Indian clot-buster drug enters phase-2

New Delhi: Clot-specific Streptokinase (CSSK), a drug that breaks down blood clots, developed by an arm of the Council for Scientific and Industrial Research (CSIR), has been cleared by the office of the Drug Controller General of India (DCGI) for phase two human clinical trials.

The CSSK is the first so-called biotherapeutic drug developed in India— meaning it entailed the use of antibodies, proteins and enzymes, unlike conventional chemical drugs. If and when the drug reaches the market, it could offer an affordable alternative to expensive thrombolytic drugs used to treat patients of myocardial infarction or heart attacks, and other severe heart conditions like deep vein thrombosis.

Work on the drug began seven years ago under a partnership between the CSIR’s Institute of Microbial Technology (IMTECH), Chandigarh, and Nostrum Pharmaceuticals LLC of the US.

“Streptokinase has been modified by IMTECH through protein engineering and then made clot-specific, so that the basic risk of hemorrhage or bleeding, which is the problem with clot-busters in general, is much reduced,” said Girish Sahni, director of IMTECH and inventor of the molecule.

The effort to develop an affordable, safe clot-busting drug in India dates back to 2002 when Cadila Pharmaceuticals Ltd commercialized the first clot- buster drug and sold it for about $20 per dose. Chennai-based Shasun Chemicals and Drugs in 2009 launched recombinant streptokinase for around $50 per dose in the open market. Both drugs were developed by IMTECH.

“We went on to make a better product which would have a better clinical profile. Any drug is supposed to be better if it is more specific, if it touches the target and doesn’t touch other things in sight,” said Sahni. “What happens with a clot-buster is that it induces the body to dissolve the clots, it produces an enzyme, and lot of times there is non-specific activation. So our drug has been modified in a way so that it reacts only to a clot.” CSSK will probably cost around ₹ 1,000-2,000 per dose, which will be administered to a patient through injections. That’s a fraction of the ₹ 50,000 per dose it costs for tPA, another thrombolytic agent used worldwide for being clot-specific, Sahni said.

Since 2006, the drug has cleared tests performed on primates and been put through human safety studies in phase one trials. The drugs showed no side-effects, a major achievement for a clot-busting drug. The phase two human efficacy trials, which will begin in a few weeks, will test the drug’s efficacy in treating heart attacks.

According to the World Congress of Cardiology, heart disease will be the cause of over 40% deaths in India by 2020. Sahni said the drug will be tested on 70-100 subjects in the phase two trials, which are likely to conclude by the end of this year; the drug may be commercialised by 2016.

“It is truly a case of transitional science reaching from lab to the very threshold of a clinic and this has been possible because of the diligent pursuit of the CSIR-IMTECH team, and Nostrum Pharmaceuticals,” said T. Ramasami, secretary of the department of science and technology and director general of CSIR.