The Role of Generic Drugs in the Fight against AIDS

Yusuf Hamied (Speech at the Vatican, 2004)

Friends,

It is a unique privilege and a humbling experience to address this distinguished gathering at the Vatican.  All the suffering and death from war, famine and natural disasters in the 20th century will be eclipsed by HIV/AIDS in the 21st century.  The HIV/AIDS virus has already killed 22 million people worldwide during the past 20 years.  It eats deep into our lives and spares nobody.  It transcends all Nationalities, Race, Religion, Social and Political boundaries.  It is the first disease ever to be labelled a global killer by the UN Security Council.  It is a grave existing danger with catastrophic consequences for the human race.  We need the will and courage to fight the crisis with all the energy and resources at our command. With so much God given life at stake, this is one battle the human race cannot afford to lose.

Today’s meeting helps to restore our faith and hope in what many of us are endeavoring to do.  It is sad that every day over 8,000 people are dying of AIDS.  At least 30 million are afflicted in Sub-Saharan Africa and 45 millions Worldwide.  It is estimated that this figure will reach 65 million by the year 2010, of which over 25 million will be in India alone. Russia, South East Asia and China also stand on the brink of a widespread epidemic. Of the 16,000 children born daily in Africa, 1600 are HIV positive.  The tragedy facing us is that the medicines that are available which can extend and improve the quality of life are not being used. The Vatican has made many positive statements regarding the issue of HIV/AIDS.  In his Lent message earlier this year, the Pope referring to this said, “ Humanity cannot close its eyes in the face of such a dramatic situation”.

I represent the 3rd World Generic Pharma Industry.  This Industry has recently been chastised, condemned for its copycat drugs, so-called piracy and also safety and quality of the drugs they produce particularly in relationship to the anti-AIDS fixed dose combination drugs.

In order to comprehend the significance of the role played by my company Cipla, I must give you a brief historical background. This has its origin in 1939, when Mahatma Gandhi visited Cipla in Bombay and requested us to produce vital medicines for the Indo-British war effort.  At that time, the importation of drugs into India from Europe had totally stopped. At a very early stage, we learnt the importance of self-reliance and self-sufficiency.

When I joined the pharma industry in 1960, I soon realized that every major drug we
wanted to manufacture was covered by patents – a monopoly granted to the innovator for 20 years.  The MNC’s controlled 85% of the domestic market and exports of drugs from India were negligible.  Britain had changed its patent laws in 1949 but we in India were still fettered to the archaic British Patent Act of 1911.

National minded Indians fought for 12 years to amend the prevailing draconic patent laws. We were successful in 1972.  The Indian Patent Act, 1970, gave the pharma industry the legal freedom to manufacture and market almost any drug required in our country, which was available internationally. In the two vital areas of Health and Food, there could be no monopoly on the end product, only the production process could be patented for a period of 7 years. It was the beginning of a Golden Age for the indigenous pharma industry.  Today, 32 years later, over 80% of the Indian pharma market of US$ 4 billion and virtually all the pharma exports of US$ 3 billion are controlled by Indian companies.  No longer is the Indian pharma label considered inferior. It stands for quality, trust and respectability. Many Indian Pharma Companies now have international Regulatory Approvals and have become major suppliers of bulk actives and formulations.  Cipla already has a Global commitment, supplying medicines to over 140 countries worldwide.

I would now like to talk specifically about HIV/AIDS. In the late 80’s, India became aware of the AIDS virus.  In 1991 we were approached by the Indian Government specifically to product AZT, the only known mono-therapy drug at that time to combat AIDS.  We took up the challenge and in 1993 introduced AZT in the Indian market for the equivalent of US$ 2 per day as against the then prevailing international price in excess of US$ 10 per day. In spite of this, the price was beyond the reach of most Indians.  Our sales were so dismal that by the end of 1993 we stopped making AZT and lost all interest in the future development of Anti-AIDS drugs.

In 1997, we came across the HAART (Highly Active Anti-Retroviral Therapy) Medical Report, which rekindled and revived our interest in the AIDS Issue.  It claimed that a cocktail of 3 drugs was effective in controlling and managing HIV/AIDS.  No longer being HIV positive was considered as a death sentence but rather as a chronic ailment.  The 3-drug combination could vary but essentially consisted of a minimum of 6 pills to be taken daily.  At the time, these were only produced individually by different MNC’s and the combined price was around US$ 10,000 to 15000 per patient per year. This was simply unaffordable particularly in the poor Sub-Saharan countries where AIDS was rampant.

We took up the challenge to produce a range of anti-retroviral drugs and were successful by the year 2000. Our criteria for the selection of the best-suited triple drug cocktail was based on Quality, Safety, Efficacy, Affordability and Sustainability of supply.  We limited our drug choice to taking one drug from the group Zidovudine, Stavudine or Didanosine, one drug either Nevirapine or Efavirenz and finally
Lamivudine.  We then worked out various combinations that fitted into all our criteria.

We decided that under the circumstances the best cocktail consisted of Stavudine, Nevirapine and Lamivudine.   We went beyond what was then available by any one MNC.  The three drugs in question were separately being produced by three different companies.  They could not combine them into one tablet, but legally we in India could. Cipla’s product Triomune was born. Along with Triomune, we developed other fixed dose combinations.  Of importance being Duovir-N containing Zidovudine, Lamivudine and Nevirapine in one tablet.
In September 2000, at the European Union in front of a World audience we offered our Triomune to the International community at US$ 800 per patient per year as against the then prevailing price of over $ 10,000.  We also offered totally free, technology to any 3rd world government wanting to produce their own ARV drugs. Subsequently, we also offered to supply free worldwide, the single dose drug Nevirapine capable of stopping the transmission of HIV from Mother to Child.  Surprisingly, the World watched silently and there was no response.

In February 2001, we took another bold humanitarian step and announced a major price reduction for our leading first line therapy drug cocktail Triomune at below US$ 1 per patient per day, the taking of two pills per day one in the morning and one at night as opposed to 6 pills and more per day. This assured dosage compliance and with it minimal drug resistance.  With this price of treatment less than a dollar a day, awareness to the problem of HIV/AIDS became a worldwide phenomenon and it opened up the much larger subject of access to medicines at affordable prices.  It dawned on one and all that anti-AIDS drugs were not only available from generic companies, but also affordable. The absolute power of patents and drug monopoly was clearly exposed.

In mid-2001, it was said that Cipla was not qualified by WHO, who were the world’s foremost regulatory body for approvals.  At that time, no Generic company had ever been approved for drugs to combat HIV/AIDS.  We applied for approval and within a relatively short period of time a number of our anti-retroviral drugs and drugs for opportunistic diseases arising out of HIV/AIDS were qualified by WHO as also three of our factories producing these drugs after due audit and physical inspection.  Initially, these were all single ingredient drugs and the only fixed dose combination drug that was qualified was that of Zidovudine plus Lamivudine, called Duovir.  We then applied for approval of our Triomune, fulfilling all the criteria laid down by WHO for approval of fixed dose combinations.

It took a further period of time for WHO to qualify Triomune, again reflective of the thoroughness of the approval system.  It was a major break-through in the fight against AIDS.  This was announced on World AIDS Day – 1st December 2003 by WHO.   Other Generic companies were also approved for their ARV’s.  WHO also announced that such fixed dose ARV combinations opened the door to 3 by 5 – treating 3 million HIV positive persons by 2005.  We have informed WHO that we can undertake manufacture of one-third of this commitment and with proper inputs even go up to two-thirds. No problems are anticipated in the production of 4 million or even more ARV tablets daily within our existing capacity.

The main bottleneck in future supplies on a sustainable basis are predictability of demand and with it the manufacture and availability of the active pharmaceutical ingredients (API’s) that go into the final products.  I would like to be open and transparent and apprise you of this major hurdle in some detail.  None of the API’s used as anti-AIDS drugs are simple molecules. By and large their synthesis is complicated. None of them are used in low dosage.  If we have to manufacture

Triomune for one million people annually, we need to have 30 tons Stavudine, 110 tons Lamivudine and 146 tons Nevirapine.  It is for this reason that we decided at an early stage not to use any Protease Inhibitors in our fixed dose combinations against HIV/AIDS.  If we did use Nelfinavir we would need 900 tons for one million patients per year.  No one company in the World, whether Generic or an MNC can today produce API’s required for HIV/AIDS at the levels required.  We therefore have to organize supplies using a collective format i.e. manufacture ourselves, purchase from other Generic companies within India and procure intermediates and API’s from abroad, mainly from China and Korea.

The investment to produce API’s on the scale required is huge and I sincerely believe that if International funds are forthcoming to combat HIV/AIDS, the prime emphasis should be in investment for the manufacture of API’s. One very encouraging factor is that over the past few years, the Generic Industry particularly in China and India has dramatically improved the technology to produce most of the APIs required for HIV/AIDS. This can be seen from the sharp fall in prices of the API’s in the 3rd world.  From a level of $ 3000/kg, the price of Zidovudine is today down to below $ 500/kg. Similarly, Lamivudine is today below  $450 per kg as against US$ 7000 a few years ago.  Nevirapine from being available at $ 5000 per kg is today below $ 400/kg.  With the level of current API prices we have been able to further reduce the prices of the finished dosage forms and for example are today offering our Triomune at around US$ 200 per patient per year and with confirmed predictability, irrevocable orders and guaranteed payment the price can be even lower.

The Generic industry believed that they had achieved a major breakthrough when
President Bush in his State of the Union address in January 2003 said and I quote “On the Continent of Africa, nearly 30 million people have AIDS including 3 Million children.  There are countries in Africa where one-third of the population carry the infection, 4 Million require immediate treatment.  Only 50,000 are receiving the
medicines they need.  In an age of miraculous medicines, no person should hear – “You’ve got AIDS.  We can’t help you.  Go home and die”.   AIDS can be prevented.
Anti-retroviral drugs can extend life for many years.  And the cost of those drugs has dropped from $ 12000 a year to under $ 300, which places a tremendous possibility within our grasp.  Seldom has history offered a greater opportunity to do so much for so many”.  He went on to commit $ 15 Billion over 5 years to stem the growing AIDS pandemic.

In spite of promises, initiatives and dialogues, virtually nothing has happened since then. The Global Fund for HIV/AIDS, TB and Malaria was created a few years ago.  The Work Bank promised to take an initiative and MSF, UNICEF and many NGO’s became more active.  Overall, there has been no real forward movement.  The WHO qualification system for decades regarded as the best anywhere, has been attacked.

The Generic industry producing fixed dose combinations has also been maligned with claims including poor quality and efficacy.  These delays and frivolous accusations against approved, affordable anti-retroviral drugs, is totally uncalled for.
For the past few years, we have been supplying our ARV’s to 90 countries and specifically our Triomune to 43 countries with total acceptability.

It is surprising that while the so-called educated, civilized world indulges in empty rhetoric and agonizes over IPR, moral issues, diminishing profits, the AIDS Genocide spreads unabated, when appropriate treatment is available but not being used. I would like to stress most emphatically that we all have a moral obligation to fight this tragic disease.  For the sake of the AIDS afflicted people and their families we must enhance awareness and provide counselling to ensure care, proper treatment, comfort, support and remove the stigma against people who are HIV positive. We must work together to minimize the social and economic impact on the individual, his family and society.  We must further our efforts to find newer effective therapies, preventive medications, vaccines and hopefully one day even a cure.  We must redefine the present and future roles of governments, NGO’s and everyone involved in policy making.

One of the greatest predictable tragedies the world will witness will begin when WTO’s TRIPS becomes law in India on 1st January 2005.  India will revert back to its pre-1972 era of monopoly.  It will deprive the poor of India and the 3rd world of affordable medicines they need to survive. Again, we will be dividing the world between those who can afford life saving drugs and those who cannot – a systematic denial to the 3 billion in the poorer nations to help their own populations.

I quote from the Editorial of the 7th April 2004, issue of the Herald Tribune, “The US needs to allow some of its AIDS fund to be spent on generic combination drugs that have proven so effective.  Unfortunately officials are raising argument after argument against the combination pills – are not US FDA approved, they violate American patent laws, even if safe and effective.  Yet another objection, we don’t know if the combination therapy will provide lasting AIDS relief.  But the combination pills are simply standard therapies in convenient form.  Any therapy may later be superseded, we have to save lives with the best treatments available now”.

To this I would like to add that we all want a world where healthcare is provided to one and all, where every citizen can dream of a decent quality of life, particularly those afflicted with HIV/AIDS.  Cipla and like-minded generic drug companies are committed to the fulfilment of this dream.  We will cooperate with one and all in this Herculean task.  I quote a 1981 WHO statement of Indira Gandhi, late Prime Minister of India, “ My idea of a better ordered world is one in which medical discoveries would be free of patents and there would be no profiteering from life or death”.  In conclusion, it is appropriate to quote Nelson Mandela, who recently said, “AIDS is no longer a disease, it is a Human Rights issue”.

Thank you.

Dr. Y. K. Hamied, Cipla at the Vatican, May 7th 2004