Pharmaceutical Firms Pledge HIV/AIDS R&D for Resource-Poor

Last week, after meeting with pharmaceutical executives from 17 different firms, UN Secretary-General Ban Ki-moon announced that major pharmaceutical firms were pledging to invest more in research and development on HIV/AIDS treatments and diagnostic procedures for poorer and resource-limited regions, as well as prevention and vaccines.

Despite research developments and new products, inequities in access to medicines continue: "We noted that despite the gains, the epidemic continues to outstrip our best efforts. Only one-third of those who need antiretroviral treatment in low-and middle-income countries are getting it." The Millenium Development Goal 6 is specifically concerned with achieving universal access to HIV/AIDS medicine by 2010 and the halt of the spread of the disease by 2015.


The firms that met with the UN Secretary-General included Abbott Laboraties, which has been in the press for its controversial pricing of Norvir following the marketing of its newer drug, Kaletra.



Access to information is also an important factor in achieving these goals, and China is recognising the significance of data-sharing in disease control. An international team of researchers investigating HIV infections in southern China has been granted full access to government medical data, as reported in Nature. This transparency is advocated as part of China's overall strategy to reach its goal of limiting total infections to 1.5million by 2010.

SA Medicines Bill Approved Amid Widespread Condemnation

The controversial South African Medicines and Related Substances Amendment Bill 2008 was approved by the Parliamentary Portfolio Committee on Health this week.


Although the Bill still has to go before the full Parliament in September, it is expected to be passed into law.


The amendment establishes a new State regulatory authority, the South African Health Products Regulatory Authority, replacing the Medicines Control Council (MCC). The MCC is currently the national competent authority for the approval of new medicines to be marketed in South Africa.


The controversial aspects of the new law are its granting of ultimate decision-making authority to the Minister, its changes to the appeals process and ultimate authority on marketing decisions.


Under the new section 15 "Certification and registration of products", the Minister can choose to refuse approval of a new drug for marketing, after it has passed clinical trials and has been cleared by the Regulatory Authority. The Minister can refuse to register a product if it is considered contrary to the "public interest" - in this decision the Minister is to take account of:

1. public health interests;
2. economic interests in relation to health policies;
3. strategic interests in relation to health policies;
4. the need and desirability for such produch; and
5. generally whether the public would be best served by such registration.

The amendment to section 24 and new section 24A establishes a new appeals process which allows opposition on any grounds (not just scientific) to the decision of the Regulatory Authority or the Director-General. But it appears that the amendments do not provide for appeal against the decision of the Minister.

The Bill has been strenuously opposed by pharmaceutical companies and patient groups alike. It is described as replacing the role of the regulatory authority with an appeals process and a Ministerial decision. Critics have suggested that this leaves the process vulnerable to abuse, mis-use by competitors and interference from policy positions.

In particular, South Africa's track record on the approval of anti-retrovirals is very worrying if this system goes ahead. At the XVI International AIDS Conference 2006, the UN Special Envoy criticised South Africa's approach to prevention and treatment, and others called for the resignation of the Health Minister, Dr Manto Tshabalala-Msimang. The Health Minister had insisted that the South African display include garlic, lemons and African potatoes (pictured at right). Soon after the international meeting and with ongoing public pressure, South Africa appeared to respond with a change in policy but with the removal last year of more progressive Deputy Health Minister, Nozizwe Madlala-Routledge. AIDS activists called the sacking "a dreadful error of judgment." Earlier this month the Health Minister declined to attend this year's XVII International AIDS Conference in Mexico City.

Dubbed as Dr Beetroot, Dr Garlic and worse, there is a dedicated "SackManto" website and in 2007 scientists wrote a joint letter of protest to President Mbeki. But he has continued to give the Health Minister's position his full support.

Treatment Action Campaign (TAC) former chairman, Zackie Achmat, has stated that the new structure will compromise the independence of the Regulatory Authority and "will leave it vulnerable to political interference." TAC has opposed the Bill and has declared it will take action to prevent the Bill becoming law. Many groups are said to be prepared to take legal action if the Bill is passed into law in September in what is described as one of the most important pieces of health legislation in South Africa in recent years.

Thailand - Compulsory Licensing Will Continue

The Public Health Minister, Chavarat Charnvirakul (pictured right), has declared that compulsory licensing of essential medicines will continue in Thailand, despite ongoing pressure from international pharmaceutical companies.

The announcement comes after months of speculation as to whether the health policy would continue, with the election of a new government in April this year. And it follows reports of lobbying of the government by Sanofi-Aventis to purchase its product.

Wichai Chokewiwat, Government Pharmaceutical Organisation (GPO) chairman, is reported as stating that Sanofi had offered to compensate the GPO by selling its products at a discount in Thailand.

Meanwhile, The Nation has reported today that a group of 500 HIV/AIDS activists and patients have challenged Sanofi-Aventis to take its claims to the Central Administrative Court. The challenge is to put in a public forum claims made in a confidential letter to the Commerce Minister requesting a review of the enforcement of compulsory licensing of docetaxel (for which a licence was issued in January this year).

The president of the Thai NGO Coalition on AIDS, Supattra Nakapiew, is reported as stating "We want Sanofi Aventis to file a lawsuit with the Central Administrative Court because we want this case to be a test for the enforcement of compulsory licensing of life-saving drugs in the future."

Before the end of this month, a joint committee meeting of senior officials from the Public Health Ministry, Commerce Ministry and Foreign Ministry together with other interested parties (including civil society organisations and the Pharmaceutical Research and Manufacturers of America, PhRMA) will decide on solutions to access to essential medicines in Thailand and the best means by which these can be delivered.

Rising Drug Prices - The Real Devil in the Detail

Decisions not to supply certain drugs on national health schemes may be an inevitable consequence of a wider problem of rising prices for a growing number of patented medicines. The recent NICE preliminary decision to advise the UK National Health Service (NHS) against several high-priced treatments for advanced renal cell carcinoma was largely attributed to the high cost of these medicines.

In an article last week in USA Today it is suggested that a small number of prescription brand-name medicines in the US, still protected by patents, are being raised in price by 100-1000%. Overall, price rises last year were around 7.4% on average for brand-name drugs in the US.

While patents potentially preserve prices against oversight by conventional competition, pressure is coming from elsewhere. In December 2003, Abbott Laboratories Inc raised the price of the HIV/AIDS drug, Norvir (ritonavir), by just over 400% (from USD205.74 to USD 1028.71 for 120 capsules). In May of 2004, the US-based civil society coalition, Prescription Access Litigation (PAL) filed a class action lawsuit in Illinois state court against Abbott and in October 2004 filed a federal class action suit in the US District Court in California.

Only last week did Abbott agree to settle the lawsuit (the decision awaits approval and the final amount will depend upon the decisions of the 9th US Circuit Court of Appeals regarding the antitrust questions in the case).

But Abbott faces potentially larger damages in the lawsuit filed in October 2007 by pharmacies and wholesalers, and joined by competitor GSK. The case goes before the US District Court Judge Claudia Wilken next week.

The problem is a kind of pharmaceutical BlackBerry issue. Norvir, which received FDA approval in 1996, is a Protease Inhibitor (PI) and is an essential component in highly active anti-retroviral treatment (HAART) used to treat HIV/AIDS. Although initially marketed as a standalone PI, Norvir subsequently became more commonly used in low doses as a booster in HAART.

Abbott then introduced Kaletra around 4 years later as a fixed-dosed combination product and the only such product to include Norvir/ritonavir. The wholesale price of Norvir was then raised in 2003, but not that of Kaletra (despite containing ritonavir). Raising the price of Norvir effectively raised the price required to access the 8 out of 9 competitors' drugs that rely upon Norvir as the booster in HAART. Kaletra thus became a cheaper alternative, but not necessarily a medically-appropriate one for all candidates. The Kaletra patent does not expire until 2016.

According to reports in the San Jose Mercury News, San Franciso, internal memos at the time warned that if the price of Norvir was raised, Abbott would come off as the "big, bad, greedy pharmaceutical company."

As much as I wouldn't want to give up my BlackBerry, it seems the Norvir stranglehold puts quite a bit more at stake.

Innovations in Access - Priority, Pools and Policy

Priority Review Voucher

Amendments to the US Food, Drug and Cosmetic Act Administration (FDA) come into effect next month, with the issue of the first priority review vouchers expected. The amendments, introducing these vouchers, were proposed to provide new incentives for research into neglected tropical diseases. The bill was introduced by Senators Sam Brownback (Republican, Kansas) and Sherrod Brown (Democrat, Ohio) in 2007 and signed by President Bush in September that year.


The Food and Drug Administration Amendments Act (HR 3580) amended Subchapter A of Chapter V of the Food, Drug and Cosmetic Act (21 USC 351, et seq) inserting Section 524 and introducing a system of priority review vouchers for companies seeking to register drugs and vaccines for neglected tropical diseases.

The effect of the voucher is to gain fast-track approval for other drugs that company may seek to register in the future, potentially reducing registration times by almost a year. Following Section 524(b)(3)(B), the first voucher may be expected 27 September, ie, one year on from the date of enactment (Presidential assent).

Regulatory delays are frequently cited by pharmaceutical companies as costly inefficiencies, thereby making a system to mitigate these delays very financially attractive to the industry. However, concerns have been raised. Although the vouchers ideally become important and valuable commodities to facilitate partnerships and to sell onto other companies and thus finance clinical trials for partnerships researching in these neglected diseases (amendments in June provided for the transferability of the vouchers), some have cautioned that the system will not necessarily drive new research. Rather, in some cases they will simply entice companies to seek US registration of drugs already on the market in other countries, with the benefit to the company of a very bankable voucher without the social benefit of new research. Others even doubt the value of the voucher, suggesting that the era of the blockbuster drug is over.

The research qualifying for vouchers might also be limited, with vouchers being available only for registration of drugs containing active ingredients not previously approved. This has been noted as a potentially serious limitation of the scheme, with no incentive for research into new uses for existing formulations and new combination therapies.






Patent Pools

Another significant initiative in access also in the press is that of patent pools. Following the briefing on the UNITAID Patent Pool at the 17th International AIDS Conference, currently underway in Mexico City, James Love explains the major features of the UNITAID patent pool:

• the pool is created as a voluntary mechanism;


• patent owners have the opportunity to identify the field of use for patents licensed to the pool;


• patent owners may exclude countries to which the licence will not apply.

Patent pools are not new, one of the first dating back to the 19th century when a group of sewing machine competitors (including Singer) decided in 1856 to cross-licence rather than decimate their profits by suing each other. This kind of business model persists today and is arguably of very significant application when it comes to medicines.

The Universities Allied for Essential Medicines (UAEM) this week endorsed the scheme: "UNITAID steps forward as a visionary leader in the global fight against diseases affecting the poor." UAEM has called upon universities to endorse the scheme and to contribute to the scheme through consultation with present licensees and through reservations on future licences.

Generics remain instrumental in facilitating access to treatment in developing countries, and at a time when generics are credited as dominating the US Global AIDS initiative, concerns have been raised regarding the scope of the proposed Anti-Counterfeiting Trade Agreement (ACTA). In comments on the proposed agreement, the Generic Pharmaceutical Association (GPhA) urged the US Trade Representative (USTR) "not to allow the rising momentum behind a global anti-counterfeiting strategy to be diffused by deviating into expanded IP protection and enforcement with respect to patents and data exclusivity." Today, a sign-on letter was released by Essential Action and others, urging negotiators to publish the draft text together with pre-draft papers and criticising the ongoing secrecy of the negotiations.

Comments Invited on UK Policy in Access to Medicines

Meanwhile, research is currently taking place into UK Government policies on access to medicines, with consultation with industry, government departments and other stakeholders due to take place in the first half of September. The draft report, being prepared by Emma Back and Samia Saad, will be published in early October on which there will be further consultation later that month. The report will ultimately inform the subsequent edition of the UK's Good Practice Framework, to be managed by the Department for International Development (DFID) in conjunction with Business Enterprise and Regulatory Reform (BERR), Department of Health (DH) and the Intellectual Property Office (IPO).

Comments on key issues to consider and address are invited by the consultants. These should be provided in no more than two pages and no later than 22 August 2008. These may be sent directly to Emma Back (emma.back1@hotmail.com) and Samia Saad (samiasaad@gmail.com).

Traditional Healers Trained in HIV Health Care

The fight against HIV/AIDS in Haiti is being strengthened by a collaboration between medical practitioners and traditional voodoo healers.

Recognising the important relationship between people living in rural Haiti and traditional healers, training in identifying symptoms and advising on treatment is now being provided to traditional healers.

Since most people would consult a traditional voodoo healers for advice, Promoteurs Objectif Zéro Sida (POZ) in Haiti have launched projects to bridge the cultural and technical divide between traditional medical knowledge and western medicine. POZ also provides referral cards to the 30 healers trained in treatment and prevention advice, who sent 360 patients to the conventional HIV testing centre and clinic. (At left: Aurore Julien Brazier, community nurse at POZ's main health clinic in Montrouis)

In recognition of its work, POZ was recently awarded the UNAIDS/UNDP Red Ribbon Award, which is being presented at the International AIDS Conference in Mexico City this week.

POZ is also a partner of Alliance which works towards community action to fight AIDS in developing countries.

Nigerian Law to Increase Local Production of Essential Medicines

Nigeria is about to pass a law to allow local manufacturers to produce drugs to treat malaria and HIV/AIDS, two of Nigeria's most deadly diseases, according to a recent Reuters report.

According to the report, current production levels of necessary drug treatments are insufficient. At present, 14 companies in Nigeria are producing anti-retroviral (ARVs) for the treatment of HIV/AIDS and 8 are producing artemisinin-based combination therapies (ACTs) for the treatment of malaria. At the current levels of production, local companies are able to meet only 30% of the demand for malaria drugs, the rest being supplied by imports from China. Artemisinin (chemical formula at right) is extracted from Artemesia annua, mostly grown in China, but Chinese experts are advising programmes to grow the plant in Nigeria to meet higher production levels.

Ahmed Abdulkadir, special adviser to the Nigerian president, heads a taskforce to produce the essential medicines. In an interview with Reuters, during an anti-malaria conference in China, Abdulkadir said, "We will try to have the legislation passed. We've done all administrative work, it's at the final stage." He said further, "We will dismantle all those barriers so that our local industries are able to produce all of these drugs," explaining that local drug companies were preparing for increased production levels following the passage of the new law. As well as lessening the need for imports, Abdulkadir explains that the law would allow Nigeria to supply west and central Africa.

The World Health Organization (WHO) reports that between 300 and 500 million people contract malaria every year (map at right), with over a million fatalities (1 person every 30 seconds). The vast majority of these deaths (90%) occur in Africa, and most of the victims are children.

The WHO also reports that there were 4.3 million new infections of HIV/AIDS in 2006, with 2.8 million (68%) occurring in sub-Saharan Africa. In 2006, 2.9 million people died from AIDS related illnesses. In Nigeria, largely due to the HIV/AIDS epidemic, there has been a decrease in average life expectancy since 1991, to just 45/46 years (m/f).

Aldulkadir says that the WHO (of which Nigeria became a member in 1960) insists developing countries are given access to these essential medicines, "and that is what we are trying to make sure we have."