Lamivudine

Concerns about intellectual property rights were raised this week after two multinationals said they would allow local companies to copy their patented drugs. Nico Vermaak, a director at patent attorneys D M Kisch, says the landmark decision means that the value of patents could be eroded. The first licence, from GSK, has been offered to Thembalami Pharmaceuticals, a joint venture between Adcock Ingram and Ranbaxy. GSK will consider applications for another two possible licences. The deal allows drugs to be exported by local manufacturers to all 47 sub-Saharan countries and copies of these drugs to be imported into South Africa. Anyone owning patents will be wary in South Africa, says Robert Appelbaum of Moss Morris Attorneys, which represents Boehringer Ingelheim, the owner of the Nevirapine patent. However, opponents of patent protection say patents create monopolies, restrict competition and deny mostly poor people access to life-saving drugs. Aids treatment lobby Treatment Action Campaign (TAC) welcomed the moves by GSK and Boehringer Ingelheim. The TAC's view is that the current system of patent protection does not promote research into diseases that affect third-world countries and that big business focuses on drugs that will be bought by rich, developed nations. There is a need for new, creative ways of spurring research and development, says lawyer Jonathan Berger. (Source: Adele Shevel, Sunday Times, 14/12/2003)

There is an urgent need for local suppliers of anti-retrovirals (ARVs), according to people living with HIV/Aids, pharmacies and manufacturer GlaxoSmithKline. This was highlighted by shortages this week in the supply of ARVs to South Africa. Despite the government's decision to roll out the provision of ARVs, a lack of planning has meant temporary shortages - and could presage future crises if problems are not dealt with. This week, GlaxoSmithKline lost two batches of 300mg Retrovir (AZT) in transit. The pharmaceutical company's spokesperson, Vicki Ehrich, described the loss as a rare short-term hitch, but concurred that an alternative local supplier would be helpful. GlaxoSmithKline, she said, had done its bit by granting a voluntary licence to generic drug manufacturer Aspen Pharmacare for the manufacture and sale of three anti-retrovirals - Epivir (3TC), Retrovir and Combivir - in 2001. Aspen Pharmacare is, however, still awaiting approval from the Medicines Control Council (MCC) to manufacture the drugs. A pharmacist who did not want to be named said her pharmacy was having trouble estimating the demand for the ARVs every month. Aspen's Philip, also citing the ever-increasing infection rate in South Africa, underlined the need to nurture a domestic pharmaceutical industry. It does help to have the medicines available locally. Such a factory would also be at the MCC's doorstep to inspect and monitor quality control. But Treatment Action Campaign spokesperson Mark Heywood attributed the current shortage to the incompetence of pharmacies and suppliers: You can always plan for emergencies. He said local drug manufacturers could be part of a back-up plan should imported supplies fall short. (Source: Jaspreet Kindra, Mail and Guardian, Johannesburg ,12 December 2003 )

JSE Securities Exchange listed pharmaceutical company Aspen Pharmacare (APN) has entered into an agreement with the US-based Clinton Foundation for the manufacture of antiretroviral (ARV) medicines. Former US President Bill Clinton announced in New York that his Foundation has reached an agreement with Aspen and selected other leading multinational generic drug manufacturers on a major reduction in the price of HIV/Aids medicine. As a result, it will be easier to make life-saving drugs widely available to people with HIV/Aids in the developing world, Aspen said in a statement on Friday. ARVs supplied by these companies have been certified to be of high quality by the World Health Organisation and the Medicines Control Council of South Africa (MCC). This agreement will allow the delivery of life-saving medicines to people who desperately need them, Clinton said. It represents a big breakthrough in our efforts to begin treatment programmes in places where, until now, there has been virtually no medicine, and therefore no hope. Stephen Saad, Aspen Group Chief Executive said: As Africa's largest generics manufacture, this agreement further endorses the Group's quality manufacturing, scientific and development capabilities, placing Aspen in a league with the leading international generic pharmaceutical manufacturers. Aspen has continually stated its commitment to contributing toward the fight against the HIV/Aids pandemic, and this was recently evidenced by the launch of Aspen Stavudine - the first generic ARV developed and manufactured in Africa, Saad said. This initial ARV demonstrates Aspen's commitment to healthcare in southern African and underlines the scientific and manufacturing capabilities that exist within the country at Aspen's Port Elizabeth based research and production facilities. He added that Aspen is presently in the process of enhancing its manufacturing facilities with the addition of a new multi-million rand oral solid dosage manufacturing facility to service both domestic and offshore markets. The agreement covers ARVs delivered to people in Africa and the Caribbean where the Clinton Foundation is working with governments and organisations to set up country-wide integrated care, treatment and prevention programs. Under the Clinton Foundation agreement, the price of one of the commonly used triple drug therapy combinations will be available for less than US$140 per person per yea - or 36-38 cents per person per day - a reduction of one- third to one-half in the current price of drugs in the developing world, said Clinton. Saad said Aspen's ARV offering should be bolstered shortly by the addition of Didanosine, Lamivudine, Zidovudine, the Lamivudine/Zidovudine combination and Nevirapine which have been submitted to the MCC for registration. These additional licenses were made available to Aspen through arrangements with Bristol-Myers Squibb, GlaxoSmithKline and Boehringer Ingelheim. As a result of the voluntary licenses secured, Aspen infringes no patent regulations. The Clinton Foundation has been working with the companies on this agreement over the course of the past nine months, focusing on ways to reduce their costs and scale up production of the so-called triple drug cocktails, which can substantially extend the lives of people living with Aids and help prevent mother-to-child transmission of HIV. ( Source: , Business Day 24 October 2003)

The Competition Commission's recommendation last week that drug firms GlaxoSmithKline and Boehringer Ingelheim be forced to allow cheap generic copies of their AIDS drugs to reach the South African market goes to the heart of the pricing war being waged by AIDS activists. The Treatment Action Campaign and the other activist groups that initially brought the complaint to the commission last year argue that, despite recent cuts, the prices charged by the pharmaceutical firms for their life-prolonging AIDS medicines are still excessively high. These drugs are not like aspirin, you can't substitute one with another, says Jonathon Berger, a researcher with the AIDS Law Project which represents the complainants. The commission said Boe hringer and Glaxo had contravened the Competition Act by abusing their dominant spots in their respective antiretroviral markets, engaging in restrictive practices such as denying competitors access to patents. Of course we have dominant market position (with nevirapine), we invented it, says Boe hringer spokesman Kevin McKenna. He says the commission's finding is absolutely false, misleading and mischievous, as Boe hringer's South African arm has gone to great lengths to reduce the local price of nevirapine. It sells nevirapine to the private sector in SA at R360 (excluding VAT) for a month's supply, down from just more than R1100 in 2001. McKenna says the parent company is sympathetic to further price reductions. We cannot possibly match generic prices, but we've slashed the price of Viramune to the pain threshold. It's wrong to say we are preventing access, he says. He emphasises that the firm has granted Aspen Pharmacare a voluntary licence to manufacture generic nevirapine. The drug is still awaiting registration by the Medicines Control Council, and once registered may only be sold to the public sector which does not yet provide antiretrovirals to AIDS patients. McKenna says the licence stipulates public sector sale since that is where there is greatest demand for the low price drugs. Berger disagrees, saying patients in both the public and private sectors need a sustainable supply of affordable AIDS drugs. Glaxo, which dominates the AIDS drugs market, holds patents on AZT (branded Retrovir), lamivudine (3TC), and the two combined (Combivir). However, as the commission was issuing a media statement on its ruling last Thursday, Glaxo said it had slashed its public sector prices of its drugs in developing countries, and extended the licence it had given to Aspen for manufacturing generics to include the private sector, and other sub-Saharan countries. As with generic nevirapine, Aspen still awaits registration of its generic versions of Glaxo's drugs. Glaxo and Boe hringer say the commission's announcement took them by surprise. Boe hringer says an earlier complaint of excessive pricing brought against them by the local arm of Indian firm Cipla was dismissed. Glaxo has quietly been negotiating with complainants. Neither Berger nor Glaxo's lawyer Anthony Norton will say what has been discussed. It is likely pressure is being brought to bear on Glaxo to issue more voluntary licences for its medicines and thus drive price competition in the generics market. It is still possible for the complainants to withdraw their case, but it will not necessarily help the drug firms since the commission would not be bound by such a settlement, and could still refer the matter to the Competition Tribunal for prosecution. (Source: Tamar Kahn Business Day 21 October 2003) //\//Links The press release by GSK: http://www.gsk.com/index.htm Glaxo spins local slap into global pat on the back Business Report, 17 October 2003 http://www.businessreport.co.za/index.php?fArticleId=262769 Aids drug makers face stiff penalties Business Report, 17 October 2003 http://www.businessreport.co.za/index.php?fSectionId=&fArticleId=262808 The press release by the competition commission (abridged): The Competition Commission has found that pharmaceutical firms GlaxoSmithKline South Africa (Pty) Ltd (GSK) and Boehringer Ingelheim (BI) have contravened the Competition Act of 1998. The firms have been found to have abused their dominant positions in their respective anti-retroviral (ARV) markets. In particular the Commission has found the firms have engaged in the following restrictive practices: 1. Denied a competitor access to an essential facility 2. Excessive pricing 3. Engaged in an exclusionary act The Commission has decided to refer the matter to the Competition Tribunal for determination. The Commissioner at the Competition Commission said these practices violate the Competition Act of 1998's prohibitions against excessive pricing (section 8(a)), refusing access to essential facilities (section 8(b)) and exclusionary acts that have an anticompetitive effect that outweighs technological, efficiency or other pro-competitive gains (section 8(c). The original complaint in this matter was filed by Hazel Tau and others alleging that GSK and BI were charging excessive prices to the detriment of consumers for their patented ARV medicines. Comment by Jonathan Berger, AIDS Law Project,Centre for Applied Legal Studies University of the Witwatersrand, can be seen on the Druginfo e-mail discussion list archives of 20 October http://lists.healthlink.org.za/cgi-bin/lyris.pl?visit=druginfo

The reduction will drop the price of Combivir, an HIV/Aids treatment recommended by the World Health Organisation, to 90 cents a day in 63 developing countries, including South Africa. The pharmaceutical company announced it would also reduce the price of Epivir, commonly known at 3TC and Retrovir, also known as AZT, by 45% and 38% respectively. TAC spokesperson Nathan Geffen said the price reduction was not being made available to pharmacies which was where most patients obtained their medication. Only about a 1 000 people get their medication through the public health system. Most people get their medication in the private sector. Geffen said the only way of keeping prices substantially low was through generic competition. He said GlaxoSmithKline also needed to clarify if it was going to lower the price of Lamibudine. Combivir is made up of AZT and Lamibudine. He said while Glaxo's action was insufficient, the positive side was that the drugs were being offered to employers who were treating their workers who were not part of medical aid plans. Jean-Pierre Garnier, Glaxo's chief executive, emphasised yesterday that this was not its first price cut. Glaxo has said it has trebled sales from two million people treated to six million in the 63 poorest countries between 2001 and 2002. Sales had not increased much since the last price cut, but manufacturing processes had improved. (Source: Sapa, Guardian Newspapers Limited 2003, Sapa,29 April 2003)

US-Based AIDS Healthcare Foundation is planning to file a complaint with the SA Competition Commission against pharmaceutical giant GlaxoSmithKline, in a bid to widen access to AIDS drugs. The attorney representing the foundation in SA, Musa Ntsibande of law firm Strauss Daly, said yesterday that the complaint would argue that Glaxo abused its dominant market position in contravention of the Competition Act, and was engaging in excessive pricing of its drugs to the detriment of the consumer. Glaxo holds the patent for the antiretroviral medicines AZT, Lamivudine (3TC), and a combination of the two (Combivir), which are used to treat HIV-positive patients. Glaxo is opposing a lawsuit brought against it by the foundation in the US, in which the foundation is challenging Glaxo's patent on the drug AZT The foundation's US attorney, Ron Katz, said yesterday that the foundation was challenging Glaxo on the grounds that it had defrauded the US patent office. The foundation was therefore seeking to have the patent declared invalid, he said. The foundation describes itself on its website as the largest specialised provider of HIV medical care in the US. Its presence in SA is confined to a pilot HIV/AIDS treatment project in KwaZulu-Natal, which it established last year in partnership with a local nongovernmental organisation called Netcom SA, to provide antiretroviral medicines. The pilot programme's doctor, Paul Musoke, said that more patients could be treated if the drugs were cheaper.(Source: Tamar Kahn: Business Day, 28 January 2003)

The European Union is taking measures to prevent low cost drugs intended for patients in some of the world's poorest countries from being diverted and resold for huge profits in the West. By clamping down on the illegal trade in reimported drugs that undercuts standard European prices, the EU is hoping to encourage pharmaceutical companies to expand the trend of making medicines available at special rates to the developing world. The initiative comes amid growing evidence that cut price drugs are being diverted onto the European market. Recent investigations by Belgian customs authorities uncovered large quantities of GlaxoSmithKline productsnotably Combivir (zidovudine) Epivir (lamivudine), and Trizivir (abacavir)destined for Africa being sold in the European Union. Under the scheme, which covers both patented and generic products, companies will register with the European Commission the drugs they intend to sell at lower, tiered prices. These would then be stamped with a highly visible special logoa light blue capital E surrounded by 15 gold stars to alert customs that they should be banned from re-entering the union. To qualify for the register, the commission has, for the first time, proposed a definition of low cost, tiered pricing. The drugs must be sold at either the cost of production plus 10% or at a price reflecting 80% off the average ex factory price in member states in the Organisation for Economic Cooperation and Development. Initially, the scheme will only cover medicines for the prevention, the diagnosis, and the treatment of HIV/AIDS, tuberculosis, and malaria and will apply to 49 least developed and 23 other low income countries, mainly in Africa and Asia. Announcing the plan, Pascal Lamy, the EU trade commissioner, said: The EU wants to set an example with a practical means of helping poorer countries struggling with public health crises. Vaccines and contraceptives have long been available at affordable prices now developed countries need to make an effort with other medicines. He added that the initiative was a concrete example of the trade liberalisation commitment made during last year's negotiations in Doha, Qatar, and was just one element of a broader poverty reduction and health programme for the developing world. The commission is confident that the governments in EU states will approve the plan before the end of the year, and it is hoping that other major pharmaceutical producing countries, notably the United States, will follow its example. However, it also acknowledges that to a large extent the success of the scheme will depend on the vigilance of customs authorities. Source: BMJ 2002;325:1058,9 November 2002 .

WASHINGTON Nearly $18 million worth of reduced-price HIV drugs intended for impoverished Africans have been intercepted by profiteers and shipped back to Europe to be sold at marked-up prices, according to a current investigation. As a result of the scheme, nearly a quarter of the supply of the anti-retroviral drug Combivir that was intended for African patients has not reached them in the last year, said the drug's manufacturer, GlaxoSmithKline. Instead, it and two other Glaxo HIV drugs were sold in Germany, the Netherlands, Britain and Switzerland by European wholesalers that now are under investigation. Glaxo used air-freight companies to transport the medicine to Africa. On the ground, according to the documents and Glaxo executives, the shipments were moved from one company that handles customs clearances on imports to another, and then to an air-freight service employed by the profiteers and flown to Europe. Delivered to wholesalers there, the drugs made their way into the regular chain of commerce. Because the drugs were identical to European versions, the pharmacists who bought them could innocently have thought they were their usual orders, Salet said. After agitation by AIDS activists to improve access to treatment in developing countries, Glaxo discounted Combivir, which costs between $4 and $6 a pill in Western Europe, to 80 cents a pill in sub-Saharan Africa. The diverted medicines were intended for use in Congo Republic, Senegal, Ivory Coast, Togo and Guinea-Bissau, according to European sources. The scheme involving Glaxo's products has been going on since at least July 2001 but was undetected by the drugmaker and European regulators until this July, when customs inspectors in Belgium noticed irregularities in a shipment sent from Senegal. Glaxo estimates that 28 shipments of Combivir, Epivir and Trizivir were diverted, totaling close to 3 million doses. Those shipments, worth $18 million retail, moved from the five African countries through Paris and Brussels, then into Antwerp, the Belgian city where inspectors noticed discrepancies in July. None of Glaxo's discount customers complained that they had not received their products, a lapse that might be explained by inventory problems or delays between shipping and billing. The Washington Post Friday, October 4, 2002

Hopes for a new treatment for hepatitis B have been boosted with the announcement yesterday of a R9,3m Innovation Fund research grant to researchers at the University of the Witwatersrand. Between 5% and 10% of South Africans are chronically infected with the virus, which is transmitted through blood. Most carriers do not exhibit symptoms, but about 25% of them develop potentially fatal liver cancer as a direct result of the virus. The Wits research team, led by Patrick Arbuthnot, is developing a hepatitis B therapy, which inhibits the ability of the virus to replicate in the human body. There are two licensed drug therapies available for treating hepatitis B,but they are not always effective. Interferon alpha works by boosting the patient's immune system to fight off the virus. Lamivudine blocks the machinery inside the virus that is responsible for making genetic material (DNA), and thus inhibits replication of the virus inside the body. The new therapy being developed by Arbuthnot and his team is based on ribozyme technology. Therapeutic ribozymes also inhibit viral replication, but in this case by cutting the molecules in the genetic material of the virus. He said the technology developed at Wits had been protected by a provisional patent. When it was refined the team would seek an international patent. The efficacy of the ribozyme gene therapy application developed at Wits in preventing the hepatitis B virus from replicating has been proven in cell cultures. However, Arbuthnot said work had still to be done to improve its efficacy, and determine its safety in humans. He said it would be at least two years before clinical trials were likely to begin. The World Health Organisations said about 380-million people worldwide suffer from chronic hepatitis B. Although there were slight variations in the strains of the virus found in Africa and Asia, Arbuthnot said the technology he and his team were developing would be effective worldwide. Arbuthnot praised government's preventive efforts, saying that SA was one of only a handful of African countries to immunise children against hepatitis B. (Source: Business Day, 16 July 2002)

In a move that could reduce the price of AIDS drugs for poor countries, the World Health Organisation (WHO) released its first list of safe HIV-related medicines on Wednesday. The list released this week includes 11 antiretroviral drugs and five drugs for opportunistic infections. Of the total, 26 came from major manufacturers and 10 were from leading Indian generic drug producer, Cipla. The company was one of the first generic manufacturers to offer cheaper AIDS drugs to African governments. The decision means that there will be price competition among manufacturers of important antiretroviral treatments. Cipla products include nevirapine, zidovudine (AZT), and lamivudine (3TC), which make up a common AIDS cocktail. International humanitarian organisation, Medecines sans frontieres (MSF), welcomed the involvement of generic manufacturers but expressed concerns about the process used. MSF regrets that the WHO prequalification process was started too late and that it has been so slow, considering that the first expressions of interest from producers were received in December 2000, the organisation said in a statement. WHO was still reviewing other products and suppliers and would add them to the list once they had met the set standards, they added. The absence of essential drugs such as fluconazole - used for treating thrush and cryptococal meningitis - was also a concern, as this would give users a false impression about their quality, the MSF statement added. To access the list: http://www.who.int/medicines/organization/qsm/activities/pilotproc/suppl... (Source: IRIN - Plus News, 22 March 2002)