India Research Opportunities, Price and Patent Problems: Interview with David Scondras
David Scondras, president of Search for a Cure in Boston, is an AIDS treatment activist who served for 10 years on the Boston City Council. Recently he was invited to India by philanthropists concerned about the rapidly growing HIV epidemic there and looking for opportunities to work together with people and organizations in the U.S. [See "A Visit to India: Drug Prices, Research, & Global Access" by David Scondras, AIDS Treatment News #311, January 22, 1999.]AIDS Treatment News: What can be done to bring modern, high-tech research to bear for testing potential treatments, both modern and traditional ones, to create proven treatments designed for the developing world (and which could also be used here to improve treatment combinations)?
Scondras: I spoke with leading public health officials and CEOs of major pharmaceutical firms in the state of Maharashtra (the largest state in India), and in the ICMR (Indian Council of Medical Research), the Indian equivalent of the U.S. National Institutes of Health, and with clinicians and researchers at large hospitals. They are compiling a list of potential treatments where they would like to see research collaboration between the United States and India.
Traditional Indian medicine uses a number of herbal drugs with immunomodulating and potentiating activities. Researchers picked one (a traditional and widely used immunorestorative Ayurvedic medicine) which raises T-cells, something like IL-2. Today this is the most often-prescribed medicine in India for HIV. Most often, nothing is prescribed.
ATN: It needs to be studied then to see if it works, even if only because it is being used.
Scondras: It is being used by a huge number of people. A pilot study and a small controlled trial have been done. [See SV Deshpande and others, "Effect of unique herbal formulation in Indian HIV patients: A pilot study," 12th World AIDS Conference, Geneva, June 28 - July 3, 1998 (abstract 42385). The controlled trial of the same traditional treatment (Reimun, code number PV-150896) has been completed and was presented at the 12th World AIDS Conference, although the published abstract (42358) only describes the uncontrolled pilot study and does not name the treatment.]
Indian researchers say why not do a head-to-head trial against IL-2? We are going to do an IL-2 trial in the United States; it will take us seven years, according to scientists who have designed it, to find out if IL-2 (given in addition to antiretroviral therapy) does or does not delay the onset of opportunistic infections and mortality. And there are serious questions whether any such study can be large enough to get a clear answer [because the rate of illness and death is so low in those who would be eligible for the trial and who have access to modern treatments].
But in India researchers are saying why not compare IL-2 with the traditional T-cell booster? You will find out very quickly if you are avoiding opportunistic infections. The standard of care in India is Ayurvedic medicines, if anything at all. Availability of even prophylactic medications is episodic at best or non existent.
People in India are saying that since there is no way for most people to get antiretrovirals, we have to know whether or not this less expensive way of managing the illness works--that this is an emergency, and there needs to be an emergency trial to find out, and it could be done in India very quickly. You could have a definitive answer within a year. Seven years vs. one year means many millions of lives. Collaboration would be in both countries' interest. There is also the possibility of using antiretrovirals made by Indian firms and trying out IL-2 with these, and interruption of therapy models to see if there is any benefit from a short course of antiretrovirals with interruptions and immunopotentiating agents. We simply must find out whether what is available can be used to benefit people.
Activists in the U.S. will need to get the FDA and the NIH to help construct clinical trials done in India, working together with the local doctors there so that if the drug works, the results can be submitted successfully when the drug comes to the FDA for U.S. approval. Otherwise, companies will not want to put up the money to do the trials. I have talked with several top U.S. clinicians who said they would be willing to play an active role, such as monitoring or being a principal investigator in India.
The NIH, FDA, and other U.S. agencies are already involved in other projects in or near India. For example, Robert Bollinger of the NIH is doing vaccine work in Puna, near Mumbai. So there's no reason there cannot be a monitoring structure which allows the results of studies there to be submitted for drug approval in the U.S.--especially if trial arms are being run in both countries.
Another example of trials Indian researchers and officials want to do is microbicides for prevention; a proven microbicide would provide a means for women to protect themselves from HIV infection. Even though we do not know at this time how effective microbicides might be, we do know that several are now being tested in the U.S. in phase I trials.
In Mumbai (Bombay) you could do an efficacy trial of a microbicide and have definitive data in less than a year. But in the U.S., such a trial would take years, be exorbitantly expensive, and might not conclude--because of the lower transmission rates, access to antiretrovirals here, greater availability of condoms, etc., and also because the clade of the virus may be a factor (the female-to-male transmission rate is much higher in India than in the U.S.)
India also needs trials of less expensive antiretroviral regimens. The Atlantic study, presented in Chicago at the most recent Retroviruses conference, indicated that regimens with d4T, ddI, and either 3TC or nevirapine could reduce viral load in some patients about as much as a standard protease-inhibitor regimen, at least at 24 weeks. Additional studies of this type makes sense--especially since the versions made in India by CIPLA, a local reputable pharmaceutical firm, are much less expensive than the U.S. counterparts, and these drugs are already less expensive than the protease-containing regimens.
And there is discussion in India of intermittent therapy, and of heavy antiretroviral treatment followed by a maintenance combination like ddI and hydroxyurea. Each of these efforts is clearly directed at trying to find some regimen inexpensive enough for India, which none of the present regimens are. But if successful, this research would also help patients everywhere, by providing well-tested options which may reduce side effects as well as expense.
ATN: What can be done to get such trials underway?
Scondras: There is a $40 million contract now being processed between the U.S. National Institutes of Health, the U.S. Agency for International Development, and the ICMR in India. This contract, astonishingly, has not one nickel for treatment. It is entirely a prevention contract, where "prevention" does not include even vaccines or microbicides.
Many of the people I spoke with noted that without some targeted research, most people with HIV in the world, and in India, will get palliative care at best, but not anything substantive--and this is unacceptable. As a result, physicians have compiled lists of trials they want to see conducted collaboratively, which would be a win-win situation for India, the developing world, the United States, and other developed countries. Dr. Charles Gardner, the scientific advisor to the American Ambassador to India, indicated to me that there was interest in pushing for some clinical trials that both the American and Indian officials would like to see developed.
ATN: What are the main practical problems that doctors in India now face?
Scondras: The first thing doctors and everyone else tell me is that lack of affordable drugs is their biggest single problem. Of course they recognize that other problems are also urgent, for example, lack of clean water. And everyone agrees that in the developing world, HIV and tuberculosis is like a hyphenated word; tuberculosis is very common in persons with HIV infection.
But the clinicians say that lack of medications is number one--for tuberculosis and for malaria, as well as for HIV. In fact the single most important reason for MDR tuberculosis (multi-drug resistant), a killer that could haunt the world for may years, is our shortsightedness in not providing consistent regimens powerful enough to knock out TB. There has been a tendency to say that lack of compliance is a problem, when on the ground it is clear, as people come for their medicines and there aren't any, that lack of medicine is the key problem.
Because of its infrastructure, India is in a unique position to help in worldwide access to medications. It can manufacture drugs probably cheaper than any place in the world. It has pharmaceutical companies, laboratories, well-trained physicians, scientists, industry, transportation, and so forth, and has many economic and political relationships with developing countries.
ATN: U.S. pharmaceutical companies say India does not respect their patents.
Scondras: India's ability to produce cheap medicines for the world is the result of its refusal historically to accept product patents on pharmaceuticals. The Indian government does recognize patents on the process of manufacturing a drug, but felt that the end result, the drug itself, should never be restricted by a patent. In the Indian system, if a company can find a way to make a protease inhibitor by a different method, there is no reason they cannot have a patent for that version of it.
This policy creates lots of competition around every drug in India, and in the development of manufacturing methods, and the consequence is that prices are enormously cheap. But unfortunately, under the terms of the GATT treaty, India has only a few years to change its patent system to recognize product patents; and in the interim, it has to give monopoly marketing rights to certain patented drugs. So the ability to keep drugs cheap by not patenting the end product, but rather the process, is going to be taken away from India.
The only alternative which would permit local competition to bring down prices of drugs still under patent is compulsory licensing, which means that in response to a public emergency, the government of a country sets the terms for licensing a particular patent [see AIDS Treatment News November 20, 1998, March 5, 1999, and April 16, 1999; these can be found at our back-issue site, www.aids.org/atn/ --search for 'compulsory licensing'.]. But the U.S. government, acting on behalf of big pharmaceutical companies, has made it very clear it will do what it can to put an end to compulsory licensing of pharmaceuticals--even though the U.S. uses compulsory licensing itself, for lesser emergencies such as broadcasting of music, sports events, and other entertainment. The three avenues where India could help to provide affordable medicines to the world--process instead of product pharmaceutical patents, compulsory licensing, and parallel importing--are the three being closed down by the United States, legally or extra-legally.
Since the major pharmaceutical firms don't sell many drugs in India (the whole developing world accounts for less that 3.5% of the sale of medicines, and India is a fraction of that), it really makes no financial difference if India makes copycat drugs or not. There is no way to get those copycats into the European or U.S. markets where drug purchasing is done by governments (or in the U.S. by big insurance companies and HMOs, not noted for their late night trips to illegal pushers of cheap contraband). In fact, allowing India to produce drugs under a limited license voluntarily granted by the patent owner, along with company oversight, would produce some money for the company which it does not get now from the developing world, create goodwill, help save the world from illnesses that are treatable, and benefit many people. If done right, there need not be any downside at all to American or European industry.
ATN: How can people help work on this issue?
Scondras: One way is to contact groups like the Health Gap Coalition, which was set up for this purpose; its Web site is www.healthgap.org. For technical background, see Ralph Nader's Consumer Project on Technology pages on intellectual property and health, for example on the recent U.S.-South Africa dispute on these issues, http://www.cptech.org/ip/health/sa/. And there is much discussion of these issues on the Treatment Access forum in Geneva, http://www.fdp.org/forums.html (click 'list of messages'); this online discussion started in conjunction with the 12th World AIDS Conference in Geneva last summer.
Also, call or write your Congressperson and tell their office that you resent the fact that the U.S. Trade Representative and other branches of government are trying to intimidate and harass South Africa, Thailand, and other developing countries, to not use the rights that they have under international treaties to make medicines that people can afford, and need to stay alive. That is outrageous, especially when the U.S. itself is using compulsory licensing all the time, for entertainment, computer technology, and other areas that are far from a life-and-death situation. And send a copy of your letter to the Health Gap Coalition.
Also contact your Congressperson (the Congressional Switchboard is 202-224-3121) to support Jesse Jackson Jr.'s Hope for Africa Act, HR772 (not HR434, the so-called African Growth and Opportunity Act). And check the Web sites above for other alerts around these issues.
This is a genuine peoples' movement that is certainly coming from the ground up. It's amazing.
