The Clot Specific Streptokinase (CSSK), a novel patented thrombolytic biopharmaceutical therapeutic protein drug licensed from the CSIR-Institute of Microbial Technology (CSIR-IMTECH), Chandigarh, a constituent institute of the Council of Scientific and Industrial Research (CSIR), has received permission from the Drugs Controller General of India (DGCI) to conduct Phase-2 human clinical trial to test the efficacy of CSSK in the patients of heart attack, a condition known as Acute Myocardial Infarction. M/s Symmetrix Biotech Pvt. Ltd. has been carrying out the clinical development of CSSK, also known as SMRX-11.
This was announced by Dr. T. Ramasami, Secretary, DST and DSIR and Director General of CSIR here in New Delhi today. Dr. Ramasami congratulated both Nostrum Pharmaceuticals and IMTECH. He said, “This has been an exemplary and diligent pursuit of translational science from lab to the very threshold of clinic. Upon successful development, CSSK would be the first patented biopharmaceutical drug developed in India and I therefore congratulate Dr. GirishSahni and his team at ICSIR-MTECH as well as Dr. Mulye of Nostrum for being partner with CSIR/ IMTECH in this endeavor ”.
“This has been the culmination of seven years of long and meticulously carried out developmental process of this molecule under a unique and successful public-private partnership between CSIR-IMTECH and Nostrum Pharmaceuticals of the US (the parent company of Symmetrix Biotech Pvt. Ltd.)” said Dr. Girish Sahni, Director, CSIR-IMTECH and innovator of this molecule.
Dr. Sahni emphasized that the CSSK is unique in that it has a hugely reduced risk of bleeding during the treatment, which makes it a distinctively improved drug compared to several currently employed thrombolytic drugs where the risk of bleeding exists to varying degrees. Besides being safe and effective, CSSK would also be a much cheaper and affordable alternative to the currently available expensive thrombolytic drugs and will thus address the needs of the larger masses of the country, he added.
A recent report in the international journal,Nature Biotechnology (2012, Volume 30-10, 903) pointed highlighted: “If CSSK is approved, it could be India’s answer to more expensive thrombolytic agents such as tPA”.
Earlier, in July 2006, CSIR-IMTECH had licensed CSSK to Nostrum Pharmaceuticals of the USfor clinical development through its Indian subsidiary,Symmetrix Biotech Pvt. Ltd. Under this cooperation since 2007, several important developmental milestones of CSSK were achieved:
1. Development of a cGMP process to produce CSSK batches for preclinical and clinical trials
2. Achievement of a successful proof of concept of efficacy of CSSK in primates (cynomolgus monkeys)
3. Conduct of successful preclinical toxicology trials on CSSK in cynomolgus monkeys
4. Successful completion of Phase-1 clinical trial on CSSK in healthy human volunteers, which was conducted early last year as per the permission and a protocol approved by DCGI.
This successful Phase-1 clinical trial demonstrated the safety of CSSK which was given as a single bolus dose to healthy human volunteers who tolerated the drug very well with no adverse effects without any side effects which is otherwise sometimes observed in a clot buster therapy with streptokinase particularly, such as increased risk of internal bleeding due to a drop in blood-fibrinogen levels.
Dr. Nirmal Mulye, President of Nostrum Pharmaceuticals, LLC, New Jersey, USA said, “it is a proud moment both for his company and CSIR-IMTECH….CSSK development has come a long way since we licensed the molecule in July 2006. It is now on the threshold of success since we have already seen a successful efficacy in cynomolgus monkeys and a very safe profile of tolerability, pharmacokinetics and pharmacodynamics in healthy human volunteers. The cooperation of CSIR, and IMTECH, especially of Dr. Girish Sahni and his scientific team, has been the key to our success. We will very soon be embarking on the Phase-2 clinical trial following the recently obtained permission from DCGI”.
In the past, CSIR-IMTECH has licensed technologies for indigenous production of biogeneric versions of the life saver drug, streptokinase to Indian pharmaceutical firms. These products (Natural Streptokinase and recombinant Streptokinase) are selling well and account for a major share of the thrombolytic market.
Unlike the biogenerics, the newer therapeutic CSSK is a novel thrombolytic with reduced side effect of bleeding. it has been designed by protein engineering in such a way that unlike streptokinase, it is activated only upon coming in contact with the blood clot, and as a result the clot dissolving substance plasmin is produced by CSSK only at the site of the blood clot. Consequently, a very small amount of plasmin is generated, which quickly dissolves the blood clot without harming the precious blood component, fibrinogen, a protein that is necessary for clot formation, thus greatly thwarting the possibility of bleeding during clot dissolution-which otherwise can often lead to the patient’s death.
The safety and tolerability of CSSK has been very convincingly established in healthy human volunteers during the recently conducted, DCGI approved Phase-1 clinical trial in India. A maximum dose of up to 20mg CSSK was given to healthy human volunteers with no sign of any adverse effect. More importantly, the blood fibrinogen levels in these volunteers remained unchanged following the CSSK dosing. Previously, the efficacy of CSSK had been successfully demonstrated in cynomolgus monkeys where it was shown to dissolve the newly created blood clots in the animal’s femoral artery without destruction of the blood fibrinogen levels.
Starting, during the latter part of this month of February 2014, the efficacy of CSSK will be tested in human patients of heart attacks (Acute Myocardial Infarction or AMI) in a DCGI approved protocol for Phase-2 human clinical trial in India. Based on the strength of its safety profile, CSSK is expected to be a leading thrombolytic drug worldwide upon successful clinical development.