'Parents' needed for 'orphan' diseases
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Judy Siegel-Itzkovich, THE JERUSALEM POST Aug. 7, 2005
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People are flattered when they're described as "one in a million," but it's not
an honor if the reason for the distinction is that they suffer from a rare
"orphan disease." There are an estimated 6,000 such disorders, many of them
inherited and half of them diagnosed in children. When taken together, they
affect more than 10 million Americans and about 60,000 Israelis.
Although people generally have sympathy for parentless orphans, governmental
authorities and the pharmaceutical industry generally don't have much compassion
for patients with disorders so rare that developing an effective treatment or
cure would bring minimum financial return.
But speakers at a recent Jerusalem conference on orphan diseases noted that
treatments not only help patients become fully functioning individuals rather
than people needing constant medical care, but also allow family members to
function normally. An additional boon is that research into the mechanisms
behind rare diseases, particularly those due to defective genes, often leads to
greater understanding of other diseases. AIDS, by the way, was at one time
considered an orphan disease.
But the 150 people who attended the symposium held at the Mishkenot Sha'ananim
Adenauer conference center, organized by the Israel Medical Association (IMA)
and sponsored by Genzyme-Israel (subsidiary of the US company that specializes
in developing orphan drugs), heard that Israel is doing much less for orphan
diseases than most other Western countries.
In the US, a law was passed in 1983 to encourage drug companies to finance
development of treatments for rare diseases. The FDA has a special Office of
Orphan Products Development (OOPD) headed by Dr. Marlene Haffner and with 21
staff members to ensure that the law is implemented. The European Community,
Japan, Singapore and Australia are among countries with orphan disease laws, but
Israel still has none. It does, however, have a volunteer organization called
EITAN (the Israel Association for Rare Diseases, headed by computer specialist
Leon Musikant), which serves as an umbrella organization and lobby group.
A private members' bill has been initiated by former health minister MK Nissim
Dahan and MK Dr. Leah Nass to set up a special fund for orphan diseases, and the
IMA has proposed that a law provide tax incentives and other benefits to local
orphan drug companies. Unfortunately, the Health Ministry has not yet held
discussions on whether it will back such initiatives.
This is ironic, since some orphan diseases are "Jewish diseases," resulting from
inbreeding in Ashkenazi or sometimes Sephardi communities. These include
Gaucher's disease (which is already treatable) and still-incurable ones such as
Tay-Sachs, familial dysautonomia, Canavan's disease and Neiman-Pick. Since very
soon more Jews will be living in Israel than any other country, it's obvious
that work on rare Jewish diseases should become a focus here. In addition, there
are rare diseases that affect the Arab community. And there are also orphan
disorders, such as Fabry disease, which are not specifically Jewish disorders
but for which effective treatment has been found.
Haffner, a physician with the title of rear admiral in the US Public Health
Service and recently named an honorary fellow of the UK's Royal College of
Physicians, was a featured speaker at the Jerusalem symposium.
A Jew who began her career as director of health services for the Navajo Indian
population in the US, she has headed the OOPD since 1987. Her office administers
$13.5 million each year in grants for clinical trials involving orphan products.
To facilitate the development of safe and effective treatments, and to resolve
issues related to patient access, she works closely with the pharmaceutical
industry, academic institutions, individual researchers, medical professional
organizations and patient advocacy groups.
Haffner has also been very active in helping groups outside the US develop
orphan drug programs, so her willingness to come to Israel and speak at the IMA
symposium was regarded as significant. When presented with the Royal Society
honor, she was told: "What you have done as director of OOPD has touched the
lives of people in the UK more than Congress ever imagined when it enacted
orphan drug legislation... And your accomplishments over the years have had a
massive impact in Britain as well as the US. It's our way of saying 'thank
you.'"
She told the Jerusalem symposium that orphan drug legislation and institutions
should be adapted to the medical and cultural needs of each country. The
definition of a "rare disease" is flexible, she says, as in the US it includes
disorders suffered by up to 200,000 people (or one in 1,300 Americans), but the
European Union sets the limit at one in 2,000, Japan at one in 2,500 and
Australia at one in 15,000. She said there are diseases known to exist in only
one living person (who inherited rare defective genes from both parents).
Companies such as Genzyme, Emgen and Genentech that produce medications for
orphan diseases are entitled by law to seven years of exclusive sales in the US,
tax credits for clinical development costs, a waiver for user fees (which can be
substantial) and grant support. Haffner stressed that there are "no expensive
drugs, but expensive diseases" and that while medications that save the lives of
orphan disease patients or make their lives worth living usually cost a lot, the
financial benefit of allowing them to work and be productive often makes the
drugs cost effective.
Since 1983, 269 orphan drugs have been approved for use in the US. "Every
additional orphan drug that is approved prevents an average of 211 deaths in the
US each year," she said, "thus some 100,000 have not died due to these
treatments."
The cost of developing orphan drugs, Haffner added, has dropped, while the
number of potential patients has increased, as they somehow appear in doctor's
offices when word gets out that treatment is available.
THE SECOND guest speaker from abroad was Prof. Robert Desnick, head of the Human
Genetics Department at New York's Mount Sinai Medical Center, who has had a key
role in the development of orphan drugs, including Cerezyme for Gaucher's
disease and Replagal for Fabry.
Considered "the father of orphan diseases" with expertise in oncology, gene and
cell medicine, pediatrics, obstetrics and gynecology, Desnick is a regular
visitor to Israel. Besides diagnosing and treating patients (many of them with
Jewish diseases), Desnick has published over 530 research papers and edited nine
books.
He also heads a large lab at Mount Sinai that conducts research in human
genetics and uses molecular biology, protein chemistry, enzymology and cell
biology techniques. He is proud to have been the initiator of Dor Yesharim, a
Jewish organization launched in New York to determine whether young religious
Jews are carriers of severe inherited diseases before they get engaged.
Desnick was among the first to demonstrate the effectiveness of enzyme
replacement, bone marrow transplantation and special drugs for the treatment of
genetic diseases. He is especially involved in storage disorders, in which one
or more deficient genes result in the absence of a vital enzyme. This causes the
accumulation of harmful substances in the body. In Fabry disease, for example, a
shortage of of galactosidase A causes victims, mostly males who inherited a
defective X chromosome, to store a type of fat.
Usually first noticed in children, if untreated it culminates in cardiac,
cerebrovascular and end-stage renal disease, but treatment with the synthetic
enzyme constitutes a cure, Desnick told The Jerusalem Post in an exclusive
interview.
After he showed that replacing defective enzymes could prevent the devastating
consequences of a group of conditions known as lysosomal storage diseases, he
dedicated his career to taking this concept from the lab to the bedside. He and
colleagues, who cloned the defective gene that causes Fabry, have been seeing
patients with that disease since 1966, and have accumulated 2,000 names.
Enzyme replacement therapy for Fabry (which can be diagnosed prenatally) is
included in Israel?s basket of health services for the estimated 30 local
patients who have it. The annual cost per patient is NIS 500,000. Although
initially only two Fabry patient's were diagnosed here, more have appeared in
recent years, causing the health funds to lobby, so far unsuccessfully, for it
to be removed from the basket.
The Mount Sinai physician believes that evolving knowledge of genetics will
eventually spin off a whole host of new therapies including protein replacement,
gene therapy and stem cell treatment. High rates of intermarriage among American
and other Diaspora Jews, Desnick concluded, will lead not only to the
disappearance of many self-identifying Jews, but also to fewer Jewish orphan
diseases.
"Jews led the way with research on Gaucher's disease. Because of their genetics,
Jews have been leaders in the detection and prevention of inherited diseases,
and premarital and prenatal screening has been amazingly successful in
preventing the birth of infants with Tay-Sachs and other horrible illnesses. It
is important to treat these diseases, but even more vital to prevent them."
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