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Does Patent Expiry Matter Less For Difficult To Copy Drugs?

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“Patent expiry matters much less for difficult to copy drugs”.

Not so long ago, this is what many used to believe in the pharma industry. However, looking at the current trend involving the tech savvy generic players, it appears, gone are those days even for the home grown companies in India. As we witness today, a number of global generic players, including some from India, are overcoming the tough challenge of technological barrier of the original drugs with technology, boldly and squarely, and that too with reasonably good speed.

A global CEO felt quite the same:

Possibly encouraged by this commercial dogma, the Chief Executive of GlaxoSmithKline (GSK) Sir Andrew Witty reportedly felt in not too distant past that his company’s blockbuster drug Advair/Seretide, used for the treatment of asthma, would continue to remain a major product, despite losing US patent in end 2010. Witty thought so considering the intricate technology involved in making its high tech inhalation drug delivery system with exacting precision.

Technology based entry barrier:

Although, Advair/Seretide is a respiratory inhalation drug, it is not quite like a typical aerosol inhaler consisting of a pressurized canister filled with liquid medicine formulation. In such system, as the canister is compressed, the liquid inside comes out as a spray that is breathable in an amount as required for desirable clinical efficacy for the patients.

With the application of complex technology, Advair/Seretide was formulated not as a liquid, but as pre-determined fixed dose combination of powders that patients inhale into their respiratory tracts with a device called ‘Diskus’, which involves a complex and difficult to copy inhaler technology with a long patent life.

This precision technology was expected to create the requisite entry barrier for generic equivalents of this important medicine.

“Diskus” patent to continue:

It is important to note, though Advair/Seretide had gone off patent in end 2010, the patent protection for the “Diskus” device that dispenses the powder version of the fixed dose drugs combination, continues till 2016. For the inhaler device that dispenses the aerosol version of the same drugs, the patent remains valid until 2025.

New USFDA guidance:

Keeping these factors in mind, the USFDA in its latest guidance has clearly enunciated the characteristics that an inhaler should have, including a similar size and shape to Diskus. This new USFDA guidance for inhaled drugs, like Advair/Seretide, now requires only “relatively basic” preclinical tests and a short clinical trial.

Many believe that this new guidance is mainly to ensure that other generic devices also qualify for the GSK’s asthma drug combo, after its patent expiry.

Nevertheless a challenging task:

Despite this new USFDA guidance for inhaled drugs, some large generic manufacturers apprehended, even way back in 2010, that they doubt whether it will be possible for them to adequately replicate Advair/Seretide to meet the stringent “substitution” requirements of the USFDA on generics. This is exactly what Witty had envisaged earlier.

Almost two years after its patent expiry, in October 2012, the world’s largest generic drug maker Teva also announced that the company does not expect to see true substitutes for Advair/Seretide before 2018.

No immediate sales impact post-patent expiry:

As a result, in 2012, even a couple of years after its patent expiry, Advair/Seretide could successfully weather the impending storm, though GSK reported a lackluster overall business performance. The brand at that time was virtually immune to substitution threats from generic equivalents. The key reason being, as stated above, much unlike a patented chemical drug substance, the ‘Diskus’ system of the GSK inhaler is a hell of a task to copy by meeting the regulatory requirements of substitution.

In 2013, close to three years after its patent expiry, Advair/Seretide ranked fourth within the top 10 global best-selling drugs of that year, clocking annual revenue of US $8.25 billion.

The first competition:

In the midst of all these, the first generic equivalent of Advair/Serevent with a new inhalation device, carrying a name AirFluSal Forspiro from the Sandoz unit of Novartis, started warming up to obtain regulatory approval from several countries within the European Union (EU).

The product was first approved in Denmark on December, 2013 with subsequent marketing authorizations received in Germany, Sweden, Hungary, Romania, Bulgaria, and Norway.

The heat started being felt now:

The overall position of the brand started changing thereafter. According to published reports, sales trend of Advair/Seretide in Europe and other markets are on the decline in 2014. In Europe, the drop was around 3 percent and in the US around 19 percent in the last quarter, due to a combined impact of many factors.

According to Bloomberg, the sales of Advair/Seretide are expected to drop from US$8.25 billion in 2013 to US$5.9 billion in 2016 with the entry of generics.

A large and growing market to invest into:

According to the World Health Organization (WHO), in every 10 seconds, Chronic Obstructive Pulmonary Disease (COPD) that includes conditions such as chronic bronchitis and emphysema kills one person globally. It is expected to be the third leading cause of death worldwide by 2030.  However, though more number of people suffers from asthma globally, its mortality rate is still much less, WHO says.

Bloomberg estimates that COPD market, including asthma, is expected to reach over US$30 billion by 2018.

Cipla came next crossing the ‘technology hurdle’:

Though the leader in the global generic market – Teva, expressed its inability to introduce the generic version of Advair/Seretide before 2018, this month, the Indian pharma major Cipla introduced its version of the product in two European countries, just next to Novartis. Consequently, Cipla demonstrated its ability to overcome the technological hurdle of the product faster than most others and mastering the intricate NDDS technology in record time, with precision.

The Cipla product is named as ‘Serroflo’ in Germany and ‘Salmeterol/Fluticasone Cipla’ in Sweden. As reported in the media quoting Cipla Chairman Dr. Yusuf Hamied, the product has also been launched in Croatia. By now, Cipla has obtained regulatory approvals of this product in 10 countries in total, with an approval pending in the GSK’s own domestic turf, the United Kingdom (UK). Other country-wise launches in Europe would probably take place much before the end of 2014, according to Dr. Hamied.

The product is expected to be launched in the US in the next three to four year’s time, though one media report mentioned about its 2015 launch in that market. Dr. Hamied also said that his company is now planning its first-ever manufacturing plant in America, which might focus on producing HIV medicines.

On a conservative estimate, the market analysts expect Cipla to generate around US$50 million in sales from the EU markets by 2016 and around US$110 million by 2018, as the company gains increasing market access with not more than 4-5 generic competitors competing in this segment.

Be that as it may, getting regulatory approval for launch of a generic version of Advair/Seretide in the regulated markets, by itself, is a huge achievement of technological prowess that Cipla has demonstrated, yet again.

Not too many generic competition expected:

Because of high quality technological requirements to develop a replaceable generic version of the GSK product, not too much competition is expected in this segment.

Thus far, another global generic drug major Mylan is expected to file for a generic version of Advair/Seretide in the US by the third quarter of 2015 for a 2016 launch. Besides Cipla and Novartis, Mylan, Teva and Actavis are expected come out with the generic version of this drug.

Opportunities in ‘difficult to copy’ drugs:

According to a recent ‘RnR Market Research Report’, over 1,400 drugs with New Drug Delivery System (NDDS) have since been approved globally. This includes inhalation devices too.

The oral drugs contribute the largest share of the overall NDDS market with over 52 percent of the total pie. This segment is expected to attain a turnover of over US$90 billion by 2016 at a CAGR of 11 percent. The injectable new drug delivery market is expected to reach a turnover of over US $29billion by 2015, according to this report.

I have deliberated this subject in one of my earlier blog posts titled. “Moving Up The Generic Pharma Value Chain”.

Another high tech area – biosimilar drugs:

As the high priced biologic drugs of the innovator companies go off patent, large molecule biosimilar drugs, involving high technology, would emerge as another lucrative growth opportunity for the generic players having requisite wherewithal.

Recombinant vaccines, erythropoietin, recombinant insulin, monoclonal antibody, interferon alpha, granulocyte cell stimulating factor like products are now being manufactured by a number of domestic biotech companies. Some of the Indian companies that have already entered into the biosimilar segment are Dr. Reddy’s Laboratories (DRL), Lupin, Biocon, Panacea Biotech, Wockhardt, Glenmark, Emcure, Bharat Biotech, Serum Institute, Hetero, Intas and Reliance Life Sciences, besides others.

The ultimate objective of all these Indian companies is to get regulatory approval of their respective biosimilar products in the US and the EU either on their own or through collaborative initiatives.

Overall improvement in the quality of ANDA filings:

In the last few years, overall quality of ANDA filings of the domestic Indian pharma players has also improved significantly. Their regulatory filing schedules now include many complex molecules, injectibles, oral contraceptives, ophthalmic preparations, inhalers/other drug delivery systems and biosimilars, beside Para IV/FTFs. All these are now contributing a growing share in their new product initiatives for the regulated markets.

Conclusion:

In the largest pharma market of the world – the United States, global generic companies are increasingly facing cutthroat price competition with steep price erosion, registering mixed figures of business performance and growth.

However, a new trend is fast emerging. Even when global innovator companies are including increasing number of difficult to copy medicines in their product portfolio, some pharma players are reaping a rich harvest by moving up the value chain with the generic versions of those products, post patent expiry. These copycats offer much higher margin than non-differentiated generics.

Some Indian generic companies too have started focusing on building value added, difficult to manufacture, and technology intensive generic product portfolios in various therapy areas. DRL is reportedly all set to take its complex generic drug Fondaparinux sodium injection to Canada and two other emerging markets.

Those Indian pharma companies, which would be able to develop a robust product portfolio of complex generics and other differentiated formulations for the global market, would now be much better placed in positioning themselves significantly ahead of the rest, both in terms of top and the bottom line performance.

The myth, as epitomized in the good old saying, “Patent expiry matters less for difficult to copy drugs”, seems to be partly true in delaying entry of generics immediately after the end of the monopoly period, at least, for now. However, I reckon, this gap of delay would eventually get much reduced, if not eliminated altogether, as we move on. Armed with cutting edge technology Cipla has almost busted the myth, as it came close second to Novartis with the launch of a complex generic equivalent of Advair/Seretide in the EU and other markets.

Pharma majors of the country, such as, DRL, Cipla, Lupin and Biocon, to name a few, are taking great strides, setting examples for many others to emulate and excel in this area. The groundswell has already begun for a long haul global journey of the Indian pharma into the El Dorado of high tech generics fetching higher rewards.

By: Tapan J. Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.

 

Reaping rich harvest with less moaning and bagful of creative ideas from emerging Rural Markets of India

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About 72 percent of the population and 135 million households of India live in the rural areas of the country. Many of them are poor.

Definition of ‘Rural’:

Agencies of the Government of India like, National Council of Applied Economic (NCAER) and Insurance Regulatory and Development Agency (IRDA) have defined the terminology ‘rural’ as “villages with a population of less than 5000 with 75 percent population engaged in agriculture…”

Rural India is no longer an agrarian economy:

A recent study by ‘Credit Suisse’ indicates that rural India is no longer a pure agrarian economy, depending mostly on the quality of rain falls during monsoon season. This has been corroborated by the fact that the contribution of agriculture to the total GDP of rural India has come down from 50 percent, as registered during the turn of this century, to its current level of about 25 percent.

This transition of rural India from agriculture to industry and services, is now taking place at a much faster pace than ever before, as the rural economy is getting increasingly attuned to the national economic cycle, creating more and more non-agrarian jobs in those areas. Most of the incremental job creation is taking place in manufacturing, construction, retail and wholesale trade and also in the community services.

Currently, 55% of India’s GDP from manufacturing comes from rural India as the ‘Credit Suisse’ report highlights. As a result, since April 2000, per capita GDP in rural India has grown at a much faster pace than in urban India.

This welcoming change, in turn, is expected to play a key role in significantly improving the consumption of reasonably affordable healthcare, besides many other products and services, in the rural India.

Rural share of GDP growing faster:

Since last several years with various rural reform initiatives of the Government, the hinterlands of India have started growing faster than ever before.

A National Council of Applied Economic (NCAER) Research survey, indicating rural share of India’s GDP improved from 40 percent in 1980 to 54 percent in 2010, vindicates this point. At the same time, aggregate rural consumption (US$ Bn) increased from 94 in 1985 to 203 in 2005 and is expected to reach 350 in 2015. (Source: National Statistical Offices, UN, Euro Monitor International, Office of the Registrar General & Census Commissioner, India).

A new growth opportunity:

According to McKinsey Report, rural India currently accounts for 21 percent of the Indian Pharmaceutical Market (IPM). It is interesting to note from the NCAER report that both urban and rural India spend 5% of their total income on health.

Rural growth drivers:

McKinsey estimates that by 2015, upcoming smaller towns and the rural markets will contribute as much to the growth of IPM as the metros and top tier towns.

The following factors are expected to drive the growth of the pharmaceutical industry in the rural India:

  • Large patient base
  • Increasing overall income (over 1 percent of the total population coming above the poverty line every year)
  • Increasing number of middle class in rural areas
  • Disease pattern gradually shifting to chronic ailments
  • Improving healthcare infrastructure with increasing Government spend on the National Rural Health Mission (NRHM)
  • Rashtriya Swasthya Bima Yojana (RSBY), which is the National Health Insurance Scheme for Below Poverty Line (BPL) families, will provide health cover to increasing number of BPL households
  • New initiatives of the Department of Pharmaceuticals (DoP) like, “Janaushadhi”  scheme will provide low cost quality medicines to boost the uptake

Rural market size:

The rural markets contribute about 21 percent of U.S$ 12.5 billion pharmaceutical market in India (AIOCD-AWACS, February, 2012). As reported in ‘India Pharma 2015’ of McKinsey, by 2015 rural pharma market size is expected to reach U.S$ 4.8 billion from U.S$1.2 billion in 2005.

Currently, rural markets are dominated by ailments related to various types of infections. As stated above, this disease pattern is expected to change by the next decade to non-infectious chronic illnesses, like diabetes, cardiac, cancer, hypertension etc.

Increasing Pharmaceutical growth trend in the rural markets:

In 2011 the rural markets of India registered a growth of around 23 percent over the previous year. This decent pace of growth is expected to continue in the next decades.

MAT Dec 2011 (INR M)

MAT Dec 2011 (Saliency)

Growth %
Indian Pharma Market

538,028

100.00

14.92
CLASS I TOWNS

168,339

31.29

12.12
METROS

164,625

30.60

16.33
CLASS II TO VI

102,536

19.06

9.93
RURAL

102,528

19.06

23.19

(Source: IMS Town Class Data – Dec MAT 2011)

Moreover, McKinsey Report forecasts that rural markets will contribute around 27 percent of the total consumption of India by 2020 and by 2015, rural India will account for over 24 percent of the domestic pharmaceutical market from its current level of 21 percent.

Charting the uncharted frontier:

It has been reported that growth rate of the rural markets of many companies have more than doubled due to their rural marketing focus. Possibly as a testimony to this new business opportunity, one can now see:

1. Novartis with its “Arygoya Parivar” initiative is rolling out a tailor-made program for rural areas of seven states of India, to start with. They have developed special packs of essential medicines with special prices to reach out to the rural population. To create disease awareness within the target population and also for disease prevention and treatment, Novartis has deployed health educators for this project.

2. Sanofi has initiated a dedicated rural marketing initiative called ‘Prayas’.  The initiative is aimed at ‘bridging the diagnosis‐treatment gap through a structured continuing education program for rural doctors across India’.

The Company says, “through ‘Prayas’, specialists from semi‐urban areas will share latest medical knowledge and clinical experience with general practitioners based in smaller towns and villages in the interiors of India”. Their second strategy, reportedly, is for improving healthcare access by making quality medicines available at affordable prices for the rural patients.

3. Novo Nordisk is currently engaged in screening patients for diabetes in the rural areas of Goa with mobile clinics. This initiative is expected to create widespread awareness about diabetes and early detection of the disease, so as to prevent early onset of the disease related complications.

4. Eli Lilly developed a program along with the Self-Employed Women’s Association in Ahmedabad to educate and encourage rural patients suffering from tuberculosis to go for treatment.

5. Elder pharmaceuticals created a dedicated 750 strong rural marketing sales force called Elvista.

6. Cadila Pharma has set up a dedicated rural marketing arm called ‘Explora’.

7. Alembic Chemicals created a rural business unit called ‘Maxis’.

These are just a few illustrations and not an exhaustive list. However, the issue is whether the rural marketing initiative will continue to remain an experimental one to the pharmaceutical companies in India or will get translated into a decent long term strategic business move.

“The Fortune at the Bottom of the Pyramid”:

The iconic management guru C K Prahalad in his well-known book titled, “The Fortune at the Bottom of the Pyramid” wrote:

“If we stop thinking of the poor as victims or as a burden and start recognizing them as resilient and creative consumers, a whole new world of opportunity will open up.” I am not sure whether the above profound observation is encouraging the pharmaceutical companies to explore the rural India with the wings of courage, where majority of the Indian populations live and most of them are poor.

A ‘Pot of Gold’ in the rural markets?

Currently around 20 million middle class households live in over 6,00,000 villages of India. This is almost the same as the number of middle class households residing in urban India and holds the key to significant increase of healthcare spending in rural India.

Rural market-entry strategy:

Instead of transplanting the urban marketing strategy into rural India, some companies, as mentioned above, have taken the community-welfare route to make the rural population aware of particular disease segments like, tuberculosis, diabetes, cardiovascular, waterborne diseases etc. together with the treatments available for such ailments.

These value added marketing strategies offer benefits to both the patients and the company concerned. The local medical practitioners, in turn, are also benefited as they get increasing number of patients in their clinics through such disease awareness community program by the pharmaceutical companies.

Key challenges:

There are some key challenges for effective rural penetration by the Indian pharmaceutical industry, as follows:

• Inadequate basic healthcare infrastructure. Only 20 percent of total healthcare infrastructure of the country is in rural areas where over 72 percent population of the country lives. • Density of doctors per 10,000 populations in India is just 6. A large number of villages in India do not have any doctor. As per AC Nielson study, an average rural Indian has to travel about 6 km to visit a doctor. A Medical Representative will require traveling about 250 to 300 km every day just to meet about 10 doctors and 4 dealers. • Many villages are not well connected by proper all season roads. • Lack of appropriate supply chain network and logistics support.

Conclusion:

With increasing infrastructural support and tailor made innovative marketing strategies for rural India, simultaneously delivering both preventive and curative therapies under one umbrella, it may not be difficult for the Indian pharmaceutical companies to discover ‘The Fortune at the Bottom of the Pyramid’ – a win-win situation indeed for both the ‘haves’ and a vast majority of ‘have-nots’ living in an amazing country called India.

The name of the game is less moaning and a bagful of implementable creative ideas.

By: Tapan J Ray

Disclaimer: The views/opinions expressed in this article are entirely my own, written in my individual and personal capacity. I do not represent any other person or organization for this opinion.