Lead Author: Bruce Bloom
Organization: Cures Within Reach
500 million people worldwide suffer from one of 7000 unsolved diseases. The current pharma system “solves” 10-30 diseases each year and creates costly solutions. That isn’t enough! We need to produce more treatments for patients. We know how!
Thousands of cheap, widely available generic drugs can be “repurposed” to create treatments for unsolved diseases. Repurposing means taking a drug approved for human use in one disease and clinically testing it to determine if it provides a benefit for patients with a different, unsolved disease. Generic drug repurposing is a powerful solution for common diseases like TB, and for rare diseases. Our small NGO has already repurposed generic drugs, saving lives and hundreds of millions of healthcare dollars annually. We have a new idea that can help us scale these successes.
A Social Impact Bond (SIB) “pay for success” model could financially support generic drug repurposing, using healthcare savings generated when a repurposed therapy improves patient outcomes to repay “investors” who fund the repurposing research.
Pharma supports research that creates a drug selling for a price high enough to recoup the research investment and make a profit. Most generic drug repurposing won’t make a profit, so pharma won’t undertake generic drug repurposing. Foundations, NGOs and government support generic drug repurposing research, but funds are scarce and insufficient to cover the $8-$40M to support research and regulatory approval often required to support more physicians to prescribe the repurposed drug to patients.
A SIB “pay for success” model can fill this gap. We are currently developing a Generic Drug Repurposing SIB in England, and the UN could help us speed development and expand it globally. A Generic Drug Repurposing SIB is a simple, safe, cheap and rapid solution to a complex problem, and it will work in every country and for many diseases.
Our solution is called the Generic Drug Repurposing Social Impact Bond (SIB). It creates an unique and powerful economic engine that drives the development of “new” repurposed treatments and cures for some of the 7000 unsolved diseases in the world that impact over 500M people around the world. We do this by clinically testing whether a generic drug already approved for human use in one disease can create a treatment or a cure for a different, unsolved disease.
We know it is possible for a drug approved for one disease to help a different disease - up to 20% of the drugs physicians prescribe for their patients are prescribed for a disease for which they were not originally developed and for which they are not currently approved. This is called “off-label use” and it works very well in many cases.
We could create treatments for many unsolved diseases by just repurposing generic drugs and nutriceuticals already widely available for human use and very affordable, with a high success rate and low investment costs to supplement the great work done under the current pharmaceutical model of creating a new drugs.
There is no capital market economic incentive for testing the repurposing potential of the 3000+ widely available and inexpensive generic drugs that have been approved for human use, or the 2500+ additional safe non-drug supplements (nutriceuticals) that have drug-like biologic impact in the body. A Social Impact Bond sets up a non-capital market economic engine, allowing investors to take the risk that they will get paid back when the drug repurposing research creates two simultaneous successes-improving patient outcomes and reducing healthcare expenses. Only when both happen does the payer have an obligation to pay, but when both happen the patient impact can be life changing and the healthcare savings can be substantial.
1) Impact on remedying policy incoherence
Modern day governments in most countries provide healthcare for citizens with disease, or mandate its provision by others. The costs of providing healthcare are burdening governments as they strive to help the billion people around the world with a chronic or acute disease. Government goals are to improve health and decrease costs, but the government policies and resources often create decreased healthcare outcomes and increase healthcare costs, creating huge policy incoherence.
Governments and other payers look to the pharmaceutical and medical device industries to provide solutions for most diseases. De novo development has created many life-saving therapeutics, and needs to be continued. However, de novo development usually takes as long as two decades or more to get from concept to patient impact. This is way too long for patients, many of whom die before a solution is discovered. These industries create, on average, 10-30 new drugs and devices to solve some of the 7000 unsolved diseases, leaving many diseases available to be tackled by generic drug repurposing.
These de novo solutions are almost always very expensive. Research cost estimates range from $1.4B-4.6B per approved de novo drug, which covers the actual drug development cost, as well as the costs of all of the failed drug development during the same time frame. Governments want more solutions at a lower cost, but seem to have regulations and incentives that favor expensive and slow de novo drug development. And governments don’t have good supplements to this standard drug development system.
The reason that more generic drug repurposing solutions haven’t been delivered to patients is that there is often no natural economic incentive for the repurposing of inexpensive and widely available generic drugs. Generic means that the drug is off patent, so there is no intellectual property protection to allow one company to be “corner the market” and charge a price high enough to recoup its investment, so no company will make the investment. The pharmaceutical model of investing in a new, patent protected drug that can be sold for 7-10 times the original investment works well for drugs with intellectual property protection, but it does not work for the repurposing of generic drugs. A different economic system is needed to drug repurposing, so patients can get the benefit of both de novo drug development therapies and generic drug repurposing therapies.
The Generic Drug Repurposing SIB creates a new economic engine for the repurposing of generic drugs by tapping into a different source of funding, healthcare savings, through the use of a “pay for success” strategy. When a repurposed generic drug is proven, through a clinical trial, to work in an unsolved disease, it improves healthcare outcomes for patients with a disease. When the drug works, the patients often no longer need the palliative medicine and hospitalization they needed when they didn’t have a treatment that worked.
This improvement in patient outcomes can significantly reduce the healthcare expenditures for governments and other payers, who no longer have to pay for other expensive treatments for these patients, including hospitalization, surgery, drugs and devices. It also reduces many expensive indirect costs, such as loss time at work for patients or for caregivers, social services, disability payments, workplace adaptions, and government supported caregiving and housing.
A portion of those savings can be used to repay the impact investors who fund the generic drug repurposing research. Any additional pay for success funds would be used to fund additional generic drug repurposing clinical trials in other unsolved diseases, creating a virtuous economic engine that can bring inexpensive and safe repurposed treatments to patients in need, especially patients with rare diseases, neglected diseases, acute diseases and diseases of the poor, all categories that are a challenge for the pharmaceutical model, and all diseases that cause patients a lot of suffering and payers a lot of cost.
The news gets even better. When a repurposing solution works for patients in one country, it is likely to work for and be available to patients in every country where the generic drug is available. So clinical trials only need to take place in one country for patients in all countries to benefit. That reduces the costs of the clinical trials. And when a repurposed drug solves one disease, it can often quickly be repurposed again in a different but similar unsolved disease, creating even greater leverage.
The Generic Drug Repurposing Social Impact Bond works best when more payers participate. The more each payer participates, the smaller percentage of the healthcare cost savings each payer needs to contribute from their healthcare savings in order to repay the impact investors and create a pool of funds for the next group of repurposing clinical trials. A global Generic Drug Repurposing Social Impact Bond would be a powerful solution to the unmet needs of 500M people around the world suffering from an unsolved disease.
The United Nations has the reach and influence to create such a vehicle for healing and economic benefit. The UN has already done great work on innovative funding options for health, including the IFFIm vaccine bond program and UNITAID, both of which have delivered therapies to specific patient populations that would not have received these therapies were it not for these UN programs. It is unlikely that the UNITAID airline tax fund for improving HIV outcomes would have been possible without the global influence and coordination of the UN. And it is also unlikely that the IFFIm vaccine bond program could have received the multiple countries financial backing that makes it such a powerful investment, without the UN coordination and support.
That same UN power to create collaboration and support is necessary for the full impact of a global Generic Drug Repurposing SIB.
2) Impact on public health
Historically at Cures Within Reach, and based on statistical analysis of the success of Phase II and III de novo drug discovery, we estimate that 10-30% of the generic drug repurposing clinical trials can create a "new" treatment that meets both the patient impact and cost savings requirements. And the clinical trials are relatively inexpensive and quick to get started in most cases, so the patient impact can happen and the evaluation of success can be assessed in a short period of time.
The team at Cures Within Reach has been focused on generic drug and nutriceutical repurposing since 2010, and through 50 proof of concept clinical trials we have created 13 repurposed treatments that are either being used clinically off-label or moving to commercialization. Here are two examples of Cures Within Reach repurposed therapies being used clinically in once deadly children's diseases and are both saving lives, and creating an estimated $40,000-$80,000 per patient per year in healthcare cost savings.
Cures Within Reach funded a generic drug repurposing research to produce the first and only effective treatment for the childhood blood disease Autoimmune Lymphoproliferative Syndrome (ALPS) at Children’s Hospital of Philadelphia. ALPS is considered an “orphan” disease, since it affects less than 200,000 Americans. Children with ALPS lead difficult lives. ALPS causes anemia and increased infections, so ALPS patients spend 5-10 days in the hospital every month getting transfusions and IV antibiotics. Though they have normal IQ, physical capabilities and communication skills, they are often years behind in school because of their chronic hospitalization.
Few of these children used to live beyond their twenties, but they are living longer and very normal lives now that they have a repurposed generic drug solution. Sirolimus, a safe drug already on the market, has created a low cost, low side effect treatment for these children. Children on sirolimus have been hospitalization-free since early 2006 and are often off all of their other high side effect medicines. This grant of less than US$300,000 transformed the lives of thousands of children in the US and around the world. It took less than 36 months, using an already existing drug, so no wasted time and money in further drug testing and approval issues.
The average ALPS patient’s medical bills used to exceed $100,000 per year. On the sirolimus drug repurposing regimen, no patient has been hospitalized for ALPS and the cost of medical care has been reduced by over $80,000 per patient per year! If all patients in the US with this disease were on Sirolimus, the total cost savings could exceed $60M per year.
Based on the success of repurposing sirolimus from ALPS, Cures Within Reach has funded additional sirolimus research to test this drug in 7 other rare and deadly pediatric auto-immune, including Evans disease, pediatric lupus, and idiopathic thrombocytopenia purpura. In the first three years of this pilot clinical, 50 children with one of these diseases have been treated with sirolimus. 42 subjects have gone into complete remission, 4 into partial remission, and 4 have not had success with this treatment. All 50 of these patients had failed all prior therapy, so an 85% success rate is a huge advance for these children.
In a similar Cures Within Reach success story, Drs. Berish Rubin and Sylvia Anderson study Familial Dysautonomia (FD) a disorder that affects the development and survival of the nervous system. In the summer of 2001, Dr. Rubin’s laboratory identified the genetic cause of FD is a defect in a gene that makes a protein called IKAP that is necessary for development and function of the nervous system. In 2005, Dr. Rubin’s lab discovered two compounds capable of increasing the amount of functional IKAP protein produced in these patients – one is a form of vitamin E and the other a chemical component of green tea, epigallocatechin gallate (EGCG). Afew years later the team found that vitamin A can further increase the production of functional IKAP. FD patients can take these vitamin A compounds along with the Vitamin E and EGCG. Then they made an every bigger discover in 2010 that two components of soy, genistein and daidzein, when combined with the other compounds, allow children with FD to produce 100 percent of the required IKAP protein! What this means, is that when these children take these compounds, which they can purchase affordably at the pharmacy, they can lead almost normal lives. Their nervous system will function as well as it would if they didn’t have the disease!
These discoveries, privately funded for less than $200,000 per year, have dramatically changed the lives of FD patients worldwide, and the families who cherish them. Much like the ALPS story above, these inexpensive and widely available FD treatments have significantly improved lives and reduced healthcare costs. Most children with untreated FD die before the age of 5, and during their years of life are hospitalized often and for long periods of time. Untreated FD healthcare costs average over US$100,000/year. Once on the regimen, their hospitalization use approaches normal, and their annual healthcare costs decrease to less than US$10,000 per year. The accumulated savings for these patients is in the tens of millions of dollars each year.
There are hundreds of similar stories waiting to benefit patients if the economic incentives can be created to support generic drug repurposing. These projects start with significant scientific justification, and often with clinical anecdotal support. They can be done quickly, safely and inexpensively, and because the drugs or nutriceuticals are already available, once the use is proven to help the disease and the data are published, physicians can begin to use the treatment to benefit patients and reduce healthcare costs.
3) Impact on human rights
There are a huge number of diseases that impact the poor and other in developing countries. These patients are often the last to benefit from de novo drug discovery because of the costs of the new treatments compared to the annual earnings of the patients. If these drugs do get to these patient groups it is often decades after they have reached developing countries.
Treatments created through a Generic Drug Repurposing SIB will be low cost and immediately available, even in developing countries, where generic drugs are often widely available. If they are not currently available, it is much easy to find a manufacturer and distributor for an inexpensive generic drug. And if the patients cannot afford the repurposed drug, the low cost makes government and/or NGO provision of the drug relatively inexpensive.
In conjunction with our UK partners Findacure and Numbers4Good, we have started the process in England to create the first Generic Drug Repurposing SIB for rare diseases. To support the SIB process, we have created an algorithm to help select the right kinds of repurposing projects, and we are developing a system to determine how the healthcare costs savings would be estimated. The National Health Service has partnered with us, assigning Dr. Harpreet Sood, Senior Fellow, to the Chairman and Chief Executive's Office of NHS, to work with us on this initiative. We have engaged Costello Medical Consulting to do the economic analysis of the impact of several new projects in diseases such as congenital hyperinsulinism, myelofibrosis, polycythemia vera, Wolfram’s Syndrome and others. We expect to complete these evaluations this year, and have the first Generic Drug Repurposing Social Impact Bond up and running in early 2017.
To support this global drug repurposing initiative, with funding from the Robert Wood Johnson Foundation, we created a web platform for the collection and review of repurposing research, called CureAccelerator™, and have funded 12 repurposing projects so far through CureAccelerator. CureAccelerator will be used to collect, review and help find funding for the Generic Drug Repurposing SIB Proposals from around the world.
In addition, we have completed two feasibility studies of drug repurposing Social Impact Bonds, one by the MaRS Centre for Impact Investing in Canada (funded by the Mindset Social Innovation Foundation) and one by Oliver Wyman consulting in the UK (done pro bono for our sister NGO Findacure.) We have government and impact investor interest in Canada and several EU countries, as well. Cures Within Reach has funded repurposing research in 7 countries so far, and has received requests for funding in many more. There are thousands of repurposing ideas in the minds of researchers and clinicians ready to be put to the test if we can create an economic engine to drive it forward.
The Open Source Pharma Foundation, an India-based NGO focused on creating new ways of developing drugs, is a supporter of this brief. Cures Within Reach is honored to be a supporter and collaborator of the Open Source Pharma Foundation brief, which describes the Open Source Pharma (OSP) concept inspired by the Linux model of IT operation. Adapted to tackling important public health challenges, OSP hopes to catalyze radical change to the way medical R&D can deliver better and more affordable innovation quicker and cheaper to patients. In brief, crowdsourced, computer-driven drug discovery; IT-enabled clinical trials with open data; and generics manufacture. Cures Within Reach is supporting OSP by leveraging our drug repurposing expertise and network.
We continue to engage with impact investors, government and non-government healthcare payers, repurposing research researchers and clinicians, the FDA, EMA and other regulators, to determine how best to create the SIB structure and the “pay for success” measures, how to determine which diseases are most likely to benefit from a repurposed treatment and yield healthcare savings, and how to insure that the repurposed therapy information can be effectively disseminated and used by physicians and patients. In the medium-term, we need to pilot several Generic Drug Repurposing SIB portfolios to test the algorithms, the success ratios, the patient impact and the actual cost savings. In the long-term, we need to manage the system so that it continues to grow, creating more and more opportunities for repurposing to create new treatments that save lives and save money.
We already had the ultimate goal of eventually reaching out to the UN and/or WHO and/or the World Bank to help us bring a global Generic Drug Repurposing Social Impact Bond solution to the world. We are well on our way, and the UN support at this stage could markedly accelerate the impact this could make improving and saving lives by solving disease issues, and helping the world reduce its ever growing healthcare costs. Together, we have the resources, the success stories, the opportunity, the infrastructure, the funding and the connections to make this work ASAP for patients that don't have time to wait.
Bibliography and References
Here is more information about Cures Within Reach, CureAccelerator and drug repurposing:
Overview video- https://www.youtube.com/watch?v=D0RXKVQSYxo
Link to speaking engagements- http://cureswithinreach.org/event-calendar/speaking-engagements
Media information: http://cureswithinreach.org/newsroom/media-coverage
Ashoka Fellow profile- https://www.ashoka.org/fellow/bruce-bloom
Blogpost about our work- https://www.ashoka.org/Chain_of-impact
Company Website- http://cureswithinreach.org
CureAccelerator™ Website- http://cureaccelerator.org
Food and Drug Administration: Frequently Asked Questions on Patents and Exclusivity; available at www.fda.gov/Drugs/DevelopmentApprovalProcess/ucm079031.htm#How%20long%20is%20exclusivity%20granted%20for?
2 Patent Docs: FDA Approval of Biologic Drugs under 505(b)(2) Expected to Increase; available at www.patentdocs.org/2011/10/fda-approval-of-biologics-under-505b2-expected-to-increase.html
3 D Radley, Off-label Prescribing Among Office-Based Physicians Archives of Internal Medicine 166 (9): 1021–1026 (2006)
4 FD NOW: Research Treatment Breakthroughs, available at www.fdnow.org/research/treatment-breakthroughs
5 N Ryan, et.al., Gabapentin for refractory chronic cough: a randomized, double-blind, placebo-controlled trial. The Lancet, V 380:9853, 1583–1589 (2012)
6 Roundtable on Translating Genomic-Based Research for Health; Board on Health Sciences Policy; Institute of Medicine. Drug Repurposing and Repositioning: Workshop Summary. Washington (DC): National Academies Press (2014)
7 D Teachey, R Greiner, A Seif, et.al. Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. Br J Haematol. 145(1):101-6, (2009)