The ongoing drug coated stent war among manufacturers to grab the predicted $5 billion per annum global opportunity could subject the Indian cardiac patients to undergo unapproved clinical trials of drug eluting stents (DES), unless the government immediately brings in proper regulations to regulate such devices, alleges a section of experts and regulators.
Sources say, according to their knowledge, many of the companies are dumping drug eluting stents worth crores of rupees to their distributors, who in turn supply it directly to the hospitals in accordance to the demand. None of the products is available in the open market and most of the regulatory officials are yet to even see a stent, confess senior drug control officials.
Sources cite drug coated stents, to prevent restenosis or reclosure of the artery, are a recent innovation and the manufacturers are still in the process of generating adequate data to substantiate their claims through worldwide clinical trials for approval in the stringent US and European markets. Even the two established and highly successful products, which control lion’s share of the existing market, the Cypher stent of Cordis/Johnson & Johnson and Boston Scientifics’ Taxus, got the US FDA and European approval only recently. While Cypher, the first approved drug coated stent, was cleared for sale in US only during April 2003, Taxus got the nod almost a year later during March 2004. US FDA asked J&J/Cordis to subject Cypher for further trials in 2000 patients to generate data on long-term usage and side effects while approval was given in the US. The approved shelf life for these stents are one year in US, and 18 months outside US, sources point out.
Boston Scientific, the market leader and the first to come up with a new second-generation Taxus Liberte drug-eluting stent, launched the product during January 2005 in 18 countries, including India. Interestingly, the launch was restricted only to countries like India, Bahrain, Chile, Costa Rica, Dominican Republic, Indonesia, Kuwait, Lebanon, Malaysia, Panama, Peru, Philippines, Saudi Arabia, Singapore, South Africa, Thailand, Turkey and Venezuela. The company has already announced it completed enrollment in the transitional phase of the world's largest drug-eluting stent registry, the OLYMPIA registry, to enroll more than 30,000 patients at more than 600 centers in the United States, Europe and other international locations. US FDA is yet to approve Taxus Liberte, and the company expects US nod only by mid-next year. The company has already sold over one million Taxus stents globally, including thousands of stents in India.
With a US trial already underway, Cook Group is in the process of bringing out the world's first paclitaxel-eluting stent for peripheral artery disease (PAD) to market by launching an international clinical trial. The global clinical investigation of Cook's Zilver PTX drug coated stent has enrolled 760 patients at 50 investigational sites in Europe, Asia, Australia and Canada, according to the company. Another manufacturer Guidant says it is conducting a large-scale pivotal clinical trial to evaluate the safety and efficacy of its stent, XIENCE V, an everolimus eluting coronary stent. Abbott has enrolled patients in the North American phase of its Zomaxx II trial, with the permission of US FDA. This new stent uses a drug coating different than the current ‘limus’ and paclitaxel varieties. Similarly, Conor Medsystems’ Costar and Unistar are undergoing various ‘clinical studies’ to get approval from the US and European regulatory authorities. Medtronic is also in the final phase of its Endeavor clinical program aimed at gathering clinical data to secure approval from US FDA for its drug-eluting stent.
If this is the case with multinational medical device manufacturing majors having R&D capabilities, the lesser-known companies are also trying to corner a pie of the global market. “To our knowledge, 10 to 20 companies or their distributors are selling in India. Even Korean and Chinese companies are selling their DES in India,” says Maharashtra FDA Commissioner, Ramesh Kumar.
“I heard about a Chinese DES named Firebird, but yet to see it. Same is the case with Korean companies. I attended a medical conference in Paris a few years ago where the Gujarat-based manufacturer of DES presented elaborate data of their product. Small manufacturers lack adequate resources to generate and present data to support their claims for approvals with US FDA or European Union, in comparison to established products from the west. As far as a doctor is concerned, he may prefer only the best, as no cardiologist wants his patient to come back to the hospital,” said a leading cardiologist from Chennai.
The Maharashtra FDA had served notices to distributors of some of these companies, like Johnson & Johnson, Boston Scientific, Bangalore-based medical devices company Vascular Concepts (pronova), Singapore-based Intek and its distributor Elder Pharma (Apollo), B. Braun (Coroflex Please), Medtronic (Endeavor), Sarin of Germany and its distributor Strenco (brand Jenus), Conor Medi Systems’ Indian distributor IUTL etc.
Sources say usage of these stents is rampant in India, though majority of the cardiologists prefer only Cypher and Taxus stents. “Knowingly or unknowingly these stents are being experimented on Indian patients, as part of generating business and clinical data for these products to prove claims to get approval from the strict US and European regulators. It is high time the government comes up with a regulatory mechanism,” opined sources.
As Pharmabiz reported, while the Drug Controller General of India (DCGI) cites lack of rules in the Drugs &Cosmetics Act to regulate medical devices, the recently met Drug Consultative Committee (DCC) is of the opinion to wait for evolving a medical devices act to take up the matter of regulating drug coated stents. The issue surfaced early this month following the Maharashtra FDA’s decision mandating marketing approval from DCGI or to submit US FDA or CE approvals to sell drug-eluting stents in the state.