Millions of people in
America suffer from rare, or “orphan,” diseases, conditions defined by the
government as affecting fewer than 200,000 people. With an estimated 30,000
affected individuals, Huntington’s disease is one of the more common of these
disorders.
The pharmaceutical
industry has largely ignored these diseases, which number several thousand,
because each disease promises too few customers/patients to enable companies to
recoup investments in drug research and development and therefore generate a
profit. The market usually doesn’t work for people with these diseases.
News about a lawsuit
by Arkansas cystic fibrosis (CF)
patients against the state’s Medicaid program for its refusal to pay for a
highly effective but extremely expensive drug – Vertex Pharmaceutical’s Kalydeco – shined light on this predicament.
In an article titled
“The $300,000 Drug,” New York Times columnist Joe Nocera recognized Kalydeco as a “wonder drug” but questioned whether the country can
afford the personalized medicine approach that enables scientists to design
specialized treatments for very small and specific groups of patients.
With an annual
wholesale cost of $311,000, Kalydeco was developed for a subgroup of about
1,100 CF patients with specific genetic mutations. The subgroup numbers about
2,150 patients worldwide in an overall CF population of 70,000 individuals.
“Because
patients will likely be taking the drug for the rest of their lives, it could
cost millions of dollars to keep just one patient on Kalydeco,” Nocera
speculated. “That raises another important question about the coming of
personalized medicine. How are we, as a society, going to pay for it?”
Same question for the HD community
The
HD community could face this very same question. Because the U.S. has only
30,000 HD patients and 150,000 to 250,000 people at risk of carrying the gene,
a potential treatment could cost a lot.
Boston-headquartered
Vertex has sought to
develop HD treatments since mid-2008. Though the company has made a substantial
effort, it doesn’t yet have plans for a clinical trial. (Click here to read
more.) Isis Pharmaceuticals, Inc., of
Carlsbad, CA, has also worked about as long and is planning to launch a clinical trial in the next year or two.
It’s
still too early to project the costs of treatments that have yet to be tested
or even fully designed. Other potential remedies are in trials but at best
likely remain years from reaching the market.
Furthermore,
an HD treatment regimen will likely involve a cocktail of remedies, meaning
that patients – via their insurers – will probably have to pay for more than
one drug.
Vertex vice president of research Paul Negulescu (left), Gene Veritas (aka Kenneth P. Serbin), and Vertex vice president of biology Beth Hoffman at the company's San Diego facility, September 2010 (photo by Heather Farr, Vertex)
Patient
assistance programs
The HD community must remain
vigilant regarding the cost of potential treatments. However, failing to
consider a number of factors, the
coverage of the Kalydeco costs was perhaps too pessimistic about the future.
First,
as I commented regarding the impatience with California’s stem cell institute
after ten years of operation without a drug, biomedical research is slow by
nature. And it’s expensive, with the average cost of developing a new drug in
the U.S. at $1.2 billion. Only one in ten clinical trials results in a
marketable drug, although the research from the unsuccessful projects provides
highly valuable information on what does not work.
In
the case of CF, Vertex is at work on another treatment that would reach
thousands more patients with different kinds of mutations.
As
Nocera himself noted, Vertex provides Kalydeco for free to patients without
insurance.
Lundbeck,
the pharmaceutical firm that markets Xenazine, which diminishes some of
the involuntary movements caused by HD (chorea), provides financial assistance to patients who qualify. Depending on the dosage, the annual
wholesale cost of this treatment can reach $50,000 or more, but, according to
the Lundbeck website, “85 percent of U.S. patients taking Xenazine have a monthly
co-pay of $50 or less before requesting co-pay assistance.”
It’s
highly conceivable that the developers of future HD treatments will provide
similar kinds of assistance – especially because these firms will have relied
on the good will and extensive cooperation of HD families who participate in
research studies and clinical trials. However, it’s not clear what the drug
companies will charge insurers.
CHDI and pharma giants
After
the founding in 2003 of the CHDI Foundation, Inc., a non-profit virtual
biotech firm backed by wealthy donors who wish to remain anonymous, pharmaceutical firms small and large started to
gain interest in developing Huntington’s treatments.
As
a result, the network of firms working on HD now includes pharmaceutical giants
such as Pfizer, Roche, and Medtronic.
As
a non-profit with the sole purpose of finding HD treatments, CHDI promotes
research on Huntington’s and the diffusion of scientific knowledge about the disease. With more researchers and firms
involved, the chances for treatments have grown. Having more options could very
well mean that treatments would cost less.
By
pouring hundreds of millions of dollars into HD drug research, CHDI has created
an incentive to produce cheaper drugs.
As
it states on its website, CHDI seeks to connect academic research, drug
discovery, and clinical development in order to avoid “costly delays to
therapeutic development” and make potential treatments a “good investment” that
will result in “full clinical development, including licensure and marketing to
get drugs to HD patients.”
Similarly,
the Hereditary Disease Foundation and the Huntington’s Disease Society of America (HDSA) have supported research that could yield yet
additional drugs.
Patient-driven
medicine
Thanks
to this level of support for HD research, the HD community stands in perhaps a
better position than those facing even more rare diseases.
Nevertheless,
orphan disease communities in general have reason to feel optimistic about both
the development of treatments and their cost, if the vision of one key medical
leader becomes reality.
Lee Hood, M.D., Ph.D., one of the
scientific giants behind the Genome Project and the recipient in 1987 of the
Lasker Basic Medical Research Award (the American equivalent of the Nobel
Prize), has developed a plan for more effective and affordable medicine. In
2000, Dr. Hood
founded the Institute for Systems Biology (ISB). Located in
Seattle, the non-profit ISB teams scientists and technologists from many
disciplines to pioneer the future of research in biology, biotechnology,
medicine, environmental science, and science education.
In
a 2012 speech at the Seventh Annual HD Therapeutics Conference, sponsored by
CHDI, Dr. Hood outlined the importance of systems biology – what I think of as
the “big picture” of disease – for HD research. Dr. Hood also advocated for the
adoption of P4 medicine: predictive, preventive, personalized, and
participatory. (Click here to read more.)
“Patients and consumers will be a major driver in the
realization of P4 medicine through their participation in medically oriented
social networks directed at improving their own healthcare,” Dr. Hood and
Mauricio Flores, J.D., wrote in the March 2012 issue of the journal New Biotechnology.
ISB and several collaborating organizations have run some pilot programs in P4. If it is implemented on a wide scale, Dr. Hood
predicts that it will revolutionize our healthcare system. Everybody will carry
a health-monitoring device, and diseases will be predicted and prevented long
before onset as the result of tiny blood samples taken from a pin prick, the
article states.
Predicting falling medical
costs
Significantly, costs could plummet.
“P4 medicine
will require that all healthcare companies rewrite their business plans in the
next 10 years or so,” Dr. Hood and Flores wrote. “Many will not be able to do
so and will become ‘industrial dinosaurs.’ There will be enormous economic
opportunities for the emergence of new companies tailored to the needs and
opportunities of P4 medicine.”
The
authors projected that savings will result from a series of factors, including
earlier and more effective diagnosis of disease; better matching of drugs with
diseases and their subtypes; better identification of genetically based adverse
reactions to drugs; the ability to “re-engineer” disease-affected biological networks
within people in order to reduce the cost of drug development; an increasing
ability to deal effectively with cancer; the use of stem cells for replacement
therapy and diagnostics; the routine extension of effective mental and physical
health into people’s 80s and 90s; an improved understanding of microbes in the
body; a deeper understanding of neurodegeneration (the cause of HD,
Alzheimer’s, Parkinson’s, and other disorders); and the digitalization of
medical and genetic information.
“On another tact, our
prediction is that there will be a ‘wellness industry’ that will emerge over
the next 10-15 years that will in time far exceed the size of the healthcare
industry,” Dr. Hood and Flores affirmed. “P4 medicine is an area replete with
economic opportunities.”
Dr. Hood and Flores
believe that P4 medicine will “democratize” healthcare.
“The patient
(consumer), through social networks, will drive the emergence of P4 medicine,”
they wrote. “Because of intrinsic conservatism and sclerotic bureaucratic
systems, physicians, healthcare specialists and the healthcare industry will
take a back seat to the power of patient-driven social networks in bringing
change to the healthcare system. Indeed, patients may be the only driving force
capable of truly changing our contemporary healthcare system to the proactive
P4 mode.”
This scenario serves
as a serious alternative to the dim view that orphan disease communities will
remain relegated to high-cost solutions.
Guaranteeing proper care standards
Indeed, a “revolution” has occurred over the past
two decades in how patients have related to their doctors and the
pharmaceutical industry (click here to read more).
Nowadays,
people enter the healthcare system as both patients and advocates for
their well-being.
This
outlook led the Arkansas patients to sue for the right to have their Kalydeco
costs covered.
Their
lawsuit offers a striking similarity with the HD community’s pressure on the
Social Security Administration and Congress to update the decades-old,
inaccurate government criteria for determining disability benefits for
Huntington’s patients (click here to read more). The Arkansas plaintiffs in
effect have demanded that the state recognize Kalydeco as the standard treatment
for their type of CF.
Negotiating the price
The
competition of the marketplace, greater efficiency in drug development, and the
revolution in medicine outlined by Dr. Hood should put downward pressure on the
cost of drugs.
Patient
advocates must play a crucial role in this process.
As
the late San Diego biotech leader Duane Roth had told me during a dinner with California stem cell leaders in 2008, patient
advocates must find ways to appeal to pharmaceutical companies’ primary
interest in profits. Advocates need to lobby and court these business leaders.
At
the same time, disease organizations such as HDSA and its network of advocates can pressure pharmaceutical companies and government
agencies to assure new drugs’ accessibility and affordability.
In
some circumstances, government can join in the process of persuasion and even
play hardball, as the Brazilian Ministry of Health did in the 1990s in order to
convince multinational pharmaceutical firms to dramatically reduce the price of
HIV/AIDS medications. The Brazilian government provides HIV/AIDS drugs for free.
“Local
production of generics, the possibility of breaking patents, and the offer of
technology transfer became instruments for price negotiations with other
countries and the pharmaceutical industry, leading to a real reduction in
prices on the Brazilian and international markets,” wrote the coordinator of
the country’s National STD/AIDS Program.
The
marketplace exists, but it is susceptible to politics.
The
rhetoric about the $300,000 drug can scare a lot of people. But in the long
run, such a cost is not a foregone conclusion.
