❚ REGENERATIVE In Vivo Pharma intelligence | Curative Regenerative : Preparing Health Care Systems For The Coming Wave

We may be at the dawn of a new era of curative regenerative , but their inherent nature may create barriers to adoption. The Alliance for Regenerative Medicine frames the opportunities and challenges for the industry, arguing that policy makers must begin to understand 1 the ways that these therapies represent value for money. Shutterstock: Lightspring Shutterstock:

BY FARAZ ALI, TED SLOCOMB mily Whitehead was diag- disease go into complete remission. AND MICHAEL WERNER nosed with an aggressive Additional companies using similar form of cancer called acute approaches for other malignancies have More than 700 companies are working lymphoblastic leukemia reported exciting early results, prompting on new gene, cell and tissue (ALL) at the tender age of many to dare speak of a “cure” for cancer. engineering therapies that have the potential for profound and durable 5E in 2010. She had relapsed twice after In fact, when US Vice President Joe Biden responses in patients with a diverse chemotherapy and was out of options called for a “moonshot” effort to “end array of serious and costly conditions, and near death when she was treated cancer as we know it,” he did so fully many of which lack current treatments. with an experimental chimeric antigen aware of the promise of such gene and receptor T cell (CAR-T) gene cell therapies already under development The health care market is grappling at Children’s Hospital of Philadelphia and rapidly approaching the marketplace. with ways to articulate and assess the (CHOP) that saved her life. Emily’s story But treatments for cancer are only the value of these potential curative was published on the front page of the tip of the iceberg. treatments, some of which may be New York Times in December 2012. We are at the cusp of a global revolu- administered only once or a few times. Three years later at the American Soci- tion in medicine. Medical researchers ety of Annual Meeting, phar- and product developers are now poised There are a number of proposed maceutical giant Novartis AG revealed to bring forward new gene, cell and tis- alternative reimbursement and that Emily was not alone. More than 90% sue engineering therapies that hold out fnancing models to address the of patients with relapsed refractory ALL the promise of profound and durable potential uncertainty and economic treated with the same CAR-T therapy – responses – often with just a single treat- disincentives that may be associated being developed in a large multi-site ment – for patients with a diverse array with curative therapies. clinical study including CHOP that is of serious and costly conditions, many of now sponsored by Novartis – had their which lack current treatments.

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The shared mission of these tech- potential of the regenerative medicine beginning to become familiar with the nologies is to establish – or restore – the industry. (Also see “Gene Therapies: technologies involved and with the op- healthy functioning of human cells Waiting To Emerge From The Bottle” – portunities and challenges facing their in patients with cellular dysfunction. Scrip, September 6, 2016.) After decades introduction to the market. Some of the new technologies also of work – and some noteworthy early represent the highest form of personal- setbacks – the fields of cell therapy, gene The Sovaldi Efect ized medicine, requiring the treatment therapy, and broader One curative therapy outside the regenera- to be highly tailored and specific to the regenerative medicine are progressing tive medicine area – Sovaldi (sofosbuvir) patient’s genetic background, and often through the clinic with great promise. developed by Gilead Sciences Inc. for utilizing the patient’s own cells to create As of mid-2016, we identified more than hepatitis C – has been in global headlines the necessary therapies. The term “regen- 700 companies working on regenerative in recent years. Most of the headlines have erative medicine” also includes exciting medicines, and 728 clinical trials ongo- been negative and have focused primarily developments in the use of gene editing ing for such therapies, with 66 potential on issues of price, pharmaceutical com- technologies to replace or correct genetic therapies already in active Phase III (or pany profits, health care costs and patient material with unprecedented precision. equivalent) late-stage clinical trials, access. Noticeably less media – and po- A handful of regenerative medicine almost doubling the count over the previ- litical – attention has been devoted to the products have been approved in various ous year. (See Exhibit 2.) clinical efficacy of Sovaldi or the fact that countries around the world; many other Regenerative medicines represent as a curative therapy it may also be cost- new therapies are nearing the market, a wave of innovation coming to the effective because of the prevention of the currently in mid- to late-stage clinical shores of our health care system that costly long-term consequences associated trials. We expect that several will enter is approaching much faster than most with hepatitis C. the market within the next few years. realize. With the assistance of groups like Without debating the merits of the (See Exhibit 1.) the Alliance for Regenerative Medicine case here, the Sovaldi experience has un- These diverse examples are just a (ARM, www.alliancerm.org), policy mak- doubtedly helped pour fuel on a broader glimpse of the depth, breadth and ers, payers, and patients are fire raging against biopharmaceutical

Exhibit 1 2 On- Or Near-Market Regenerative Medicines

COMPANY/TREATMENT INDICATION STATUS

Lipoprotein lipase defciency Approved by the EMA in 2012. First approval of a uniQure/Glybera (LPLD), a rare and ofen fatal fat using adeno-associated viruses (AAVs) metabolism disorder

Approved by the FDA in 2015. First approval of a gene therapy Amgen/Imlygic Melanoma based on technology

Repair corneas and restore sight in Approved by the EMA in 2015. First approval of a tissue Chiesi/Holoclar patients with burns to the eyes engineered medicinal product derived from stem cells

GlaxoSmithKline/ Specifc form of severe combined Approved by the EMA in 2016. First approval of a gene therapy Strimvelis immunodefciency (ADA-SCID) based on ex vivo autologous retrovirus technology

Mesoblast & JCR Acute graf-versus-host disease in Pharmaceuticals Co. Ltd./ Launched in Japan Feb. 2016 children and adults TEMCELL

Gene therapy using AAV for a form Spark Therapeutics/ of inherited blindness called Leber’s FDA submittal 2016; potential approval 2017 SPK-RPE65 congenital amaurosis (LCA)

CAR-T cell therapy for advanced Kite Pharma/KTE-C19 BLA fling early 2017; commercial launch anticipated 2017 non-Hodgkin lymphoma

CAR-T technology for relapsed/ Novartis/CTL019 FDA submittal 2016; potential approval 2017 refractory pediatric ALL

SOURCE: Alliance for Regenerative Medicine

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Exhibit 2 There have been commendable recent Gene And Cell Therapy Clinical Trials efforts by various groups to attempt to develop new frameworks to evaluate the value of biopharmaceutical products. Gene And Cellular Therapies And Other Such efforts include the American So- Regenerative Medicine Products: ciety of Clinical (ASCO) Value Framework, the Institute for Clinical CLINICAL TRIALS and Economic Review (ICER) Value Ph. I: 223 +40% Assessment Framework and the Memo- rial Sloan Kettering Cancer Center’s Ph.II: 439 of current clinical 728 DrugAbacus project, as well as numerous { Ph.III:66 trials are in oncology tools developed by for-profit firms. (Also see “Drug Pricing: With “Value” Debate In Full Swing, ICER’s Influence Grows” – In 12% Vivo, November 2, 2016.) However, even of current clinical trials these attempts have been criticized and are in cardiovascular are at odds with each other, and none of them formally address unique attributes SOURCE: Alliance for Regenerative Medicine of potentially curative therapies that should contribute to an appropriate as- sessment of their value. drug pricing and the growing costs of é How can innovators in the biopharma- We therefore lack a common vocabu- health care. In doing so, it may have also ceutical industry be better partners to lary even to begin a conversation about unintentionally tainted the optimism and the stakeholders involved? the value of curative therapies. And yet, excitement that should be attached to the it is critically important for policy makers development of curative therapies, and This article – as well as planned subse- to begin to understand all the ways in caused policy makers to fear that the new quent papers – is an early effort of ARM which potentially curative regenerative 3 era of regenerative medicine represents to help frame the opportunities and the medicine therapies may represent value an era of Sovaldi-sized problems. challenges of potentially curative gene for money. We introduce here a simple We are concerned that political rhetoric and cell therapies and to spark a con- framework with four distinct categories may turn into broad policy and legislation versation about specific policy proposals to describe the potential value of regen- that may fail to recognize the uniquely high that will benefit patients, the health care erative medicines. (See Exhibit 3.) value of curative regenerative medicines system and ultimately, society. and that may instead inadvertently create 1. Clinical Impact: In part because of the significant impediments to their funding, What Is a Pound of Cure Worth? nature of the technologies involved, development and adoption. Many stakeholders will intuitively ap- such therapies may have a transforma- Against this backdrop, it is therefore preciate the uniquely high value of tive impact on the underlying diseases critical for major stakeholders in the emer- potentially curative therapies. However, at many levels. The impact of curative gence of curative regenerative medicines to any detailed discussion about the value of regenerative medicines may be felt in engage on the following key issues: biopharmaceutical innovation is fraught different ways: with challenges. This is true for so-called é What lessons can the health care system conventional therapies that are admin- é Quality of the effect. Conventional learn from past experience with other istered – and paid for – chronically over therapies often manage the symptoms curative therapies such as Sovaldi? time (potentially over the lifetime of a of the disease, whereas regenerative patient). It is also equally if not more chal- medicines have unique mechanisms é In what ways will the coming wave of lenging when trying to articulate the value of action that may target the underly- regenerative medicines be different of potential curative therapies that may ing cause of the disease. For example, from Sovaldi? be administered only once or a few times. many gene therapies directly target Part of what makes such a discussion the underlying genetic defect lead- é How should the value of curative challenging is that there is no universally ing to the disease in a manner that therapies be measured and benefits accepted or standardized methodology other therapeutic modalities cannot, distributed among major stakeholders? to assess the value of biopharmaceutical enabling treatment of previously un- innovation across advanced economies treatable conditions. é Do health care systems around the with nationalized single-payer health care globe need to change their policies to systems, or even across public and private é Magnitude of the effect. As a result of accommodate curative therapies and payers within fragmented multi-payer their mechanism of action, curative if so, how? health care systems like the US. therapies may not only halt but even

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Exhibit 3 Curative Regenerative Medicine Benefts

CLINICAL HEALTH-RELATED QUALITY OF LIFE ì$GGUHVVXQGHUO\LQJFDXVHRIGLVHDVH ì,PSURYHSDWLHQWUHSRUWHGRXWFRPHV ì6WDELOL]HRUUHYHUVHRUJDQG\VIXQFWLRQ ì,PSURYHRYHUDOOVHQVHRISK\VLFDODQG SV\FKRORJLFDOZHOOEHLQJ ì+DOWGLVHDVHSURJUHVVLRQ ì(OLPLQDWHRUUHGXFHQHHGIRUFKURQLF ì'HFUHDVHPRUELGLW\ therapy ì,QFUHDVHVXUYLYDO ì,PSURYHIXQFWLRQDODELOLWLHV BENEFITS HEALTH CARE COSTS SOCIETAL ì$YHUWIXWXUHFRVWVRIVWDQGDUGRIFDUH ì,QFUHDVHZRUNSURGXFWLYLW\ including chronic therapies ì5HGXFHDEVHQWHHLVP ì$YHUWFRVWVRIIXWXUHFRPSOLFDWLRQV of disease ì)LQGHPSOR\PHQWDQGFRQWULEXWHWR IDPLO\DQGVRFLHW\ ì$YHUWIXWXUHFRVWVRIQRQFRPSOLDQFH and waste ì$YHUWVHFRQGDU\LPSDFWRQFDUHJLYHUV

4 SOURCE: Alliance for Regenerative Medicine

reverse disease manifestations, that improvements in patient QOL are to be ing hospitalizations, especially for could significantly decrease disease expected, as has been already demon- diseases without existing therapies. morbidity and extend lifespan. strated in other curative settings (e.g., transplantation). é Eliminating or replacing the direct costs é Duration of the effect. Conventional of existing chronically administered therapies often need to be administered é Patient QOL may benefit from the ability therapies. chronically to be effective. Conversely, to discontinue chronically administered curative therapies often aim to treat the therapies that are often inconvenient é Eliminating the downstream costs as- patient with a single intervention or a and may require frequent travel to spe- sociated with the side effects of existing series of interventions with long-term cialist locations. chronically administered therapies. and even potentially lifetime impact (a phenomenon sometimes referred to as é Improvements in QOL may not be re- é Eliminating the significant costs of non- “one and done”). stricted to patients, but may also extend compliance with conventional thera- to other caregivers involved, depending pies, as well as the costs of programs 2. Quality of Life: Increasingly important on the disease. to encourage compliance. to patients, physicians and payers is not just extension of life, but also improve- 3. Health Care System Cost Savings: Based on ARM analysis, the current ment in objective health-related quality Curative therapies have the potential pipeline of regenerative medicines as of life (HR-QOL) measures and other to offset significant costs to the health described earlier are indeed addressing patient-reported outcomes (PROs). care system. The impact of curative some of the costliest disease areas and The impact of curative regenerative regenerative medicines may be felt in conditions currently driving US health medicines may be felt in different ways: different ways: care costs. (See Exhibit 4.)

é If curative therapies live up to the é Averting the costs associated with the 4. Societal Benefits: Societal benefits are expectations for high clinical impact downstream complications of disease often underappreciated in the evalua- as described earlier, commensurate progression and complications includ- tion of the value of new therapies. The

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Exhibit 4 impact of curative therapies may be felt Selection Of Conditions Targeted By Cell And Gene Therapies in different ways:

é Increased productivity and reduced ESTIMATED workplace absenteeism for patients. ANNUAL COST OF SELECTION OF INDICATIONS DISEASE AREA TO TARGETED BY CELL AND GENE é Employment for patients who previ- DISEASE AREA US ECONOMY THERAPIES ously have not been able to work.

é Reduced burden on caregivers of Wound care, neuropathic pain, stress patients. urinary incontinence, , Musculoskeletal >$874bn cartilage defects, spinal disorders, While the broad categories of value avascular necrosis, bone fracture and described are not unique to regenerative other rare genetic muscle disorders medicines, what is unique is the incre- mental benefit expected over and above what can be achieved with conventional therapies across a patient’s lifetime, and the potential ability to generate such Congestive heart failure, ischemic long-term benefit with a single or a limited stroke, critical limb ischemia, ischemic Cardiovascular >$316bn number of applications of therapy. heart disease, peripheral artery There is a slowly growing but encour- disease aging body of evidence that some payers and health technology assessment bodies globally are beginning to recognize the Spinal cord injury, ALD, multiple potential value of regenerative medicine, sclerosis, Friedreich’s ataxia, neuro- and the need for change: 5 Central Nervous muscular disorders and various >$245bn System (CNS) neurological conditions including é Private and public payers interviewed Alzheimer’s disease, Parkinson’s for a study commissioned by the Cali- disease, Huntington’s disease, etc. fornia Institute of Regenerative Medi- cine (CIRM) in 2009 acknowledged that potentially curative therapies would be paid for in the near term Inherited eye diseases, blindness, Ophthalmological >$139bn with premium increases, “although corneal transplantation the premiums would be reduced if the curative treatments generate long-term cost savings.” Renal cell carcinoma, mesothelioma,

prostate cancer, head and neck cancer, é In the UK, the field of regenerative nasopharyngeal cancer, non-small cell medicine was elevated to one of “Eight lung cancer, ovarian cancer, leukemia, Great Technologies” that will propel Oncology >$124bn lymphoma, skin cancer, brain cancer, future growth. As part of an assess- hematologic malignancy, graf vs. host ment of the impact of regenerative disease, cytomegalovirus infection due medicines in 2013, the UK government to malignancy also expressed the need “to devise suitable models that give appropriate consideration to the long-term savings sometimes offered by high up-front cost [regenerative medicine] treat- Inherited Blood Sickle cell disease, hemophilia A & B, ments.” >$7bn Disorders beta thalassemia é The UK’s National Institute for Clini- cal Excellence (NICE) health technol- ogy assessment (HTA) organization SOURCE: Alliance for Regenerative Medicine published in 2016 a formal review of its models as applied to potentially

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curative cell or gene therapies, and é For some diseases, it may be decades PRODUCT COMPLEXITY determined that “where there is a before we know if the clinical impact é Some regenerative medicines – particu- combination of great uncertainty but has been as profound and as durable larly ex vivo autologous therapies that in- potentially very substantial patient as hoped for at the time of regulatory volve the extraction and manipulation of benefits, innovative payment method- approval. patients’ own cells – are highly complex ologies need to be developed to man- and involve different procedures sepa- age and share risk to facilitate timely é Stakeholders therefore may feel they rated over time, care settings and even patient access while the evidence is have no guarantee the products will live geography, which may challenge health immature.” up to their promise, which may encour- care systems that are set up around more age a “wait and see” approach to adop- conventional therapies. é A 2016 publication by Eric Faulkner tion, to the detriment of patients. et al. provides summaries of surveys é New technologies may cut across tradi- of US managed care payers and physi- ECONOMIC DISINCENTIVES tional boundaries. Something that was cians, illustrating that roughly 30% é There is an inherent disconnect be- previously not considered a product or think regenerative medicines will be tween the timing of payment for poten- device (e.g., a patient’s own cells) may transformative and about 60% felt that tially one-time curative medicines and become so with specific manipulation. a regenerative medicine therapy that the savings to the health care system There may not be adequate frameworks permanently cured a disease could that may result, but that may only be to value and reimburse such therapies. merit a significant (>50%) increase in realized over decades after the therapy payment over existing alternatives. is administered. Current insurance é Payment codes may simply not ex- coverage policies, mechanisms and ist to represent payment for the full Although these are encouraging economics are not designed to consider spectrum of product, materials and early signals, recent history suggests the benefits of particular interventions processes used to deliver a cell or gene that stakeholders may not automatically over a long period of time. Most health therapy, and creating and introducing understand all the sources of value asso- coverage policies address the costs of new codes may be more difficult than ciated with biopharmaceutical products, patients on an annual basis and are for more conventional medicines. and that they tend to focus on price, cost not structured to take into account 6 and budget impact. It is therefore critical offsetting benefits of specific therapies REIMBURSEMENT PARADIGMS that regenerative medicine innovators that are realized outside of this annual é Health care systems are generally not engage in the public discourse on this window. This concern is exacerbated in configured to pay for new products in topic and help inform payers and policy more fragmented health care systems, a manner other than a price per unit makers. as is the case in the US, where patients (vial, treatment, procedure), exac- move around between plans over time erbating the divergence in timing of Even If You Build It, and may only be with any given plan product cost and benefits generated 7KH\0D\1RW&RPH on average for two to three years. by the product for one-time therapies. Acknowledging the potential value of curative regenerative medicines is an é Some regenerative medicines may rep- é There may be legal or statutory bar- important first step. However, it is equally resent cures for serious and progres- riers – such as specific coverage or important to acknowledge the potential sive diseases such as congestive heart payment rules set by CMS – that pose challenges such therapies may pose to failure, Alzheimer’s disease or diabetes reimbursement challenges for regen- the current health care system, which that affect large populations waiting erative medicine products. may in turn introduce undesirable barri- for better alternatives. Approval of ers to their adoption to the detriment of such therapies may create extreme While no single barrier on its own patients in need. near-term budget impact issues for may be problematic, the totality of these A preliminary assessment by ARM has public and private payers driven by considerations may create challenges identified several potential challenges high and acute demand that cannot for stakeholders and policy makers, that fall under four categories: be covered by temporary, incremental impeding coverage, coding, valuation, premium increases. reimbursement and, ultimately, adoption UNCERTAINTY of regenerative medicines. é While gene and cell therapies have been é The US health care system is already under development for three decades shifting a higher burden of cost-sharing 7RZDUGD1HZ3DUDGLJP and have been studied in thousands onto patients in the form of higher There is a growing crescendo of proposed of patients, we must acknowledge that deductibles and co-pays for their thera- solutions to address some of the potential their successful clinical application is pies. Patient co-pays that are set as a barriers associated with curative regen- still a fairly recent phenomenon. Regula- percentage of potentially high one-time erative medicines. (See Exhibit 5.) Based tory approvals are sparse and real-world price may be prohibitively expensive for on our early assessment, most proposals experience is limited. patients seeking curative therapies. focus on alternative reimbursement and/

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or financing models, and are intended Exhibit 5 to address the potential uncertainty and economic disincentives that may be as- Alternative Models sociated with curative therapies.

é Risk-sharing agreements: An agree- $OWHUQDWLYH5HLPEXUVHPHQW Alternative Financing ment between payers and innovators Models Models to ensure that payers’ exposure is lim- ited or eliminated if a patient fails to Primarly intended Primarly intended respond to an expensive regenerative to address uncertainty to address afordability medicine.

é Value-based contracting: Also known as “pay-for-performance,” an Cost Sharing Cure Pools Supplier Credit $JUHHPHQWV (for payers) agreement between payers and innova- Reinsurance tors that ties the amount of payment Risk Sharing Bonds provided to the degree of value realized $JUHHPHQWV License Fee (clinical, economic or other). (for governments) Annuities Value-Based &RQVXPHU+HDOWK é Annuities: An agreement between 3D\PHQWV Care Loans the innovator and the payer to spread payments over time to reduce the cost (for individuals) intensity of potentially expensive one-and-done curative therapies. This could be combined with risk-sharing agreements or value-based contracting SOURCE: Alliance for Regenerative Medicine as described to also include a perfor- 7 mance component. incurred by patients who have to travel Reason For Hope é Re-insurance: A financial arrange- to centers of excellence for highly Although most discussion of curative ment that limits insurers exposure to specialized curative therapies and that therapies today focuses on the experience the risk of an expected volume of high- may involve long stays for families near with Sovaldi, less attention is paid to the cost procedures. Re-insurance was such centers. fact that the global health care system successfully introduced and adopted has already been working with curative to address high-cost solid organ and There has been a tendency to jump therapies for more than three decades in stem cell transplantation procedures. to a particular solution from this list of the form of solid organ and stem cell trans- proposals as the silver bullet that will plantation procedures. These procedures é Payer financing: Lease-like financing address all or most of the potential bar- were – and are still today – among the most provided by makers of expensive medi- riers associated with regenerative medi- expensive medical interventions (a Milli- cal imaging equipment to hospitals. cines. Pay-for-performance and annuity man research report from 2014 estimated Financial intermediaries could provide models appear to generate particularly average billed charges for heart transplants similar loans to payers to address high levels of support. We believe that and allogeneic stem cell transplants at situations where there is an issue of it is still too early – and ultimately may around $1 million per procedure). At the near-term but temporary budget afford- not be helpful – to try to pick any one time of their introduction, there was a ability in response to the approval of a proposed solution. The health care sys- considerable amount of technological and new cure. tem may need to be prepared to adopt clinical uncertainty related to utilization multiple solutions that are tailored to and long-term outcomes. There was also é Consumer health care loans: Mort- the specific attributes of the disease and concern then about the ability of the health gage-like financing provided by fi- regenerative medicines involved, and to care system to absorb the costs of these nancial intermediaries that allow the preferences of the local health care procedures. Re-insurance was success- consumers to take out loans to finance system. In addition, what is still missing fully introduced as an alternative model large co-payments or possibly to pay is a comprehensive inventory of such so- to address issues related to uncertainty outright for cures in situations where lutions, supported by rigorous analysis, and affordability. This pairing of medical there is inadequate coverage. modeling and weighing of the pros and and financial innovation has allowed the cons from the perspective of different field of transplantation to flourish over the é Co-payment reform: Reconsideration stakeholders. This work is critical, and decades and to benefit millions of patients of coverage for out-of-pocket expenses has been prioritized by ARM and others. across the globe facing life-threatening

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conditions. There are many lessons to be ❚ ABOUT ARM learned from this experience that may have parallel applications to the coming wave of The Alliance for Regenerative Medicine is the largest single advocacy regenerative medicines. organization dedicated to the emerging feld of regenerative medicine. ARM was established to support a dialog between the developers of Conclusions transformational new therapies and policy makers at all levels, with Regenerative medicine, including cell and the goal of increasing awareness about these new therapies and their gene therapy and other similar advanced potential benefts and costs, as well as generating and evaluating therapy products have already begun to potential policy solutions to appropriately enable access for patients demonstrate the potential to deliver on that address the needs of all key stakeholders. their promise to treat or cure a range of diseases. The pipeline of such therapies ARM encourages a productive discussion on these critical topics with is robust. The potential social, clinical patients, public and private payers and other stakeholders as we work and economic value of these treatments together to identify and promote solutions that will ensure potentially is significant and may require a serious life-transforming technologies become widely accessible and adopted rethink of the current focus on costs and as and when their promise is realized. price. It is critical to ensure successful de- velopment of these products by creating a ARM also partners with representatives from other organizations reimbursement environment that rewards engaged in multi-stakeholder initiatives to prepare the health care innovation when value is demonstrated or system for curative and/or regenerative medicines. (See Exhibit 1.) can be reasonably anticipated. These include the Biotechnology Innovation Organization (BIO), the Getting there will not be straightfor- International Society for Cellular Therapy (ISCT), the National Marrow ward. There are complex issues to be Donor Program (NMDP), the NEW Drug Development ParadIGms (NEW- discussed, barriers to be confronted, DIGS) program at the Massachusetts Institute of Technology (MIT), the solutions to be considered and even some American and European Societies for Gene and Cell Therapy (ASGCT societal choices to be made. This will and ESGCT), the International Society for Stem Cell Research (ISSCR), likely require a uniquely broad coalition and the Tissue Engineering and Regenerative Medicine International 8 of diverse stakeholders working together Society (TERMIS), among others. proactively and productively years in ad- vance of this wave of innovation. This is the first of a series of papers pre- Multiple Regenerative Medicine Stakeholders sented by ARM and its member organiza- tions in the US and EU that are intended to support the necessary dialogue. (See side- bar, “About ARM.”) Subsequent reports Payers and Patients, will describe the potential reimbursement Health Tech )DPLOLHVDQG barriers as well as assess the potential $VVHVVPHQW Advocacy Orgs Orgs solutions to the challenges described in this article with far more rigor. This work Physicians, will culminate in specific policy propos- Hospital als and recommendations for legislative Regulatory CURATIVE 6\VWHPVDQG Agencies REGENERATIVE change that may be necessary to unlock THERAPIES Medical Societies the full potential of curative regenerative Multi-Stakeholder medicines. Society – and innumerable Dialogue patients like Emily Whitehead in need of Health life-saving regenerative medicines – will (FRQRPLVWV Participants Policy Makers and judge us on our success. $FDGHPLD IV004955

Regenerative Financial Faraz Ali ([email protected]) is Chief Medicine Services and Business Officer, REGENXBIO, Ted Slo- Innovators and Reinsurance Trade Orgs &RPSDQLHV comb ([email protected]) is VP, Commercial Planning, Audentes Thera- peutics and Michael Werner (michael. [email protected]) is Executive Director of the Alliance for Regenerative Medicine SOURCE: Alliance for Regenerative Medicine and a Partner at Holland & Knight LLP.

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