Israel Is Almost Alone in Ignoring Rare Disease Research

Imagine you've been appointed head of the panel that decides which new medicines need to be put into the health basket [the 'basket' of health services Israelis can receive from the government] and you're faced with figuring out what to do about a new medicine for heart disease.

Imagine you've been appointed head of the panel that decides which new medicines need to be put into the health basket [the 'basket' of health services Israelis can receive from the government] and you're faced with figuring out what to do about a new medicine for heart disease. It helps only 15 percent of patients, you don't know who it will help until you try it, but it is a successful drug.

This medicine comes on top of about 10 other drugs for heart disease. There is another medicine known to be successful, the only known drug for a serious hereditary illness called Pompe's disease, also known as acid maltase deficiency. But many people suffer from heart disease, and only a few dozen people suffer from Pompe. So which medicine will you choose for the health basket?

This moral issue is not just theoretical. Around 5,000 rare diseases have been classified, a large part of them hereditary, many of them fatal. Since only a small number of people suffer from these diseases, the big pharmaceutical companies tend to avoid investing in research and development for appropriate treatments which have come to be called "orphan drugs."

In 1983 the United States passed a law giving major benefits to drug companies to push them toward developing drugs for these rare "orphan diseases." In 1999 the European Union passed a similar law. And in Israel? Not only is there no legal incentive to develop orphan drugs, but there is not even a mention of such medicines in the law - including any criteria for putting them in the health basket.

American pharmaceutical company Genzyme is one of the most prominent companies in the orphan drug market. In effect, half of the company's income in 2002 - which came to a total of about $1.2 billion - came from one medicine, Cerezyme, which treats Gaucher disease. About 4,000 people worldwide have Gaucher, a genetic disease - particularly prevalent among Ashkenazi Jews - that causes fatty deposits to build up in certain organs and bones. Sufferers need to take Cerezyme every day of their lives, and it costs $170,000 a year.

U.S.-style incentives

Dr. David Meeker, president of Genzyme's therapeutics division, visited Israel last week, among other reasons to learn about Israel's policy on putting orphan drugs in the health basket. In the U.S., he said, there is a consensus that the orphan drug law is one of the most successful on the books. The American law defines an orphan drug as one that treats a disease afflicting fewer than 200,000 Americans, while the European law sets the number at five out of every 10,000 people.

The law grants seven years of exclusive marketing rights to a company that develops an orphan drug in America, and 10 years in Europe, in addition to tax breaks and other benefits, Meeker said.

These benefits are significant. Since the law does not allow some medicines to be patented for various reasons, the decision to provide marketing exclusivity to the first company that develops an orphan drug gives it the security of knowing that it will be able to make a return on its investment in research and development. In addition, American law exempts such companies from having to pay about $300,000 to register the new medication.

Meeker seemed uncomfortable to be reminded that that Cerezyme is one of the most expensive drugs in the world. He said that wasn't exactly so, citing drugs for hemophilia that can cost a million dollars a year. In addition, he said, creating and developing every drug costs a fortune, and the low demand for the drug makes it difficult to lower the price.

Today, said Meeker, Genzyme is at an advanced stage of developing a drug for Pompe. To do the research, he said, the company flew Pompe sufferers from around the world to its research centers, mainly in Britain and Germany, to assure uniform conditions for treatment. First they had to find 16 babies under 6 months old who suffered from the disease; then they had to fly them and their family members to and from the centers every two weeks to get a transfusion. The costs, said Meeker, were enormous.

On average, it takes 10 years to develop a new drug, said Meeker. Once the drug is cleared for use, it's the local health maintenance organizations or health insurance plans that bear the cost of the drugs. Nonetheless, Genzyme has a policy that uninsured sufferers of Gaucher disease get Cerezyme free. About 5 percent to 10 percent of those who have the disease fall into this category, and most of them are from developing countries, said Meeker.

Israel is a rare treasure for Genzyme. Not just does it have a strong and orderly medical infrastructure, but it also has a large population of Gaucher sufferers. That's one of the reasons Israel passed a law in 1994 that made the state responsible for covering the cost of Cerezyme. Worldwide, one in every 100,000 people has Gaucher disease, but in Israel one out of every 1,000 people has it, said Meeker.

Doctors who work in Israeli hospitals say it's hard to find situations in which people stricken with rare diseases do not get treatment, but warn that may change shortly. The health basket committee, say the doctors, does not have criteria that assure separate funding for orphan drugs, which lowers their chances of being funded.

Senior officials in the pharmaceutical industry say the situation has already changed. "In the past, there weren't a lot of orphan drugs, so the HMOs were not required to spend a lot of money on them," said an industry insider. "Today there are more drugs and less money, so the HMOs pressure the health basket committee not to include new orphan drugs, and even to remove orphan drugs that had previously been included."

The industry official brings out official documents written by senior HMO officials in which they admit to acting to remove orphan drugs that had been approved for the health basket. "When there are no rules, it's easy to exert pressure," he said.

The Health Ministry confirmed that no clear criteria have been established for including orphan drugs in the health basket. "Once a year, if there is a budget for increasing the basket, the Health Ministry defines, via the basket committee, which medications are recommended for inclusion in the basket," the ministry spokeswoman said. "Medications intended for rare diseases are judged on the same criteria as other medications, in the framework of the medication basket and medical technologies."

According to Meeker, the Health Ministry's approach is precisely the problem. When orphan drugs are judged for inclusion on the same basis as regular medicines, he said, drugs that treat a greater number of people generally get preference. For instance, cancer drugs are often approved automatically although some of them only help about 10 percent of people with cancer, said Meeker. By contrast, he said, orphan diseases can usually be determined through genetic testing, and doctors can generally tell beforehand whether the drug will work.

In addition, said Meeker, doctors who treat cancer have a large arsenal of drugs from which to choose, while the same laws that provide incentives for pharmaceutical companies to create orphan drugs tend to insure that there is only one drug to treat orphan diseases.

Meeker proposes that decision-makers in the health system looking more closely at how many people are actually helped by a given medication rather than just how many people suffer from the disease the drug treats. If the funding is allocated more judiciously, he said, the health system can save money to fund orphan drugs instead.

However, if the system still does not approve funding for drugs that orphan drugs that can save lives, he added, then additional resources must be allocated to fund orphan drugs.

Drug companies are obligated to develop drugs, said Meeker, and the state is obligated to take care of all its citizens. He added that Eastern Europe, Brazil, Colombia, Greece and Turkey have all decided to adopt the approach that funds must be set aside for orphan drugs. What he wanted to know was, why not Israel?

Zeev Zelig, general manager of Genzyme Israel, thinks he knows exactly what Israel needs to get politicians to understand the importance of orphan drugs. "One sick person," he said. "That's all that's necessary. One sick person who appears on TV, who gets attention, who the decision-makers will speak to. That will be enough."