April 21, 2011

HIV Drugs and accessibility



HELP IN THE HOUR OF NEED

The Indian Government needs to extend its help to support HIV patients in minimising therapy costs, which in turn will provide an opportunity for domestic drug manufacturers. Usha Sharmaanalyses the current demand and availability of HIV drugs in India.

Before we begin to discuss the HIV drug market in India, it is important that we should know the population pool infected with HIV across the globe. HIV anti-retroviral (ARV) sales across the seven major markets of the world (ie. US, Japan, France, Germany, Spain, Italy and the UK) accounted for around $11.8 billion. However, it is possible that in the coming year, emerging markets will also have some foothold in this segment. The governments of India, Brazil and other countries are under pressure due to the alarming rates at which the disease is spreading and the resistance of the disease to first line of treatment.

This may provide a business opportunity to big pharma companies to foray into these markets through voluntary licenses and agreements with domestic manufacturers. This is present in both regulated and semi-regulated markets. Globally, HIV has become a major cause for concern. Each year there has been a large number of HIV-related deaths across regions where the percentage of low- to middle income groups is higher. However as per UNAIDS statistics, the number of people newly infected people with HIV decreased from 3.1 million in 2001 to 2.6 million in 2009.
"If these decisions are correct, then it’s good for India’s patent law, which will be seen as preventing routine extensions/ improvements from being patented and aims to work in favour of public health by only granting patents to drugs that are genuinely innovative"
Hitesh Gajaria
Executive Director
KPMG


In India, there are around 30 to 35 companies operating in the HIV market. This includes both domestic as well as multinational companies (MNCs). The country had around 2.4 million people HIV-infected people in 2009, as per a report published by National AIDS Control Organisation (NACO), with a 15 to 49 years prevalence rate of 0.31 per cent contributing to 83 per cent of the total HIV population.


The current market size of HIV drugs in India is around ` 151 crore, and growing at around 11 per cent over the previous year. Four states, namely Andhra Pradesh, Maharashtra, Karnataka and Tamil Nadu contribute 0.5 million, 0.42 million, 0.25 million and 0.15 million respectively and account for nearly 55 per cent of those infected with HIV in the country.

Hitesh Gajaria, Executive Director, KPMG summarises India's market value in this segment. He says, “It is estimated that the ARV segment which is the most common/effective HIV treatment, is likely to grow at a CAGR of 22 per cent between FY 2010-12 and reach a value of ` 750 crore. The market has been growing steadily at a rate of 12-15 per cent from FY 2007–2010.”
RegionAdults and children living with HIV (in million)Adults and Children newly infected with HIV (in million)AIDS related deaths among adults and children (in million)Percentage Adult prevalence (15-49 years)
Sub Saharan Africa22.501.81.35.0
South Asia and South East Asia4.100.270.260.3
North America1.500.070.020.5
Eastern Europe and Central Asia1.400.130.070.8
Central and South America1.400.090.050.5
Western and Central Europe0.820.030.0080.2
East Asia0.770.080.030.1
Middle East and North Africa0.460.070.020.2
Caribbean0.240.010.011.0
Oceania0.050.0040.0010.3
Total33.32.61.80.8
Source: UNAIDS Regional HIV and AIDS statistics, 2009
India is the largest supplier of generic ARVs to low- and middle-income countries. Thailand and South Africa also produce a significant amount of generic drugs. Many African nations — such as Zambia, Ghana, Tanzania, Uganda and Zimbabwe have also developed local anti-AIDS drug manufacturing facilities. Domestic companies that manufacture the HIV drug include Cipla, FDC, Torrent, Hetero, Sun Pharma, Lupin, Ranbaxy, Zydus Cadila, Natco, Alkem and GSK, Ranbaxy, Emcure and Aurobindo.


MNCs operating out of India include Roche and Mylan (previously Matrix Lab). Recently, ViiV Healthcare (a 85:15 Joint Venture (JV)between GSK and Pfizer, specialised in HIV medicine) has been in the news seeking a partner to launch its patented HIV drugs in the Indian market. Indian generic drug manufacturing companies such as Aurobindo Pharma, Ranbaxy, Hetero, Cipla and Mylan are likely to leverage the opportunity that will arise when most of these drugs lose their patent exclusivity.


Cipla, especially, is establishing a strong presence in the segment with the company's total ARV formulation sales totalling ` 550 crore and has reported a growth of over 40 per cent for the nine-month period ended December 2010. Multinationals that have a foothold in the segment include GlaxoSmithKline, Pfizer, Merck BMS, Gilead and Abbott.

In 2001, Cipla, announced that it would sell a generic version of the triple-therapy ARV (stavudine+ lamivudine + nevirapine) drug. Generic ARVs are available under many integrated programmes such as PEPFAR - the President's Emergency Plan for AIDS Relief.

It is, however, difficult to put a concrete number to the brands/generics available in the segment. At present in the Indian market there are about 30 ARV drugs available. But Roche’s Fuzeon (enfuvirtide), Boehringer Ingelheim’s Aptivus (tipranavir) and GlaxoSmithKline’s Lexiva are not available in India from 2010. In terms of the number of ARV products, Cipla, Emcure and Hetero have a larger number of products in the market.
The Indian HIV market is dominated by generic products. In 2009, Cipla’s Viraday tenofovir/ emtricitabine/ efavirenz (a generic formulation of Gilead’s/Bristol-Myers Squibb’s Atripla) was the highest selling product with sales of $6.8 million (MIDAS sales data, IMS Health, April 2010). As per the data, Cipla’s Triomune (stavudine/ lamivudine/ nevirapine) was the best selling product in terms of volume and its Duovir-N (lamivudine /zidovudine/ nevirapine) was next. This is in line with the NACO treatment guidelines, which recommend using both these regimens (as fixed dose combinations) in first-line.

In January 2011, India rejected the patent application for the drug Atazanavir Bisulphate, filed by Bristol-Myers Squibb (BMS), and a combination drug Lopinavir/Ritonavir filed by Abbott. Both these drugs are recommended as second-line treatment for HIV patients after the failure or resistance to first line drugs. In September 2009 also India had rejected patent applications for Tenofovir and Darunavir filed by US drug companies, Gilead Sciences and Tibotec Pharmaceuticals. Darunavir is a second line drug for HIV patients, while Tenofovir can be used for both first and second line treatments. With many patients showing resistance to first line drugs, and second line drugs being much more expensive, it limits access to a small section of the population.
"Besides keeping HIV drugs affordable at present, these patent rejections will also encourage more generic suppliers to enter in this segment, further dropping the price of treatment, and thus, help increase its accessibility to patients"
Bibhuti Bhusan Kar
Programme Manager
South Asia and Middle East Healthcare
Frost & Sullivan


Bibhuti Bhusan Kar, Programme Manager, South Asia and Middle East, Healthcare — Pharmaceuticals and Biotechnology, Frost and Sullivan predicts, “These moves by the Indian Government is definitely positive as far as Indian pharma companies are concerned given the fact that affordable HIV treatment across the globe is dependent on Indian pharma companies.”

There is also increased effort on the part of voluntary organisations such as Clinton Foundation, Bill and Melinda Gates Foundation, Médecins Sans Frontières (MSF), UNITAID, PEPFAR etc to increase the accessibility to HIV drugs in countries with a higher percentage of low- and mid-income groups. This can only be done with generic medicines.
"Though this is a patent law-related issue, unfortunately it has been hyped up as a ‘major victory for public health and access to affordable treatment" Tapan Ray
Director General
Organisation of Pharmaceutical Producers of India
Tapan Ray, Director General, Organisation of Pharmaceutical Producers of India (OPPI) emphasised, “Recently two key HIV/AIDS medicines namely, lopinavir/ritonavir and atazanavir bisulphate were not granted patents by the Indian Patent Office with the reason cited that they 'lacked inventive ingenuity'. Though, this is a patent law-related issue, unfortunately it has been hyped up as a ‘major victory for public health and access to affordable treatment’.”

Gajaria agrees with his industry colleague and explains that, “The patent for the drug atazanavir bisulphate filed by Bristol-Myers Squibb was rejected because it 'lacked inventive ingenuity', while Abbott's patent application for lopinavir/ritonavir (Kaletra) was turned down as it did not involve an 'inventive step'.

Before 2006, there was no generic production of lopinavir/ritonavir, and Abbott was able to charge close to $6,000 per person per year in some developing countries. Today, generic companies like Hetero and Ranbaxy have brought the prices down substantially to $440 per patient per year. Generic companies including Cipla and Hetero are major suppliers of these drugs to developing countries like South Africa. The rejection of these patents indicates that there could be undisrupted supply from India for AIDS programmes in developing countries, some of which have even issued compulsory licenses (Ecuador, Thailand) that waive their local patent barriers to obtain generic drugs from here.”

He adds, “This decision also provides motivation for producers to enter the market and lower the price further. If these decisions are correct then it’s good for India’s patent law, which will be seen as preventing routine extensions/ improvements from being patented and aims to work in favour of public health by only granting patents for drugs that are genuinely innovative.”

The move by the Indian government to reject the patent application is an encouraging step to protect the public health given the fact. Indian manufacturers not only supply drugs in India, which is home to around 2.4 million HIV patients, but is also a major supplier to the Sub Saharan Africa region - home to 22.5 million HIV patients struggling with an accessibility problem of slightly more than 35 per cent for HIV medicines.
"The decision provides access to these second-line treatment drugs at a low cost for NGO’s and other public health organisations (NACO, etc), which in turn provides another opportunity to the pharma companies focusing on ARVs to supply these drugs to AIDS programmes in developing countries" Ramaraju Nallaparaju
Senior Consultant
Datamonitor Healthcare Consulting
Ramaraju Nallaparaju, Senior Consultant, Datamonitor Healthcare Consulting simplifies this view and explains the stand of the Indian Patent Office saying, “The rejection of the patents for these drugs has to be taken from the perspective that the Indian Patent Law does not encourage or allow granting of patents for minor improvements in products and grants it only to those which are highly innovative. The decision provides access to these second line treatment drugs at a low cost to NGO’s and other public health organisations (NACO, etc), which in turn provides another opportunity to pharma companies focusing on ARVs to supply these drugs to AIDS programmes in developing countries.”
Name of the states / UTPopulation living with HIV infection (In million)Percent of total HIV population in India
Andhra Pradesh, Maharashtra, Karnataka and Tamil Nadu0.1355
West Bengal, Gujarat, Bihar, Uttar Pradesh and MP0.6226
Rajasthan, Orissa, Punjab, Kerala and Chhatisgarh0.2812
Other states and UT0.187
Total2.4100
Source: NACO, 2009
Kar highlights, “Besides keeping HIV drugs affordable at present, these patent rejections will also encourage more generic suppliers to enter in this segment, further dropping the price of treatment, and thus help increase its accessibility to patients. This will encourage more number of patients to be put on the second line treatment after the failure of first line drugs, especially through the government run AIDS control programmes, which at present have a large number of patients on second line and 0.3 million patients on first line drugs.

The patent applications that were rejected on grounds that they did not meet the criteria in section 3(d) of the Indian Patent Act that prohibits patenting a product that follows the process popularly called 'evergreening' of known medicines. 'Evergreening is a process of making minor modifications in the existing drug without a significant improvement in its therapeutic effects. This tactic is practised by pharma companies to extend the patent life of a branded drug, and thus acts as an entry barrier for generic manufactures to market the drug.

The need of the hour is that ARVs are accessible to even the poor at affordable prices. India is one of the countries which has capabilities to provide the second line of treatment to developing countries at reasonable rates.

Kar shares his concern, “To avoid these situations, which may result in complications in the future, the Indian Government. should support/ encourage the Indian pharma industry to enhance its R&D capabilities for ARV developments and immediate attention should be given to providing tax relief, grants for R&D, incentives and so on. Favourable Government policies to encourage building world-class R&D infrastructure would help the Indian pharma industry to be competitive in the long run.

Gajaria suggests, “The Government can also facilitate an open dialogue between pharma companies and NGOs who help the suffering, poor and needy persons with a view to ensuring the availability of pharma therapies against AIDS at affordable rates.”


- Source: Express Pharma, April 2011