Ever since we went public with Addi and Cassi’s cyclodextrin treatments, I have received countless emails asking me a number of questions. How did I find the sugar compound "cyclodextrin?" How did I manage to get the Food and Drug Administration to approve infusions of this new compound into Addi and Cassi? As a parent advocate, would I share any knowledge I might have with others facing Rare Diseases?
Before I answer specific questions about the twins’ cyclodextrin treatments, I think it’s important to share 10 Important Lessons I have learned about the drug development process and why I have helped start a Virtual BioTech after Addi and Cassi were diagnosed with Niemann Pick Type C a year and a half ago.
Lesson 1: Understand the drug development landscape: Most pharmaceutical companies will not be of help to you if you are facing a Rare Disease. Here are the stats. Approximately 7000 different Rare Diseases exist. According to the National Institutes of Health, pharmaceutical companies have only developed treatments for 200 of the 7000 Rare Diseases! Thousands of Rare Diseases are not being invested in by pharmaceutical companies because of small patient populations and lack of financial incentives to Pharmaceutical and Biotech companies. This is why the NIH and NCGC have started the Therapeutics for Rare and Neglected Diseases program (TRND). The government has to step in where Pharma and Biotech companies will not.
Lesson 2: What is in the pipeline?: It takes 10+ years to bring a new drug to market and costs 800+ million – if a drug is not already in Phase 2 or 3 for your specific Rare Disease, it’s unlikely that there will be options for you other that what already exists. In most cases, there will be nothing for you or your child since no drug company is going to spend $800+ million dollars on your Rare Disease. How do you find treatments and therapies?
Lesson 3: Create a Virtual BioTech.: Anyone can do this. In the case of Niemann Pick Type C disease, our family has teamed up with three other families (still looking for more to join us!) and we have pooled our resources together to find near term therapies for our children. We named our Virtual BioTech "SOAR-NPC" or Support Of Accelerated Research for Niemann Pick Type C. Last year, the four families raised over $1Million dollars collectively and we are pouring our money into specific NPC research projects.
Lesson 4: Fund collaborative research teams: Currently our Virtual Biotech has 4 key NPC researchers with different skill sets working together and sharing their data. These researchers have agreements with their respective institutions so that they can work together. They work in different parts of the world but talk bi-monthly (before they would meet once a year at a conference) about project plans, deliverables and dividing up the research work. This type of cooperation also reduces duplication of research efforts in laboratories.
Lesson 5: It’s a Business. Hold Weekly Meetings: The SOAR NPC Parents group meets weekly by conference call and at least quarterly in person. We have an agenda that we review that covers topics ranging from fundraising to research. Notes are taken. We divide up tasks that need to be accomplished based on the skill sets of the team.
Lesson 6: Project Managers: We have hired a doctor with a neuroscience background to help us understand the medical literature and he interfaces with our core set of researchers to stay abreast of all current research. This doctor also helped us design and write the FDA protocol on cyclodextrin and is a shared resource for the families. Parents also need to act as Project Managers depending on how much time they can devote to their cause.
Lesson 7: A Focus on Therapies: Off Label Drugs and Supplements: Our researchers are tasked with finding near term treatments for Niemann Pick Type C affected children. We are not focused on finding new drugs to be taken through the pharmaceutical or biotech development process because drugs will not reach our children in time (remember it costs $800+ million to bring a new drug to market). Rather our focus is on the library of already approved 3,000+ FDA drugs that could be used “off label” and re-purposed for our needs. In addition, we are testing over the counter supplements that could be used to help our children today. We have created a master drug and supplement intervention list (“our pipeline”) and have prioritized targets for testing. Next, we test these targets in the Niemann Pick Type C mouse model or in cell based assays.
Lesson 8: Get Involved: It’s not always possible to rely on existing non-profit Foundations to meet your personal objectives. Understand what your Foundations are doing and where they are spending their research dollars. For example, look at the Cystic Fibrosis Foundation which has a terrific model — they publish their drug and supplement pipeline list. Does the Foundation supporting your Rare Disease have a drug development pipeline? If so, ask to see it. Some Foundations may spend their dollars on patient support while others have a focus on basic research that will not produce near term therapies for your Rare Disease.
Lesson 9: Consider treatment options from other diseases that have more research funding: In the case of NPC, there are lots of common symptoms and pathways shared with Alzheimer’s as well as Ataxias. A lot of research has been done in other fields that could be translated to your specific rare disease. For example, Curcumin, a spice from Turmeric, is a good example of a non toxic supplement therapy that has shown to be beneficial in many neurological diseases. But always do your research as there are differences between over the counter supplements. In the case of Curcumin, there is a therapeutic version developed by UCLA Curcumin experts and made by Verdure Sciences and plain over the counter that is not highly bioavaiable in your body.
Lesson 10: Don’t take “No” for an answer: Work with people who believe in the power of “Yes.”
Jay M. Tenenbaum became a multimillionaire in the Internet boom of the late 1990s. But it wasn’t until he was diagnosed with a lethal cancer that he found his calling as an Internet entrepreneur.
Dr. Tenenbaum learned in 1998 that he had melanoma, the most serious kind of skin cancer. He underwent surgery and took an experimental vaccine for a year. Then, nearly five years ago, the cancer returned, having spread to his liver. "That’s when I started looking at my mortality seriously," says the 65-year-old from Portola Valley, Calif.
Frustrated with his treatment options, Dr. Tenenbaum began investigating other potential therapies. He found dozens of patient-advocacy organizations dedicated to melanoma that raised money and supported scientific research. They "all had good ideas," he says, "but no one had put the different pieces together in the right way that would let them make progress in finding a drug in the lifetime of a patient."
So he tapped his own Internet savvy — and his connections — to create a company aimed at helping patients develop new therapies faster and cheaper for less common diseases, like melanoma, that often don’t attract major pharmaceutical company research funding. He set up his new company, called CollabRx, with $2 million he had available and is trying to raise $3 million more from family, friends and private investors.
|Thor Swift for The Wall Street Journal|
|Jay Tenenbaum started CollabRx to help patients hasten drug development.|
Dr. Tenenbaum’s idea taps into the recent phenomenon of patient-supported research — a trend largely driven by people wealthy enough to help fund drug-discovery projects and who are affected by rare or overlooked diseases.
The Myelin Repair Foundation, founded by a patient with multiple sclerosis, set up a team of researchers to come up with promising drug leads. After spending $13 million over four years, the foundation will present its two best prospects to drug companies in coming months in the hopes of getting one of them to develop the drugs further. And the Cystic Fibrosis Foundation, started by a group of parents who had children with the disease, recently announced that a drug it is paying a biotech company to develop showed promising results in an ongoing trial. The foundation says its investment in the drug so far exceeds $75 million.
CollabRx aims to expand patient-funded research further by connecting individuals or small numbers of patients with the tools and services they need. Each CollabRx client is assigned a project manager, a specialist who works with patients to devise a research strategy, interpret the results and later steer any promising prospects toward development of possible treatments.
CollabRx calls such integrated projects virtual biotechs because they aim to replicate many of the steps typically taken as part of a pharmaceutical or biotech company’s search for a new drug. As the number of private labs available to do sophisticated research grows, many parts of the drug-development process can now be contracted separately. Researchers in various locations can share information and material by means of a Web-based network created by CollabRx software engineers.
CollabRx’s fees vary depending on the scope of a project. But Dr. Tenenbaum says he expects to charge most clients a management fee of 10% of a project’s budget and to receive a 20% share of any intellectual property that emerges. Drug screens, clinical trials, and the costs of other contracted services are paid for by the clients.
Dr. Tenenbaum says patients can get started on a project with as little as $50,000 to $100,000. Sums like that, for example, could fund the creation of a molecular profile of a tumor to try to predict what combination of already approved drugs might be effective. If results proved promising, more money could be raised to set up a full-blown virtual biotech — with a budget in the millions of dollars — that might test cocktails of therapies in animal models and try grouping patients into subtypes to better tailor treatments for them, among other projects.
Bonnie J. Addario, a former oil-company executive in San Francisco, is a lung-cancer survivor. When she first started thinking about how to make a difference, she figured, "I’ll run a gala and a golf tournament, raise money for research, and that will be it." Mrs. Addario, 60, raised $800,000 through a foundation she set up in 2006. She distributed the money to a number of researchers, and then realized, "there are a lot of wonderful people doing great work, but lung-cancer survival rates [of 15.5% after five years] haven’t changed for 40 years. Why is that?"
To find answers, Mrs. Addario and her husband, along with David M. Jablons, her surgeon from the University of California, San Francisco, put together a two-day conference last fall of lung-cancer researchers from major institutions around the world. She says the group identified a number of problems that hinder progress toward a cure. Among them: Researchers didn’t know what others were doing, tissue and blood specimens needed for experiments weren’t centrally located or shared, and the findings of experiments weren’t integrated to help assess what the key priorities should be.
Mrs. Addario started a new organization, the Addario Lung Cancer Medical Institute, and hired CollabRx to address some of these issues. The company is helping the institute build a virtual specimen bank where researchers participating in the project can share patient specimens and establish joint standards for collecting future specimens. Using the CollabRx Web-based network, the researchers can share research and ideas, and quickly reprioritize projects as new information comes up. Mrs. Addario says the institute expects to spend at least $5 million over the next year to set up the virtual biotech, fund researchers and establish the specimen bank.
It’s far too early to tell whether CollabRx’s approach will be more successful at finding new drugs cheaper or faster than the traditional methods of drug and biotech companies, a challenge acknowledged by scientists who target faster cures. "We’re not discovering drugs slowly just because of a faulty business model," says John Wilbanks, executive director of Science Commons, a nonprofit in Cambridge, Mass., that seeks to make research more effective by encouraging more open access to scientific data. "We don’t understand so many things about toxicity in the human body. It’s hard because it’s hard," says Mr. Wilbanks, who works with Dr. Tenenbaum on a separate project. On average, the pharmaceutical industry spends about $1 billion over 17 years to bring a new drug to market.
CollabRx’s approach in some respects also goes against the cultural grain of scientific research. In order for academic researchers to get ahead at universities, they must be first to publish breakthrough findings. This competitive culture deters scientists from sharing information, and could make it difficult for CollabRx to get researchers to work together.
The Internet culture that drives CollabRx encourages collaboration, says Christopher P. Austin, director of the Chemical Genomics Center of the National Institutes of Health. "And unlike the Internet, where people were maniacal about sharing stuff, biomedical scientists are exactly the opposite," he says. "You have to drag their data from their cold dead fingers. They do not share." Dr. Austin is testing CollabRx’s network with one of his lab’s projects that seeks to develop therapies for a rare disease.
Dr. Tenenbaum, who has a Ph.D. from Stanford University in electrical engineering and computer science, was deeply involved in the Internet boom of the 1990s. He started a number of Web companies that helped pioneer the use of e-commerce. His most lucrative foray was as chief scientist and a board member of Commerce One Inc., which developed technology enabling the computer systems of big businesses to interact more readily. Dr. Tenenbaum, who goes by the nickname Marty, left Commerce One in 2002 as the company was struggling amid the tech bust early this decade.
Dr. Tenenbaum is engaged in another project with several partners that also borrows from the Internet culture — creating a nonprofit marketplace for data, materials, resources and services needed for studying and treating disease, to be called Health Commons. The partners, which also include Science Commons, the Public Library of Science, and CommerceNet, plan to set up a site where people and companies in the life sciences can go to buy and sell goods and services.
Dr. Tenenbaum says that if Health Commons is successful, it could help CollabRx locate resources for its virtual biotechs. Even individual patients, should they want to pursue research and drug development on their own, could find information and services at the site, he says. (For a summary of the Health Commons project, go to http://sciencecommons.org/projects/healthcommons/.)
Chris and Hugh Hempel of Reno, Nev., last fall met with Dr. Tenenbaum a few weeks after learning that their 4-year-old twin daughters, Addi and Cassi, had been diagnosed with Niemann-Pick Type C, a genetic neurodegenerative disorder that usually is fatal by the age of 20. The Hempels joined with a group of parents to fund SOAR-NPC, a virtual biotech CollabRx set up.
The group decided that the fastest way to help the children would be to focus on a combination therapy of already approved drugs and other compounds that could prevent or significantly delay the onset and progression of NPC. Mrs. Hempel, who runs a public-relations firm, says she and her husband recently raised $500,000 at a gala event in Reno that will help fund the virtual biotech, whose total budget is $1.3 million for the first year. The project currently is testing a number of drug candidates at an NIH-run facility. Later this year, the first human observational study will start.
CollabRx also is helping to coordinate a melanoma study at the John Wayne Cancer Institute in Santa Monica, Calif., which received a grant from the Melanoma Research Alliance. The project, with a budget of $1 million over three years, is using genomic technologies to test melanoma tumors collected by the institute over the past two decades to find drugs that might work on clusters of individuals whose tumors exhibit certain similarities.
The melanoma alliance, set up with funding from Apollo Advisors founding partner Leon D. Black and his wife, Debra, and FasterCures, an organization created by financier Michael Milken, are also discussing a larger project with CollabRx to set up a melanoma virtual biotech. That project would test various melanoma cell lines against existing drugs and drug combinations with the aim of advancing promising prospects to clinical trials. Gregory C. Simon, president of FasterCures, says he sees the melanoma virtual biotech as a model that could be useful to other advocacy groups with which FasterCures works.
It is a project that Dr. Tenenbaum is following closely, not only in his role at CollabRx but also as someone who might benefit from any potential therapies that emerge. Mr. Tenebaum has had four surgeries to remove suspicious nodules since his cancer returned, and he gets scans every few months. Right now, there are no signs of the cancer. "But with melanoma," he says, "that can change overnight."
He plans to contribute funding for the melanoma virtual biotech out of his own pocket. Eventually, Dr. Tenenbaum says he plans to pay to have his own tumor cells tested with whatever drug combinations the virtual biotech finds are promising.
"The fact that there is no therapy right now that works in general for melanoma patients doesn’t mean that there is no therapy that works on selected patients," Dr. Tenenbaum says. "That is where CollabRx comes in. I want to have that information in hand, just in case I ever need it."
Write to Amy Dockser Marcus at firstname.lastname@example.org
No Insurance. No Money. No Drugs. No Hope.
We Need A New RoadMap For The Future
Of 7,000+ diseases that affect humankind, treatments for only 200 of these diseases are being actively pursued by pharmaceutical and biotechnology companies. With the cost of bringing a new drug to market now exceeding $1 billion dollars and taking up to 10+ years to test and develop, global pharmaceutical companies are focused on return on investment.
Meanwhile, millions of people suffering from all types of diseases will never see new drugs reach them or their loved ones in their lifetime. As a nation, we must unite to think about the drug development process in a different way and push for change.
Today, one family is faced with paying $180,000 a year for a highly experimental drug treatment for their two children afflicted with Niemann Pick Type C. Who can afford a single experimental drug at this price? Like millions of others, many Niemann Pick Type C children have no health insurance. No insurance. No money. No drugs. No hope.
The dire situation we are faced with our drug development process is happening across disease states — this is not a unique problem to Niemann Pick Type C. The FDA is in a major crisis and we can no longer continue on this path when millions of lives are at stake. The Addi and Cassi Fund, named in honor of our five year old identical twin girls, plans to bring attention to the drug development crisis and to push for change.
We are building one of the first “Virtual Pharmaceutical” models in the United States with the help of Silicon Valley heathcare company CollabRx. Our Virtual Pharmaceutical is named "SOAR-NPC" (Support Of Accelerated Reserach for Niemann Pick Type C) and we are focused on creating a drug therapy pipeline for NPC afflicted children around the world. If global pharmaceutical companies and the FDA won’t help us save our children by rapidly bringing new drugs to market, we must find solutions ourselves in order to attack and treat a rare and fatal disease like NPC.
One of the greatest resources we have as a nation is our National Chemical Genomics Center. The robotic technology at the NCGC which is pictured above should continue to be invested in by our government — NCGCs technology can find existing drugs sitting on shelves that can be repurposed and used to treat diseases they were not originally intended for. Currently, we are funding the NGCG to test thousands of approved drugs as well as natural supplements against multiple Niemann Pick Type C cell lines in the hopes of finding immediate targets to treat afflicted children.
Every dollar donated to The Addi and Cassi Fund goes directly to cutting edge research projects to rapidly accelerating finding immediate treatments for brain diseases. Translational research – studies that bridge the gap between the discoveries in the laboratory with the need to find ways to intervene in the disease process and treat patients who are living with illnesses – is the roadmap for the future. With your help, we can build this roadmap and prove there are alternative approaches to the current drug development process.
We must seek treatments today and cures tomorrow!