Extraordinary
Measures
Reforming
China’s Rare Disease Policy
Xiaohe Li, Fei Gao
Published in Chinese 11/21/2010 on Southern
Weekly—“China's most influential
liberal newspaper” (comment by New York Times).
Translated to English by Xiaohe Li
Since rare diseases affect only a small
population, seeking a cure is risky and profitably unappealing to most
pharmaceutical companies. Drugs for such rare diseases are so dubbed “orphan
drugs”. Despite this, rare disease patients in the Western world still benefit
greatly from the support coming from society. The most urgent need for rare
disease care in China is a state law for protection and regulation.
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| The Crowley family. Left: Megan, Aileen, John, John Jr, Patrick. Image: www.crowleyfamily5.com |
The Power of Fatherly Love
When the devastating Pompe disease stroke Megan and
Patrick, rendering the siblings hard to move and even breathe, they were at the
ages of five and four, respectively. Looking at their kids now bound to the
wheelchair and ventilator, Aileen and John Crowley were appalled and in
disbelief. This was because they had
learned, at that time, there was no cure for this disease.
But a father will never give up on his children. As
told in the film based on the real life of the Crowleys, “Extraordinary
Measures,” John became an advocate for Pompe disease, teaching himself both the
science and business of biotech industry, and eventually convincing Genzyme—the
third largest pharmaceutical company at the time—to invest in the orphan drug
development for Pompe. His efforts paid off: a trial drug, later commercially
approved as Myozyme, ameliorated the siblings’ symptoms and saved their lives!
Pompe disease, also known as glycogen storage disease
type II, occurs in less than 1 out of 40,000 people. The disease results from
genetic defects that lead to a lack of glucosidase—the enzyme needed for
breaking down glycogen into glucose. Patients suffer from muscle weakness as
well as cardiac and respiratory complications, with very little chance to live
past 1 to 2 years of age.
According the World Health Organization, a large number of the five
thousand rare diseases are genetic disorders, which means the patients may be continuously
affected by the disease throughout their lives and have the chance to pass on
the defects to their offspring.However, there are fundamental disagreements in the definition of rare disease across countries. The U.S. recognizes diseases affecting less than 200,000—about 1 in every 1,500 people—as rare diseases. However, the qualifying number of patients in Japan is under 50,000, while it is only 2,000 in Australia. The European Union and Taiwan have more stringent standards than the U.S.: affecting 1 in 2,000 or 1 in 10,000 people, respectively. There is no rare disease law in China so far. Yet, according to the definition issued by World Health Organization, China is estimated to have 10 million patients of each type of rare disease—a shockingly large number.
Due to the small and specific market niche,
pharmaceutical companies have been less enthusiastic to invest in the orphan
drug development. Until recently, only a few diseases—including Pompe disease—have
available orphan drugs. Even so, most of these drugs are not a complete cure:
patients usually depend on lifelong treatment to stabilize their disease. On
the other hand, the most promising treatment—gene therapy and stem cell
therapy—are still far away from clinical application.
Contrasting Corporate Cultures
Fortunately, society and the media in China have been
gradually paying more attention to several rare diseases. Notable cases are
thalassemia, brittle bone disease (osteogenesis imperfecta), and phenylketonuria.
A much more heated discussion about another type of
metabolic enzyme deficiency like Pompe disease—Gaucher disease—swept the
Chinese cyberspace. An article about a
U.S. pharmaceutical company maintaining the production line of an old drug for
twenty years only for two Chinese Gaucher disease patients (who are allergic to
the new drug) has been circulated around many popular online forums. The story
has not only won applause for this Good Samaritan company, but also raised
skepticism about its authenticity and even speculation on the unuttered
motivation of the company.
The company in the story is Genzyme, the very same
company that developed the Pompe drug for Megan and Patrick Crowley. From
Genzyme and the National Gaucher Foundation (a U.S. charitable organization dedicated
to this disease) we confirmed the existence of the two allergic patients except
that they are not in China. These two patients are allergic to the newer
version of the life-saving drug (Cerezyme), which is now more easily produced
using cell culture, but not to the older version which is purified from human
placenta (Ceredase). Although it is no more profitable, the production line for
Ceredase has nevertheless been kept running by Genzyme to this day.
This discussion reflected the interesting difference
in the corporate cultures between pharmaceutical companies in China and the
Western world: following a more established tradition of giving back to
society, the Western companies take up their social responsibility, while their
Chinese counterparts somehow failed to realize that the pharmaceutical industry
is more of a moral business. The Chinese society is also less familiar with
this type of corporate moral responsibility, thus more suspicious about any
nonprofit-driven corporate behaviors.
However, Genzyme has indeed been donating drugs to
many Chinese Gaucher disease patients. To verify the story we interviewed Ms.
Xiao Hu, the marketing manager for lysosomal storage diseases at the Genzyme
Shanghai branch. According to Ms. Hu, though Cerezyme was not approved by the
Chinese FDA until 2008, Genzyme already started donating it to Chinese patients
in 1999. This charitable program started with the touching story of a loving
Chinese mother. Desperate to save her son, Ran Ding, a young boy suffering from
Gaucher disease, Ms. Ding wrote to the president of Genzyme for help. Genzyme
then decided to donate Cerezyme, the only available treatment at the time, to
Chinese patients. 134 patients have benefited from drugs worth over $100
million donated by Genzyme in the past 11 years. Ran Ding’s life was saved and
now he is already a college student.
Genzyme has entrusted the Cerezyme donation program to
the China Charity Federation. Based on the agreement between the two
organizations, Genzyme will continue to donate $200 million worth of Cerezyme
in the future.
Patient Support
According to the estimation by Nature Reviews Drug Discovery there are only 5,000–6,000 Gaucher
disease patients in the world. This disease is caused by genetic defects in the
enzyme which breaks down macromolecules. Patients with such conditions will
have macromolecule buildup in cells, and eventually develop bone lesions in
addition to liver and spleen enlargement. Intravenous injection of the enzyme
about twice a week, also known as enzyme replacement therapy, is viewed as the
gold standard of Gaucher disease treatment.
The cost of such treatment varies from patient to
patient, but usually falls between $100,000 and $400,000 annually. This is beyond
the capacity of the average Chinese family. However, due to the lack of rare
disease law, Cerezyme has never been covered by the state health insurance. Most
of Chinese Gaucher disease patients depend on the donation from Genzyme. This
situation has again called for such a law to address the urgent needs of the
patients.
By stark contrast, in the developed world, rare
disease patients are specially protected by the system.
In the U.S., most patients are treated with the
support from various sources—governmental funds (social security, health
insurance subsidies, veteran benefits, etc.), private insurances, and
charities. The reason that expensive
orphan drugs like Cerezyme are covered by insurance is usually twofold: first,
there is no alternative treatment, and second, the small number of patients
will not have a huge impact on the overall cost of health insurance.
In Australia, treatment for Pompe and Gaucher diseases
are among the six orphan drugs that are covered by the special care system. The
Japanese government established a subsidy for patients, with a more favorable
amount for people with lower income. The Brazilian federal government started
to fully cover drugs for Gaucher and Fabry diseases in 2003. In Italy, three
funds were established in 2007 for rare diseases under the Health Ministry. Taiwan
also passed laws to provide full coverage for rare disease drugs and nutrition
supplements.
The Impact of the Orphan Drug Act
Besides legal protection, the more favored status of
orphan drugs has been another factor benefiting rare disease patients.
According to our interview with Mr. Yanjun Zhang, a
researcher in pharmacy administration at the University of Cincinnati College
of Pharmacy, the U.S. Orphan Drug Act of 1983 (the first orphan drug law in the
world) established many favorable policies leaning towards the orphan drug
development. First, pharmaceutical companies of orphan drugs will get tax
credits for 50% of the clinical trial expenses, a waiver for the New Drug
Application fee ($1 million per case in 2008), and research funding from the
government ranging from $250,000 to $300,000 per year. Second, the company who
won the FDA marketing approval of a new orphan drug will enjoy seven years of
exclusivity, during which FDA will not approve another company’s drug for the
same indication. This incentive secures the profit of orphan drugs and thus
greatly stimulates the interest of many companies to invest in orphan drug
discovery.
Following the U.S. many countries have established
similar favoring laws for orphan drugs. In Japan, orphan drugs are favored for
grant funding, tax credits, priority review, and longer re-evaluation periods.
The Australian government also waived the new drug application fee and the
annual registry fee. The European Union extended the marketing exclusivity of
orphan drugs to ten years.
These moves dramatically advanced the orphan drug
development in the U.S. and the rest of the world: between the signing of the
Orphan Drug Act and October 2010, FDA designated 2,233 orphan drug candidates,
among which 352 won the final approval, while in the decade before the Orphan
Drug Act only 10 were approved. What is the most exciting is that these drugs
save thousands of lives.
The small patient population limits the market niche
of most orphan drugs. The complicated etiology of rare diseases further prolongs
the developmental cycle, raises the expense, and complicates the clinical
trials. Even if it did succeed, the profitability of an orphan drug will be
unpredictable. That is what deters small companies away from orphan drug
development and would even give industrial giants like Genzyme cold feet if
there were no protective policies.
Orphan drugs, however, are not free of criticism. The
protective polices have led to the high price of orphan drugs. The lifelong
dependence on the drugs further contributes to the profit of this industry.
Cerezyme, despite its small market, earned Genzyme $1.2 billion in 2008,
capturing the title as one of the most expensive drugs. In fact, the discussion
about the business ethics of orphan drug pricing has led to some legislative
measures to cap the price and the profit.
The Problems Facing China
Based on his evaluation of the Chinese biotech
industry, Dr. Min Wang, Dean of School of Life Sciences at China Pharmaceutical
University, told us that China has no capacity for orphan drug development
because of its “high-expense, high-risk” nature. Nevertheless, for imported
drugs, the Chinese FDA has given priority to orphan drug review since 2009. So,
the best solution is to expedite the registration of foreign orphan drugs in
China in order to save more patients.
Importing more orphan drugs into China is indeed a
needed and practical solution. But the most urgent problem is beyond the medication
itself: China needs a state law to define and defeat rare diseases. As a mother
of a Taiwanese rare disease patient put it, the parents may not be able to take
care of their ill children through their whole lives, but the system should be
and will be.
The care from society is also important. In the
developed world, a complete spectrum of charities has long been established and
exerted their positive influence on the making of rare disease policies. They
are also very helpful in raising support for and defending the rights of
patients.
The good news is that a network of rare disease
charities, physicians, media, volunteers, and patients and their families are
blooming right now in China. The China
Charity Federation has set up voluntary programs for rare diseases and also an
emergency fund last year. Last July, the China-Dolls Center for Rare
Disorders—an organization for the brittle bone disease—aired a rare disease
special on CCTV—China’s predominant state TV broadcaster. All these
progresses—the fruit of the efforts from many groups—have signaled a promising
future of the Chinese rare disease care.
The
authors are college students at Nanjing University and members of College
Natural Sciences magazine.
