AIDS Trestment News
Neuropathy: Call for Information on Voltaren Emulgel (Topical Diclofenac Sodium)by John S. James
We would like to hear (1) of others' experience with Emulgel, or other brands of topical diclofenac sodium, for relieving neuropathy; (2) any information about obtaining it in the U.S.; and (3) experience with topical use of other anti-inflammatory drugs for treating neuropathy. Contact us at AIDS Treatment News, either by email at firstname.lastname@example.org, by phone at 800-TREAT-1-2 or 415-255-0588, or by mail at P.O. Box 411256, San Francisco, CA 94141.
India Research Opportunities, Price and Patent Problems
Interview with David Scondrasby John S. James
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, www.hivnet.ch:8000/treatment-access (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.
Salvage Therapy Workshop: More Web Reports
And as we noted in our last issue, other reports of the conference are at:
FDA Public Meeting on Dietary Supplement Regulation, Oakland, CA, July 20
Register by July 14; Written Comment Deadline August 20by John S. James
Importance -- and Comment
We need to follow this issue because there is some backlash against the Dietary Supplement Health and Education Act (DSHEA), a law designed largely by the dietary supplements industry which limits the FDA's ability to regulate many health products. Without this law, dozens if not hundreds of products now on the shelves of health-food stores and drugstores would probably be banned, pending drug-type clinical trials to prove their safety and efficacy -- trials which will never be done because the products are low-cost and largely unpatentable. Consumer protectionists and pharmaceutical companies both have interests in restricting public access, for different reasons. The backlash is likely to develop into an important public debate on health, freedom, and regulation in U.S. society.
Our concern is that patients with serious illnesses not be left to pay the full price for the dysfunctional drug-development system, which seldom researches natural or low-cost treatments, strongly preferring expensive proprietary chemicals even when they are more dangerous. Until truly effective treatments are developed, people need a wide choice of safe and plausible options so that they can explore to see what may work for them.
We suggest distinguishing between empowerment-positive regulations (such as accurate labeling, so that customers know what they are buying), empowerment-negative regulations (such as banning a substance completely), and empowerment-neutral regulations (such as prohibiting claims). Our view is that empowerment-negative regulations should be avoided unless they are clearly necessary. Empowerment-neutral regulations can be considered to reduce overall risk by restricting mass marketing and promotion of unproven remedies, without denying treatment options to the individuals who want to try them.
Focus of the Meetings and Written Comments
The FDA has published seven questions and asked that public comments focus on one or more of those:
"Agenda and Goals
"To help focus comments ... FDA requests that oral and written input regarding an overall strategy for achieving effective regulation of dietary supplements address the following questions:
"1. In addition to ensuring consumer access to safe dietary supplements that are truthfully and not misleadingly labeled, are there other objectives that an overall dietary supplement strategy should include?
"2. Are the criteria for prioritizing the tasks within the supplement strategy appropriate? Which specific tasks should FDA undertake first?
"3. What factors should FDA consider in determining how best to implement a task (i.e., use of regulations, guidance, etc.)?
"4. What tasks should be included under the various dietary supplement program elements in the CFSAN [Center for Food Safety and Applied Nutrition] 1999 Program Priorities document?
"5. Are there current safety, labeling, or other marketplace issues that FDA should address quickly through enforcement actions to ensure, for example, that consumers have confidence that the products on the market are safe and truthfully and not misleadingly labeled?
"6. Toward what type or area of research on dietary supplements should FDA allocate its research resources?
"7. Given FDA's limited resources, what mechanisms are available, or should be developed, to leverage FDA's resources to meet effectively the objective of the strategy?"
The CFSAN 1999 Program Priorities document is available at http://vm.cfsan.fda.gov/~dms/cfsan199.html. This document "calls for the development of an overall dietary supplement strategy in conjunction with other agency units and stakeholders."
How to Attend or Speak at the Oakland Meeting
This meeting will take place Tuesday, July 20, 1999, 9 a.m. - 5 p.m. at the Oakland Federal Building, Auditorium, 3rd Floor, North Tower, 1301 Clay St., Oakland, California.
"All attendees/speakers MUST pre-register by July 14 by mail, fax, or email to: Janet McDonald, U.S. Food and Drug Administration, 1431 Harbor Bay Parkway, Alameda, CA 94502- 7070, 510-337-6845, fax 510-337-6708, email email@example.com. The following information is needed: name, title, business affiliation, address, telephone number, fax number, and email address. Those wishing to make an oral presentation, either on their own behalf or that of an organization, should so state and provide a brief, written statement of the general nature of the evidence or arguments that they wish to present, name and address of the person giving the presentation, and the length of time requested.
"There will be a five-member FDA panel, including the Director of FDA's Center for Food Safety & Applied Nutrition (Joseph Levitt) and the Director of the Office of Special Nutritionals (Dr. Elizabeth Yetley). A final announcement of the July 20 meeting will appear in the Federal Register around mid-June."
How to Submit Written Comments
"Interested persons may, on or before August 20, 1999, submit written comments to the Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. You may also send comments to the Dockets Management Branch via email to "FDADockets@bangate.fda.gov" or via the FDA Web site, "http://www.fda.gov". You should annotate and organize your comments to identify the specific issues to which they refer. You must submit two copies of comments, identified with the docket number found in brackets in the heading of this document [Docket No. 99N-1174], except that you may submit one copy if you are an individual. You may review received comments in the Dockets Management Branch between 9 a.m. and 4 p.m., Monday through Friday."
How to Obtain Transcripts of the Meetings
A transcript of the Washington meeting, and probably of the Oakland meeting as well, will be placed on the FDA Web site http://www.fda.gov, but not for at least two weeks after the meeting. Transcripts can also be obtained through the Freedom of Information Act, or examined at the Dockets Management Branch at the FDA's office in Rockville, Maryland.
Action Alert: Drug-Patent Bill Could Cost Patients $3 Billion+
Hearing July 1
While this bill does not affect AIDS drugs, activists fear that it could serve as a precedent when AIDS drugs go off patent during the coming years. In addition, the politics around this bill is a grimly fascinating example of Washington at work.
According to the Campaign for Fair Pharmaceutical Competition, "Our biggest problem at this time [is that] Schering is sparing no expense to push the extension through. The company has hired former Senate Majority Leader Howard Baker, Linda Daschle (the current Senate Minority Leader's wife), four other former members of Congress, and more than a dozen other lobby and PR firms to make it happen. Worse, Schering recruited Rep. Jim McDermott (D-WA), a staunch consumer advocate in Congress and a physician, to introduce the bill (surprise, surprise ... Schering is now Rep. McDermott's second largest contributor -- and number one corporate contributor -- even though the company has no operations in his state!) Schering has also recruited 32 other members of Congress as cosponsors of the bill, including Rep. John Conyers (D-MI), a founding member of the Gray Panthers and previously a foe of big brand drug company rip-offs."
Opponents have organized a "Buy Jim Back" campaign, getting people to send $1 each to McDermott to "buy him back" from Schering-Plough, which, according to the Campaign for Fair Pharmaceutical Competition, contributed $7,762.
For more information:
Note: The Campaign for Fair Pharmaceutical Competition is coordinated by National Grassroots & Communication, a Washington D.C. public-relations company which offers "coalition management" and "grassroots organizing," among other services (see "Deforming Consent: The Public Relations Industry's Secret War on Activists," by John Stauber and Sheldon Rampton, http://caq.com/caq/Caq55.prwar.html). The Campaign includes Mylan Laboratories Inc. (a generic pharmaceutical manufacturer), and ten to 15 local senior and consumer organizations in each of several Congressional districts. According to The Star-Ledger (a New Jersey newspaper) of July 21, 1998, Mylan started its own lobbying arm, then called the Coalition for Fair Pharmaceutical Competition, and was at that time its only member ("Generic-Drug Price Hikes Incite Probe," by Edward R. Silverman, staff writer).
[According to National Grassroots & Communication, the Gray Panthers and others were present at the press conference when the Coalition was announced, so Mylan was not the only member. And the "National Grassroots & Communication" described in the Stauber and Rampton article was not them, since the current company only bought the name, not the company, from a previous owner!]
None of which changes the fact that HR 1598 has no purpose except to transfer billions of dollars from patients and the public to some of the world's richest corporations.
Copyright 1999 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.