Stunted growth

Stunted growth

The cardiovascular market for pharma companies has not been very lucrative. Arshiya Khan tracks why pharma companies are shying away from research on cardiovascular disease (CVD) and what strategies will these companies adopt to meet growing patient needs

A saturated market and high cost of conducting clinical trials has kept pharma companies away from getting into cardiovascular disease (CVD) research. And this could have grave implications for public health as it comes at a time when WHO has predicted that by 2010 India will have 60 percent of the world’s heart disease patients.

Companies shying away

Though there are few companies engaged in CVD research, the segment on a whole is not very active. In the domestic space there are a few companies who have some presence in the CVD space. Suven Life Sciences has collaborated with Eli Lilly for developing CVD drugs and Dr Reddy’s Laboratories (DRL) focus on research plans to develop products in two specific therapy areas, namely, cardiovascular and metabolic disorders. However companies like Ranbaxy Laboratories, DRL, USV, Torrent Pharma, Sun Pharma, Piramal Health Care etc are already into this segment with old molecules, informs Nikunj Kanakia, CMD, Lifeline Industries.

“Pharma companies do not perceive the CVD market of high value anymore. As the cardiovascular market has become mature, new high value drugs for Alzheimer’s and oncology have gained attention from large pharma companies who are increasing their R&D spend on these diseases by reducing the spends on the cardiovascular segment”

– Muralidharan Nair Vice-President, Risk and Business Solutions

Ernst & Young

“CVD is an exploited space. Very few people today die of the disease. Current therapies are enough to ensure that safety is ensured in CVD”

– Glenn Saldanha MD & CEO

Glenmark Pharmaceuticals

“MNCs will be launching their products in India. Indian companies in collaboration with MNCs will launch their products in India. For example, in November, Lupin launched Ivabrad (Ivabradine) under a licensing agreement with Servier”

– Ramaraju Nallaparaju
Consultant, Healthcare Consulting Datamonitor, India

“Besides cardiovascular drugs, cardiologists also prescribe vitamins and nutraceuticals as well as diabetologicals and diuretics. So companies which enjoy a strong franchise with cardiologists also launch drugs in these categories and promote to cardiologists. This is a sort of adjacency expansion”

– Dr Amit Rangnekar
Centaur Pharmaceuticals

“Growth of patients in cardiac segment is fastest among all the diseases. “Therefore we are spearheading into cardiac therapeutic treatment. We are very well aware about the low success rate in research, hence we are moving with caution. Old therapies are working well but future patient needs will require higher generation molecules”

– Nikunj Kanakia CMD

Lifeline Industries

Whereas in the MNC space, a saturated market and failure of molecules to make it to the advanced stages of trials, have resulted in reduced spending on the CVD segment. The case in point is the failure of Pfizer’s Torcetrapib (that targeted the cholesteryl ester transfer protein: CETP) and AstraZeneca’s Exanta (ximelagatran) which was withdrawn from the market due severe hepato toxicity.

Another factor is the increasing ageing population and escalating healthcare costs that has led most governments of major developed countries to favour use of generic drugs. This in turn has undermined the strengths of the ‘innovator’ companies which have now restricted their R&D budgets and narrowed their R&D focus to areas that are most likely to yield results, for instance, biologic drugs for cancer and other degenerative diseases, informs Ramaraju Nallaparaju, Consultant, Healthcare Consulting, Datamonitor, India.

Also as key drugs go off patent during 2010-13 period, it will create an opportunity of $30.9 billion worth of branded drugs to generic competition. As a result of this a number of companies in the CVD segment will see their key revenue generators melt away as they lose patent protection, for example Pfizer’s Lipitor.

And in a typical landscape like India where most of the Indian pharma companies will be focusing on developing fixed dose combinations, others will be targeting patients suffering from metabolic syndrome (diabetes/dyslipidemia/hypertension), he adds.

Intense competition accompanied by high cost present obstacles for companies who want to venture into this segment. Development of CVD drugs is expensive and it is even more difficult to develop drugs with improved efficacy compared with existing products in the market.

Secondly, the number of clinical trials required to develop CVD drugs is high and therefore expensive, not to mention the degree of difficulty encountered in clinical study design for safety and tolerability. As per a report by Datamonitor on Trends in Clinical Trials, for 2005 and 2007 the largest decline in study numbers was witnessed for CVD segment which was 74 percent.

Considering this, volume of clinical trials in CVD has decreased for many global pharma companies like Abbott, AstraZeneca, Boehringer, Sanofi-Aventis, Wyeth, and this is reason enough for global companies to re-allocate their R&D priorities, feels Muralidharan Nair, Vice-President, Risk and Business Solutions, Ernst & Young.

Adding to this there is an increase in clinical trial costs due to requirements of large patient sample size. Also, as incremental benefits of new molecules in the CVD space is narrow, it needs higher sample sizes thereby inflating drug development costs (5000-7000 patients are required for clinical trials for a typical CVD molecule as compared to 2000-3000 for other therapeutic areas). Adding to this, the inability to prove efficacy differentiation and classify safety parameters has also led to a slowdown in this area.

Emerging areas

Over the last few years pharma companies have been focussing on anti-cancer, anti-infectives and central nervous system (CNS) therapies. And this has also to some extent shifted the focus of pharma companies. “Pharma companies do not perceive the CVD market of high value anymore. As the cardiovascular market has become mature, new high value drugs for Alzheimer’s and oncology have gained attention from large pharma companies who are increasing their R&D spend on these diseases by reducing the spends on the cardiovascular segment,” believes Nair. He cites an example. Under a re-organisation of R&D priorities, Pfizer is exiting R&D from CVD (including atherosclerosis, hyperlipidemia, and heart failure), a therapeutic area that has been the drug giant’s cornerstone, to focus on market opportunities in areas like oncology and diabetes.

Also, many pharma players believe that the Indian CVD segment is a mature and saturated market with large number of already existing molecules. Highlights Glenn Saldanha, MD and CEO, Glenmark Pharmaceuticals, “CVD is an exploited space. Very few people today die of the disease. Current therapies are enough to ensure that safety is ensured in CVD.” He believes the two unmet medical needs are in the area of oncology and CNS. However inflammation and metabolic disorders is something that Glenmark is committed to. We cannot change that now because the challenges to move into a new therapeutic segment are very significant, he adds.

Also lower probability of approvals in the segment has been a reason for not many companies being affirmative about the CVD space. A Tufts Impact Report of May-June 2006, examining drug approval trends in the period 1993-2002 indicated that the probability of a drug gaining approval for launch varied according to therapy. Respiratory, oncology, immunologic and anti-infectives had the highest approval success rates, while gastro-intestinal/ metabolism, CNS and CVD drugs had the lowest approval rates.

Strategies of Indian companies vs MNCs

According to Nair, the Indian CVD market is well served with more than 1800 brands for 140 molecules. The average sale per brand is less than $0.45 million. Torrent had 40 brand introductions in 2007, Lupin had 16, Zydus Cadila,10. In such a scenario, effective sales and marketing strategies would be the key focus of companies in this space, feels Nair. He adds, patented products will be launched over the next few years; however these would be affordable only to the elite section of the population due to its high costs.

CVD segment is highly capital intensive and technical. Since it needs high investment, only big players are entering into it. We would rate success in research of CVD as 40:60 percent, says Kanakia. Looking at the success failure ratio many companies have strategically collaborated to develop molecules or have devised a plan where they decide which molecule to back. Dr T Rajamannar, Director & Executive Vice President, Sun Pharma Advanced Research Company (SPARC), informs, that as a strategy, they prefer a focused approach, and at SPARC they have looked at therapeutic analogs and prodrugs which build on known science. The company has four drugs in the pipeline but none in the area of cardiology.

But as Kanakia points out, growth of patients in cardiac segment is fastest among all the diseases. “Therefore we are spearheading into cardiac therapeutic treatment. We are very well aware about the low success rate in research, hence we are moving with caution. Old therapies are working well but future patient needs will require higher generation molecules.”

Future trends

Lack of new products and the inability to incorporate new diseases to grow the franchise will constrain the expansion of the treated population and, in turn, the market size. By 2016, it is expected that only 16 percent of CVD sales will come from new products, highlights Nair.

According to Nallaparaju, MNCs will be launching their products in India. Indian companies in collaboration with MNCs will launch their products in India. For example, in November, Lupin launched Ivabrad (Ivabradine) under a licensing agreement with Servier.

Kanakia offers a different view. According to him, as cardiac ailments can be treated with different range of drugs like sartan, statin, beta blocker, isosorbide etc different players will adopt different tactics to grab major market share. DRL’s strategy of developing polypills will be another option for domestic companies.

Gene therapy and stem cell technology for CVD will hold substantial commercial potential. The other model that is more likely to exist according to Dr Amit Rangnekar, Centaur Pharmaceuticals is that, besides cardiovascular drugs, cardiologists also prescribe vitamins and nutraceuticals as well as diabetologicals and diuretics. So companies which enjoy a strong franchise with cardiologists also launch drugs in these categories and promote to cardiologists. This is a sort of adjacency expansion.

As the global economy slips further into a recession, pharma companies who pulled out of CVD research are not likely to re-allocate R&D resources to this segment. But this leaves the field open to a persevering few, who are willing to take the risks in the hopes of reaping the rewards a few years down the line.

arshiya.khan@expressindia.com