotic diabetics, a large, difficult-to-treat subset of the patient population that experiences restenosis.

"The thought is maybe this drug, since it targets the [molecular] pathway that tends to be very active in diabetics, may be especially appropriate for the diabetic population," he said, adding: "We're actually trying to push the envelope and find molecules that can still treat patients that are not being well-treated now with the current therapies."

In a prepared statement, Frank Litvack, MD, chairman and CEO of Conor added to Boenninghausen's assertions about the need for different compounds.

"We believe that the results of the recently presented ISAR-DIABETES, Taxus V and SIRTAX trials clearly indicate a need for improved efficacy of drug-eluting stents in real world patient populations," Litvack said. "The Novartis agreement has the potential to expand Conor's development pipeline by enabling us to explore the therapeutic potential of Novartis' leading agents with our proprietary stent platform. Given that Conor's reservoir technology is designed to optimize release kinetics, as well as to deliver multiple drugs with independent mechanisms of action, we are excited to initiate research with the aim of developing important next-generation drug-eluting stents."

Boenninghausen estimated it will take about a year to fully evaluate the three Novartis compounds. Assuming that the company is able to find a suitable candidate from the three and has successful clinical trials, he said the said Conor could have a new product on the European market sometime in 2007, and U.S. approval in 2009.