New Delhi: Cardiologists in several parts of the country say that demand for a twice-a-year injectable drug to reduce levels of low-density lipoprotein cholesterol (LDL-C)— commonly called bad cholesterol—has exceeded expectations within months of its launch in India. High levels of LDL-C are among the leading causes of heart attacks and strokes, the two top reasons for mortality in India.
Inclisiran, developed by Swiss pharma giant Novartis and launched in India in January this year under brand name Leqvio, is indicated, for now, for patients with high LDL-C as a third line of treatment if statins—the most widely used drug for lowering cholesterol—and a few other second-line agents fail or if someone is intolerant to statins.
After the initial loading dose of the drug, which is administered through a subcutaneous injection, the next dose comes at three months, and then every six months.
While many cardiologists say it has been an excellent addition to their arsenal in fighting LDL-C, they also emphasise that the response to inclisiran in India may have been tempered by concerns over its high cost and potential side effects in the long term.
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Who can benefit from the drug
A large survey carried out by the Indian Council of Medical Research (ICMR) and the Madras Diabetes Research Foundation, published in The Lancet last year, had shown 81.2 percent Indians have dyslipidemia and 20.9 percent—or 185 million—have high levels of bad cholesterol.
Dyslipidemia is a disorder marked by abnormal levels of lipids, such as cholesterol, LDL-C, triglycerides, and high-density lipoprotein cholesterol (HDL-C), in the blood.
The Cardiological Society of India, in its first ever India-specific lipid management guidelines that came out in July this year, had said that high-risk individuals, such as those with diabetes or hypertension, should aim for an LDL-C level below 70 milligrams per decilitre.
Inclisiran is recommended for individuals whose cholesterol levels remain high despite being on statins, making it an alternative for those who struggle to control their LDL-C effectively with existing treatmenstts.
It may also be beneficial for people with a strong family history of cardiovascular events or those who have experienced recurrent heart attacks or strokes, where aggressively managing LDL cholesterol levels is crucial for reducing the risk of future incidents.
Additionally, inclisiran is advised for patients who experience significant side effects from statins, such as muscle pain or other adverse reactions, and are unable to tolerate them.
Dr Ashok Seth, interventional cardiologist and chairman of Fortis Escorts Heart Institute, New Delhi, said that inclisiran has been a tremendous addition in the therapies available to lower cholesterol for a significant number of Indians who are susceptible to adverse cardiovascular events due to high cholesterol.
“There are nearly 15 percent of all patients with high cholesterol who struggle to keep their cholesterol levels within limits despite trying the first two lines of treatment. For them, inclisiran has been a very potent tool and I have seen dramatic results in many of my patients who have tried it so far,” he told ThePrint.
Despite the high cost of the drug—each injection costs nearly Rs 1.2 lakh—Seth said many patients with high LDL-C were asking for the drug, bypassing the first two lines of treatment.
“This, however, is not suggested at this point,” he said.
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Specialists vouch for drug
Some other heart specialists, too, vouched for the drug.
Dr Sunil Dwivedi, consultant cardiologist with Manipal Hospital in Bengaluru, said he has used the drug in some of his patients who were either not responding to traditional cholesterol-reducing statins, couldn’t tolerate statins, or who had multiple heart events.
“After the second injection, their cholesterol levels dropped to the target range, which is very promising, and none of them experienced any side effects. True to the clinical trial data, this drug has been very effective in such cases so far,” Dwiwedi said.
In response to a query by ThePrint, Amitabh Dube, country president and managing director, Novartis India, said that it has been eight months since the launch of inclisiran in India and, over these months, the company has received positive feedback about the molecule from cardiologists across the country.
“We are happy to learn that doctors have been able to help their patients reach and sustain their target LDL-C or bad cholesterol levels and in turn improve their heart health,” he said.
Dube added that the firm is witnessing a month-on-month increase in adoption of the molecule, but did not share the specific numbers.
“It is heartening to see our purpose of improving and extending people’s lives come alive in the wake of the snowballing incidence of heart-related mortality and morbidity in India,” he also said.
How it works
Statins are the most commonly used pharmacotherapies to lower cholesterol levels and work by inhibiting an enzyme called HMG-CoA reductase that is involved in the synthesis of cholesterol in the liver.
According to Dr Amit Bhushan Sharma, director and unit head of cardiology with Paras Health in Gurugram, inclisiran has shown promise due to its novel mechanism of treatment and convenient dosing regimen.
As a gene-silencing drug, it targets the PCSK9 enzyme, enhancing the liver’s ability to remove LDL cholesterol, which could significantly benefit high-risk patients, especially those who do not respond well to statins or experience severe side effects.
With just two doses needed per year after an initial loading phase, inclisiran provides a convenient alternative to the frequent dosing required by other cholesterol-lowering medications, which may improve patient adherence and overall outcomes, he said.
The launch of inclisiran comes six years after Hyderabad-based pharmaceutical major Dr Reddy’s Laboratories, under partnership with American biotech company Amgen, launched evolocumab—under the brand name Repatha—the first PCSK9 inhibitor in India.
Repatha, which costs nearly Rs 18,000 per injection, is also indicated for use by statin-intolerant patients or those with high bad cholesterol despite treatment with statins.
This drug, however, has to be administered as an injection every 15 days.
According to the American Heart Association, the main difference between evolocumab and inclisiran is that while the former delivers antibodies to block the PCSK9 gene, the latter switches it off. This means the PCSK9 protein is not made in the liver and more LDL receptors can return to the surface of the liver and continue to remove LDL cholesterol from the blood—thereby working for a longer period, nearly six months.
“Because inclisiran is effective for six months in high-risk patients, it has a clear advantage and can lead to a much higher degree of treatment adherence,” Seth pointed out.
Dr J.P.S. Sawhney, chairman of the department of cardiology at Sir Ganga Ram Hospital in Delhi, underlined that while most of the patients have received only two doses of inclisiran so far, evidence from clinical trials has shown that it reduces LDL-C by 50 percent.
“The advantage of inclisiran is that it causes sustained reduction of LDL-C and there is no LDL-C variability. It has to be given only two times a year,” he said.
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Cost, long-term safety data still concerns for many
While many patients who have a high capacity to pay and have been prescribed the drug are opting for inclisiran, its affordability is also a concern for a large number of patients.
Sharma of Paras Health also emphasised that despite the benefit it promises, the response to inclisiran in India may have been tempered by concerns over its high cost and potential side effects in the long term.
“One its affordability is a major barrier, particularly in a country where cost-effective treatments like statins are widely available and preferred. Additionally, there are concerns about possible long-term side effects due to its extended duration of action, as any adverse effects could be challenging to reverse,” he said.
To prevent high cholesterol, one should prioritise lifestyle changes, such as maintaining a healthy diet, engaging in regular exercise, and refraining from smoking, the cardiologist said.
Seth too, agreed, that long-term safety data on inclisiran is yet to be seen and as such it should not be hyped as a preferred treatment of bad cholesterol in all patients.
“Inclisiran is the latest kid on the block. Maybe in future, if it proves to be a safe alternative to the existing lipid-lowering drugs, it can go on to become a second line of treatment but for now, we have to reserve it for 15-20 percent of the patients who are not getting the desired result with other therapies,” he said.
(Edited by Sanya Mathur)
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