When rules about ‘orphan drugs’ go wrong, costs rise

According to a report in the UK newspaper The Guardian, 24 June 2002, the prices of life-saving treatments for some rare children’s diseases are being increased by pharmaceutical companies to levels where UK hospitals can barely afford them.

EU regulations concerning ‘orphan drugs’—drugs which are of benefit to fewer than five per 10 000 people—have been put in place in order to encourage the invention of new medicines. But ...

A chemical manufacturer was reported as being no longer able to provide a hospital with carbamyl glutamate because a pharmaceutical company is in the process of securing a licence and sole marketing rights to the compound under the orphan drug regulation. According to The Guardian, the pharmaceutical company based in Paris, but with a branch in the UK, has increased the price of carbamyl glutamate from around £700–£1500 a year to £80 000–£106 000 (depending on dosage) and will soon have a 10 year monopoly on its supply.

Other examples apparently include sodium phenylbutyrate, which is used to treat a build-up of toxic ammonia in children with the same enzyme disorder, which used to cost £36 for 100 g and now sells for £860 for 266 g, ~10 times the original price. Intravenous ibuprofen, used in premature babies, has risen from <£1.62 per 300 mg ampoule to >£60 for a 10 mg ampoule since the company was given a licence.

A pharmacist employed by the company responsible for the development of carbamyl glutamate is stated to have said that researching the drug and formulating ways to purify the compound had cost money. "For 10 years these physicians have been treating their patients with a chemical and they do not know what they have", he said. The price was justified, in his view, by the quality and safety of the medicine his company was producing.

If this was fiction, no one would believe it

Dr Harold Shipman, the family doctor convicted 2 years ago of murdering 15 of his patients [see Annals of Oncology News 12 (2)], actually killed at least 215 of them, as reported by the world press at the end of June 2002. The killings stretched over a 23-year period in which the friendly and so trustworthy general practitioner systematically injected patients with lethal doses of diamorphine. Dame Janet Smith, the judge in charge of the inquiry, is reported to have said, "The true number of victims is far greater and cannot be counted. I include as victims the thousands of relatives, friends and neighbours who have lost a loved one or a friend before his or her time, in circumstances that will leave their mark forever." Further information can be found on www.the-shipman-inquiry.org.uk.

Some pharmaceutical company officials may need EPO to boost them up, while others celebrate

Johnson & Johnson has had to face tough times in a very rough stock market. Their Puerto Rico factory, which makes Eprex for sale outside the USA, is under FDA inspection and this news has not been well received by analysts, leading to a 16% plunge in the share price. In recent months, health authorities in Europe and Canada have been concerned by a rise in pure red cell aplasia among renal dialysis patients, with 141 cases reported. It is still unclear whether the criminal investigation is related to the health problems in Europe. The Puerto Rico inquiry is possibly connected to allegations by Hector Arce, a former worker at the factory. Mr Arce, who was fired in 1999, contends he was pressed to falsify documents, in some cases to cover up manufacturing lapses. Johnson & Johnson said the factory was inspected by the FDA for 2 weeks in October 2001 and then for 4 days by French authorities in June 2002, both of whom found only minor problems. This was confirmed by Brad Stone, a spokesman for the FDA. "We did do an inspection last year and they came out pretty well", Mr Stone said. "There was nothing we would consider a serious or major violation." He would not confirm or deny, however, the existence of the criminal investigation.

The equivalent of Eprex for the US market is made by Amgen, and is sold as Procrit by Johnson & Johnson and Epogen by Amgen. Cases of pure red cell aplasia have been very rare with these brands. The Roche EPO called Neo-Recormon also seems not to be connected with any rise in the disease.

The incidence of aplasia is said to have started to rise around 1999 after Johnson & Johnson stopped using human serum albumin as a stabiliser, because European authorities were worried about risks of CJD in blood products. The American product still uses the stabiliser. Almost all of the Eprex cases have been kidney dialysis patients who injected the drug under the skin. In the United States, three-quarters of dialysis patients take the drug intravenously. The company has now advised doctors to give Eprex intravenously. This will certainly inconvenience the athletes who misuse the agent to boost their haemoglobin values.

Amgen, meanwhile, can celebrate FDA approval of the use of their long-acting EPO (Aranesp) in cancer patients, only 1 year after approval was granted for its use in dialysis patients.

Hormone replacement therapy: a new scare

Approximately 8 million women in Europe are taking estrogen and progestin hormone replacement therapy (HRT) for various reasons, including relief of menopausal symptoms and possible prevention of heart disease and osteoporosis. They are now asking for guidance as the Women’s Health Initiative study was stopped after an interim analysis disclosed disturbing facts. The study was randomised, placebo-controlled, and estrogen and progestin therapy was evaluated among 16 608 women aged 50–79 years with an intact uterus. Compared with the women who took placebos, the rate of coronary heart disease among women in the test group was 29% higher. The same group had a 41% increase in the rate of strokes, twice the number of blood clots, and a 26% increase in invasive breast cancer rates. The study did find a few benefits from the HRT regimen, including a 37% reduction in the rate of colorectal cancer, one-third fewer hip fractures, and a 24% reduction in total fractures. The rate of cardiovascular disease increased by 22%. At the same time, in JAMA, 17 July 2002, a paper appeared which links HRT to an increased incidence of ovarian cancer. While this latter paper is available for review, the news release at the basis of the present scare has not yet undergone independent analysis.

The women in the Women’s Health Initiative study were given Prempro, a combined equine estrogen–progestin pill that has been the most widely used form of HRT in the USA. Some experts say that this treatment is overdosed and does not represent state-of-the-art. The Women’s Health Initiative is continuing to study the use of estrogen supplements alone in women who have had hysterectomies. This part of the trial was not halted, but will go on as planned until 2005, because there is no evidence that the estrogen alone is causing an increased risk of breast cancer. A subset of the participants in the Women’s Health Initiative study has been undergoing tests of cognitive function to see if HRT affects memory. The results are expected in 2005. There are alternative treatments for symptoms of menopause. Progestin alone prevents hot flashes in ~70% of women, as do some antidepressants. Vaginal dryness can be treated with estrogens that are placed in the vagina but are not easily absorbed by the body. Prevention of osteoporosis can be achieved with raloxifene or bisphosphonates.

World Health Organization, tobacco and taxes

In mid-July 2002, the World Health Organization (WHO) released the draft of a treaty text that will provide the basis for the final stage of the negotiations of a Framework Convention on Tobacco Control (FCTC), a historic step according to WHO officials. The text was put together by the Brazilian Ambassador Luis Felipe de Seixas Correa, Chair of the Intergovernmental Negotiating Body on the FCTC. The new FCTC text, details points of potential agreement on key issues: tobacco advertising, promotion and sponsorship; illicit trade in tobacco products; taxes; international cooperation in areas such as agricultural diversification and financial resources. These points will be considered by the WHO’s member states meeting in Geneva 14–25 October 2002. This is WHO’s first exercise in treaty making and the process is bearing fruit. In addition to the health sector, ministries of finance, trade and foreign affairs, to name a few, have been engaged in the process that diplomats say is a truly multisectorial approach to health. Tobacco is forecast to kill >10 million people per year by the late 2020s if robust steps to curb the epidemic are not taken immediately.

In the meantime, a system that WHO has always suggested would work, and indeed has been proven to do so in many countries, was put to test in the USA. A 40-cent tax rise took effect in Illinois, and the cost of two packs a day went up to US$8.70—US$269.70 per month. Thousands of smokers are reported to have flooded the telephone ‘QUIT’ lines since Illinois raised its tax to 98 cents a pack. Calls to the ‘QUIT’ line, run by the American Lung Association, are financed through the state’s share of the settlement reached with tobacco manufacturers. Illinois is among 16 states that have raised tobacco taxes this year, as budget deficits have collided with an election-year aversion to broader tax increases.





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