HerbalEGram: Volume 8, Number 2, February 2011
A Botanical Look at the Changing Face of Drug Discovery and DevelopmentPlant-focused nonprofit and for-profit companies working to address the global disease burden
Many people say the world revolves around money. There is
perhaps no other place where this rings truer than in the drug discovery and
development industry. Because conventional pharmaceutical drugs are wildly
expensive to bring to market—costing from $800 million to $1.3 billion for a
single new drug product1,2—pharmaceutical
companies must obtain large sums of money from investors. While types of
investors and their aims vary, most wish to a see a maximized return on their investment, which often leads the company to focus on drugs that
will eventually make even more money than was required to fund their costly
journey to consumers’ hands.3
Though this for-profit model has been successful in creating
most new pharmaceutical innovations during the last 3 to 4 decades, gaps in its
ability to address the vast global disease burden are being realized.3,4 Diseases that drastically affect
poor populations, such as dengue fever and tuberculosis, continue to be
neglected by a large part of the pharmaceutical industry, as developing—and
even donating—drugs for these conditions does not usually bring large enough
returns to appease most investors. Likewise, many companies have little
incentive to invest time and money in searching for or developing novel
therapeutics, including (mostly unpatentable) herbal medicines. Fortunately,
however, an increasing number of companies and organizations, including several
focused on plant-based drugs, are taking a different approach.
Nonprofit organizations are being referred to as “more vital
than ever in the advancement of new therapies,” and as playing an “increasingly
important role in drug discovery and development for diseases that are
neglected by the pharmaceutical industry because of low or absent commercial
incentives.”3,4,5 A typical nonprofit
drug company follows a moderate profit-generating model in order to have funds
to reinvest in future projects and to subsidize charitable projects. Instead of
depending heavily on investors, nonprofits seek donated revenue from sources
like philanthropic organizations (such as the Bill and Melinda Gates Foundation,
a major funder of nonprofit health initiatives) and have low overhead costs and
minimal infrastructure. And because they do not have the obligation to produce financial
returns for investors, nonprofits can make their medicines available at a much lower
price, thus reaching underserved populations, focusing on neglected diseases,
and paying attention to novel therapies.
Dozens of nonprofits are currently and successfully working
across the world to discover and create new drugs, including the Institute for
OneWorld Health, the
Myelin Repair Foundation, Medicines360, Battelle, and SRI International,
among others.5,6 Additionally, New Earth BioMed (NEBM),
a newly created nonprofit, focuses solely on discovering multi-compound
botanicals to treat cancer. It receives its funding as donations from individuals, corporations,
and foundations, and through public grants.7
So far supporters include Eric
Potma, PhD, an assistant professor of chemistry at the University of
California-Irvine, who collaborated in developing a “laser bioassay system for
measuring drug effects in three-dimensional co-cultures of cells.” (Individuals
can also donate to NEBM via a simple form on its website.)
NEBM
President, John Boik, PhD, founded the organization in January of 2010. “I
realize that a lot of innovation and beneficial products have been produced by profit-maximizing
corporations,” said Dr. Boik, “but at the same time I see that profit
maximization is not always in line with maximizing the benefit to humanity. I
simply wanted to keep some distance from the for-profit world, as I thought
that in the long run it would allow me greater freedom. Of course, that also
means that our organization is at the mercy of funders” (e-mail, January 27,
2011).
But
because NEBM focuses on the pre-clinical drug discovery phase of bringing a
drug to market, obtaining adequate funding is, theoretically, somewhat less of
a hurdle than if it focused on the following and most expensive phase of drug
development, mostly due to expensive clinical trials. “So while we do
not need several hundred million dollars to do our work, we still will need 10
million or so to get all our work done. Our plan is to start with one study and
move on from there, building funding relationships as [we] demonstrate more and
more success.”
Still, this experience has not been easy, as NEMB needs to
obtain the remaining funding for its first research project, which is projected
to cost about $300,000 and of not all of which has been covered yet. Making
this particularly challenging is NEMB’s unique situation. Not only is it a nonprofit drug company, it is also a
nonprofit drug company that focuses on botanicals.
“It is quite difficult to convince foundations and other donors that ours is a
worthy cause. It is especially difficult in these hard economic times, as
foundations are beseeched with requests. In addition, we have the handicaps
that we are a new organization, without a track record, and that we are
studying something very unusual. We don't just study natural products against
cancer; that is unusual enough. We study large mixtures of natural products,
containing say, several dozen compounds.”
But this aspect of NEBM that might surprise potential donors
is what fuels the optimism in Dr. Boik, who is an acupuncturist and Chinese
herbalist and has a doctorate degree in cancer research. He has also authored 2
books, Natural Compounds in Cancer
Therapy (2001) and Cancer and Natural Medicine (1996) (both of Oregon Medical Press). While
creating his own Traditional Chinese Medicine practice in Portland, Oregon, he
wanted to focus on a specific condition in order to set his services apart from
the milieu of others in the city. “I thought about it overnight,” he said, “and
by the morning had chosen cancer. That defining decision changed my life, and
from that moment on cancer ruled me. I believe the work [NEBM is] doing is very
worthwhile. We are pushing the envelope and I am optimistic we will find the
support we will need, or the support will find us.”
Specifically, Dr. Boik believes that large, nontoxic, and
synergistic mixtures of natural products from the plant world have vast
potential to treat cancer. “Think of these mixtures as a magic shotgun shell
against cancer,” he said. “From a biological perspective, it makes more sense
than a magic bullet, which is the kind of drug that most pharmaceutical firms
focus on. The more key processes you can affect in a cancer cell, the better
your chances of thwarting its proliferation. Not only can a large mixture
affect many biologic processes, each individual compound can be used at a low
and nontoxic dose. Thus both efficacy and safety could be increased.”
NEMB’s long-term goal is to conduct a screening program of
natural product mixtures against cancer cells. Meanwhile, it is at work on its short-term
goal of developing a 3-dimensional bioassay co-culture that more closely
resembles the nature of tumor growth in humans as opposed to the 2-dimensional,
flat, and single-cell bioassay systems typically used in cancer drug discovery.
“If we are successful,” said Dr. Boik, “it will bring us a huge step closer to
being able to develop a mixture screening program that produces results that
are highly relevant to what might occur in humans. [In addition], there could
be some intellectual property developed that has value, and in time it could
help us pay for continued research work.”
While nonprofits are serving a very important role in drug
discovery and development, sometimes their success and level of impact are
dependent upon collaboration with for-profit drug companies, quite a few of
which are doing their part to address the global disease burden. Johnson &
Johnson, for example, granted development and access rights of its experimental
tuberculosis drug, TMC207,
to the nonprofit Global Alliance for TB Drug Development in 2009,8
and Glaxo Smith Kline, in partnership with the Malaria Vaccine Initiative, worked to develop a malaria
vaccine for African children. 3
Likewise, Napo
Pharmaceuticals—whose lead drug candidate, crofelemer, is an isolated and purified
extract from the bark latex of the Amazonian Croton lechleri tree—aims to
focus on international public health issues and ensure that crofelemer is
accessible to all people who need the medicine, especially pediatric
populations. According to Steven King, PhD, Napo’s vice president of sustainable supply and ethnobotanical
research, the company is able to do this through partnering with
nonprofits, such as the International
Centre for Diarrheal Disease Research in Bangladesh and Direct Relief
International, the latter of which distributed the dietary supplement version
of crofelemer to clinics in 30 countries that treat HIV/AIDS patients (e-mail,
January 24, 2011).
“In many ways,” said Dr. King, “we are working to change the
paradigm of for-profit drug development companies by focusing on global
populations simultaneously via our international partnerships so that people
most in need will also have access to this anti-diarrheal drug. It has been and
continues to be part of our core values to implement this strategy and vision.”
Additional charitable activities include Napo’s partnering
with the Healing Forest Conservancy (HFC), which was developed by Shaman Pharmaceuticals, Napo’s
precursor.9 HFC returns benefits to and shares
profits with the indigenous cultures that work at harvesting or replanting
medicinal plants used by the company or who have traditional knowledge. Additionally,
Napo’s B Corporation subsidiary Crofelemer Access Program Global provides
“economic alternatives to tropical deforestation in rainforest areas of
different biodiversity-rich Andean nations.”
In addition to partnering with nonprofits, Napo also creates
innovative partnerships with other for-profit companies and has a number of
investors who are interested in putting money toward the company’s triple
bottom line approach. This approach, explains Dr. King, includes traditional
investors; Napo’s partners in Latin America who have traditional knowledge on Croton lechleri, sustainably harvest the
latex from the tree, and also work to create sustainable alternatives to
deforestation; and persons who are dying of diarrheal diseases from unclean
water, cholera, and other infectious origins.
Even as a for-profit drug company, Napo’s (and Shaman’s)
journey has not always been smooth. Near the end of 1998, Shaman had almost run
out of money and in 1999, results from a clinical trial focusing on crofelemer
for chronic diarrhea (as opposed to acute) showed that patients taking crofelemer did not improve
significantly more than those taking a placebo.10 The company’s stock fell, Nasdaq
removed it from its listing, and many of Shaman’s employees were let go. But in
2000, founder Lisa Conte refined her focus on proving that crofelemer could
treat HIV- and AIDS-related diarrhea with an extended application to irritable
bowel syndrome (IBS). Conte brought Shaman into bankruptcy, founded Napo, and
began new clinical trials. Crofelemer has since received fast-track status from
the US Food and Drug Administration for its IBS and HIV indications.9,10
“There are several important drugs for international public
health programs either on the market now or in process,” said Dr. King. “We
feel crofelemer will be a very important tool [for] global public heath and
also an important product for the Western developed market or ‘biodiversity
poor nations’ as well.”
—Lindsay Stafford
References
1. Pharmaceutical
Research Companies Receive Approval for 34 Innovative Treatments in 2009. New
Drug Approvals in 2009: Presented by America’s Pharmaceutical Research
Companies. The Pharmaceutical Research and Manufacturers of America. Available
at: www.phrma.org/new_drug_approvals.
Accessed October 1, 2010.
2. Woodcock J,
Woosley R. The FDA critical path initiative and its influence on new drug
development. Annu Rev Med. 2008;59:1-12.
3. Hale VG, Woo K,
Lipton HL. Oxymoron no more: the potential of nonprofit drug companies to
deliver on the promise of medicines for the developing world. Health Affairs. 2005;24(4):1057-1063.
4. Matter A,
Keller TH. Impact of non-profit organizations on drug discovery: opportunities,
gaps, solutions. Drug Discovery Today. 2009;13(7-8).
5. Moos WH, Mirsalis
JC. Nonprofit organizations and pharmaceutical research and development. Drug Development Research 70:461–471
(2009).
6. Scudellari M.
The profits of nonprofit: the surprising results when drug development and
altruism collide. The Scientist. 2011;25(1):54.
9. Lindner KS.
Blood of the dragon: the sustainable harvest and replanting of the Croton lechleri tree. HerbalGram. 2009;84:56-65. American
Botanical Council.
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