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Cancer drugs: fact and fiction

Large amounts of anticancer drugs are administered to patients every day in Japan at the discretion of doctors. A few of them have produced dramatic results, but most have not proven effective in prolonging life.

Behind this lies collusion between pharmaceutical companies and medical institutions to grab large chunks of medical spending. For both domestic and foreign drugmakers, cancer patients in Japan have become a “plant on which money grows.”

In general terms, anticancer drugs are quite effective for malignant tumors in hematogenous organs like leukemia and malignant lymphoma. The chance of curing infantile acute lymphoblastic leukemia, once regarded as deadly, has now reached 80 percent while a combination of some anticancer drugs and other treatments has served to prolong the life span of patients with breast, ovary, large intestinal or lung cancer. But these are rare exceptions. Anticancer drugs have not demonstrated clear effects against other types of cancer.

The basic problem lies in the research and development process. In particular, third-phase clinical tests, which constitute the final stage of drug development involving hundreds of patients, are prone to become a hotbed of irregularities as drugmakers’ rise and fall depends on their results.

Specifically, there is a big disparity between patients whose names are registered for clinical tests and those who are actually treated with the drugs. A survey conducted by a group of doctors at the National Cancer Center showed that while relatively young patients are chosen for clinical tests, anticancer drugs are actually administered to older patients, with the median age difference reaching seven years.

The reason is simple. To obtain approval from the Health, Labor and Welfare Ministry, pharmaceutical companies try to make the tests results look as convincing as possible by registering “persons who are sturdy like sportsmen and who have illnesses” for the clinical tests, according to a doctor at the cancer center who took part in a clinical trial of an anticancer drug.

For many years anticancer drugs were routinely administered to patients prior to their death. Even if they develop complications, nobody can determine whether the cause of the complications was a side effect of the drugs or the progress of the illness.

This situation underwent a drastic change in 2001 when Chugai Pharmaceutical Co. and Zenyaku Kogyo Co. started marketing Rituxan to treat malignant lymphoma and Novartis Pharma K.K. launched Glivec to cure chronic myelogenous leukemia. Both are classified as molecular target drugs, which work directly on cancer cells and cause little side effect.

The downside is that they are quite costly. Glivec, for example, costs a patient ¥2,617 for a 100-milligram pill, which must be taken at a rate of four per day, bringing the total annual cost for each patient to about ¥3.8 million.

With some 10,000 patients now relying on Glivec, it has become the biggest source of profit for Novartis, with annual sales of that drug reaching ¥33.1 billion in Japan and $4.746 billion globally.

In December 2013, however, a crisis hit Novartis as the Glivec patent expired, opening the way for its competitors to sell generic versions while Bristol-Myers Squibb introduced a drug called Sprycel having similar efficacy to Glivec.

Alarmed, Novartis developed a successor to Glivec, named Tosigna, and did everything possible to have patients switch to the new drug. Such action became the cause of scandals discovered in clinical tests conducted at the University of Tokyo and Keio University. Although tests were carried out, they should be regarded as Novartis’ sales promotion campaign. Employees of the firm were involved in the writing of the research protocol, the recruitment of patients for the tests and the academic presentation of the test results. The success of Glivec led to introduction of one molecular target drug after another. So far 60 such drugs have been approved in the United States and 37 in Japan.

In the fiscal 2014 list of best-selling drugs, Rituxan ranked sixth with $7.5 billion, Avastin (for large intestinal and other cancers) seventh with $7 billion and Herceptin (for breast cancer) ninth with $6.9 billion — all of them molecular-target drugs.

Except for the success scored by a handful of brands like Glivec, Iressa, Rituxan and Herceptin, other molecular target drugs have proven to be hardly effective. One such example is Chugai Pharmaceutical’s Tarceva, designed to cure pancreatic cancer.

It has reportedly been proven that the new drug prolongs a patient’s life by two more weeks than existing drugs. It sometimes harms the liver or causes interstitial pneumonia. It costs about ¥220,000 per month.

According to a doctor specializing in cancer treatment, the data related to Tarceva were collected by testing more than 500 patients selected by Chugai Pharmaceutical and in relatively good condition. The drug, the expert says, not only is ineffective for patients but also causes side effects.

Even anticancer drugs that are truly effective in treating cancer patients have serious cost problems. The drug called Opdivo (also known as Nivolumab), developed by Ono Pharmaceutical Co. and sold abroad by Bristol-Myers Squibb, works well against malignant melanoma and lung cancer, but it costs a lung cancer patient who weighs 60 kg as much as ¥17.5 million a year. Since a large portion of that cost, above the several tens of thousands of yen a month paid by the patient, is covered by public money under the public health insurance system, it will only leave the insurance scheme’s fiscal health even worse. That has led Seiichi Sato, an expert on treatment using anticancer drugs formerly with the National Cancer Center, lament that “victories by medical science will lead to the nation’s ruin.”

The only way to solve the problem would be to lower Opdivo’s price, but that would be resisted by the pharmaceutical firm because it invested huge sums of money to develop the new drug.

To help sustain the public insurance system, appropriate prices should be set for drugs that correspond to their efficacy. The problem is deciding who will determine the drug prices.

In Europe, the European Medicines Agency has the power to approve the effectiveness of each drug. After approval is given, individual countries take cost effectiveness into consideration and decide whether the drug should be covered by health insurance. In Britain, the National Institute of Clinical Excellence is known for its strict rules. It has rejected insurance coverage for the anti-breast cancer drug Halaven developed by Eisai Co.

In Japan, there is no such strict rule-making body. Not much can be expected of the cost effectiveness panel of the infamous Central Social Insurance Medical Council, an advisory body for the health and welfare minister. The council certified Halaven — the drug that was rejected in Britain — as an innovative product. This represented a political victory for the pharmaceutical lobby.

Cancer patients and their families become desperate in seeking a cure through every means. As if to take advantage of such desperation, all kinds of anticancer drugs, some effective and some not, are prescribed to patients. Patients and their families should find out whether the anticancer drugs that have been prescribed are costly but effective, or whether they just cost a lot and provide nothing more than peace of mind. They should refuse the latter type.

More importantly, people must strictly monitor the pharmaceutical industry with the aim of getting the prices of effective drugs lowered as much as possible. There is a limit to the government’s social welfare spending and its revenue sources are dwindling. Pharmaceutical companies should not be allowed to do as they please with their business model of making easy financial gains with anticancer drugs.

This is an abridged translation of an article from the December issue of Sentaku, a monthly magazine covering political, social and economic scenes.