HONG KONG – Regulators in India have approved phase II trials for the protein drug that targets blood clots and could help treat heart attack patients with fewer risks and side effects than existing treatments. It may be the first biopharmaceutical compound fully developed in the country.

Last week, the Drugs Controller General of India (DCGI) gave Mumbai-based Symmetrix Biotech Pvt. Ltd., a subsidiary of Nostrum Pharmaceuticals Inc., of Kendall Park, N.J., the green light to carry out a phase II human clinical trial for clot specific streptokinase (CSSK), a thrombolytic therapeutic protein drug. Symmetrix licensed CSSK from the Council of Scientific & Industrial Research’s Institute of Microbial Technology (Imtech), which is based in Chandigarh, India.

The trial is scheduled to begin this month and will see CSSK tested on human patients with acute myocardial infarction (AMI).

“This has been an exemplary and diligent pursuit of translational science from lab to the very threshold of clinic,” said T. Ramasami, secretary to the Department of Science and Technology of India, in a Feb. 13 statement to announce the approval of the trials. “Upon successful development, CSSK would be the first patented biopharmaceutical drug developed in India.”

The aim of the trial is to test the efficacy of CSSK on heart attack patients, said Ramasani.

Symmetrix has been developing CSSK under the name SMRX-11. If the trials are successful, the company expects the drug to become a leading thrombolytic drug with global appeal.

If CSSK makes it through trials, it may become the first patented biopharmaceutical drug developed in India.

The drug has been in development for seven years through a public-private partnership between the institute and Nostrum Pharmaceuticals, the U.S.-based parent company of Symmetrix, said Imtech’s Girish Sahni, who invented the drug and led its development.

CSSK reduces the risk of bleeding during treatment for heart attacks, thus improving on existing thrombolytic drugs.

The commonly used Streptokinase works by creating large amounts of blood plasmin, which helps dissolve clots, through indiscriminate plasminogenolysis. But this approach damages fibrogen, a blood protein used in the clotting process. As a result, a risky side effect of Streptokinase is that it can lead to internal bleeding.

Unlike traditional streptokinase, CSSK causes plasminogenolysis only when confronted with a blood clot. The targeted approach helps CSSK avoid dangerous internal bleeding. CSSK targets blood clots. If it does not find one, it circulates through the blood stream like a harmless protein. In this way CSSK generates only a minimum amount of plasmin, thus limiting the damage to fibrogen.

Protein engineering is used to create the targeting mechanism for CSSK.

The efficacy of CSSK had already been demonstrated in monkeys and preliminary animal toxicological results showed it to be safe, in high doses, in rats and dogs by the time Symmetrix acquired the license.

The safety of the drug was proven during a phase I trial that involved giving out single doses of CSSK to healthy human volunteers. The trial showed no adverse effects frequently seen in clot busting therapies with streptokinase, in particular internal bleeding due to drops in the levels of blood fibrinogen.

During the phase I trial, maximum doses of 20 mg of CSSK were given to the volunteers, who showed no adverse effects. Their fibrinogen levels were unchanged after taking CSSK.

CSSK also is likely to be much cheaper Streptokinase, which is often too expensive for most patients in India and other developing markets.

Nostrum acquired the license for CSSK for worldwide clinical development and marketing from Imtech in 2006.

“CSSK development has come a long way since we licensed the molecule in July 2006,” said Nostrum president, Nirmal Lulye, in a statement.

Imtech has out-licensed other products in the past to Indian companies, in particular biosimilar versions of streptokinase including both natural streptokinase and recombinant streptokinase.

In February 2009, Nostrum acquired another worldwide license from Imtech to develop and commercialize Caerulomycin A and various derivatives and analogues. Caerulomycin is a small molecule that shows promise in immunosuppression of T cells and B cells, said Sahni. It has the potential to be developed into a drug to prevent organ transplant rejection and some autoimmune disorders.

Imtech was established in 1984, originally to focus on microbial biotechnology.