WALPOLE , MA - AUGUST 6: Estelle Lemieux, a 21-month-old with spinal muscular atrophy, practices ... [+] using her new wheelchair outside of her home in Walpole, MA on Aug. 6, 2019. Estelle will be getting a treatment of Zolgensma after her insurer, Aetna, decided to cover the $2.1 million drug. (Photo by Jessica Rinaldi/The Boston Globe via Getty Images)
The promise of gene therapy is to cure diseases associated with faulty or missing genes. Theres enormous potential. Just this month, at the annual American Society of Hematology meeting, it was shown that gene therapy stops bleeding in hemophilia. Researchers reported that a single injection of a viral-mediated gene therapy vector decreases the bleeding rate among patients with Factor IX-related hemophilia B by 91% over a 6 month period.
Ideally, gene therapies address the root causes of disease with a single curative dose. If they can replace a lifetime of expensive maintenance treatments this may lead to cost savings in the long run. Yet, the high upfront costs, uncertainty surrounding long-term durability, and adverse events have led to some concerns among payers and regulators.
Pharmaceutical firms deploy multiple approaches to pursuing curative gene therapy, including:
These approaches build on advances in basic science. Companies involved in gene therapy research and development include mid-size and large firms. Among other large pharmaceutical firms, Bayer is establishing a cell and gene therapy platform within its pharmaceuticals division. The company aims to deploy the platform in as many indications as possible.
Novel drug development is invariably a risky venture. The issue of risk is further amplified in gene therapy. Promising therapies face unexpected challenges. For example, in a surprise decision this fall, the Food and Drug Administration (FDA) rejected BioMarins license application for its gene therapy to treat severe hemophilia A. According to the FDA, valoctocogene roxaparvovec gene therapy, is not ready for approval in its present form. The FDA changed its data requirements for the application. The agency is now requesting that the sponsor BioMarin provide two years of data from the companys ongoing Phase 3 study of the therapy.
While development challenges will persist, payment hurdles may be equally difficult to overcome. Should many of the gene therapies in the pipeline be approved in the coming decade the budgetary impact burden on payers could become overwhelming. Payer concerns stem in part from there being hundreds of gene therapies in clinical development,across a wide range of therapeutic categories, including among others, cardiovascular disease, Parkinsons, various inherited disorders, different types of cancer, viruses such as HIV, and blood diseases like sickle cell anemia.
The churn or turnover at U.S. insurers - as beneficiaries frequently switch plans - lowers the potential return on investment for payers. So, being saddled with high upfront costs without necessarily experiencing the downstream long-term benefits of gene therapies is a considerable problem for which a structural solution has not yet been found.
The payer assumes all the risk with fixed, static pricing. And, the payer isnt able to properly assess that risk, given that clinical development of gene therapies has, thus far, mostly included only very small numbers of patients. Therefore, the real-world benefits and risks remain unclear at the time of approval. Clearly, given the uncertainties regarding long-term durability of gene therapies as well as the potential for toxicity and other adverse effects to patients, a dynamic pricing structure is not only desirable but essentially required for these treatments.
In what appear to be harbingers of new ways to finance gene therapies and potentially turn fortunes around of therapies lagging in uptake, drug manufacturers are offering - and in some cases payers have been amenable to - indication-specific pricing arrangements, value-based contracts, and installment plans.
For example, in 2018, the FDA approved the gene therapy Luxturna. This treatment holds the promise to restore functional vision to the blind. The sponsor, Spark Therapeutics, set its products price at $425,000 per eye. Harvard Pilgrim entered into a unique outcomes-based contract with Spark Therapeutics. In the deal, Harvard Pilgrim pays for Luxturna, but gets certain refunds if the treatment wears off after a defined period of time. The full details of the contract are confidential. What is known, however, is that because of federal regulations, known as Medicaid best price rules, the maximum refund cannot exceed 23.1%, or the amount Spark Therapeutics is required to offer Medicaid programs. Spark Therapeutics did request that the Centers for Medicare and Medicaid Services (CMS) offer ways to work around the Medicaid best price requirement, in order for it to be able to accept installment payments and provide insurers deeper refunds or rebates in case the product doesnt meet certain targets.
Novartis Gene Therapies has been working closely with payers to create five-year outcomes-based agreements and novel pay-over-time options for the Zolgensma therapy, indicated for spinal muscular atrophy. The sponsor asserts that the treatment is cost-effective, even when priced at $2.125 million per patient. The installment plans would spread out payments over five years. In addition, the sponsor would offer a refund if a patient dies or the treatment otherwise fails within that period.The current alternative to Zolgensma is BiogensSpinraza, which patients take for the duration of their lifetime. The costs of Spinraza are approximately $4 million over a 10-year span.
In 2019, BluebirdBio told investors it was seeking value-based installment plan contracts to reimburse its sickle cell anemia product LentiGlobin for transfusion-dependent beta-thalassemia. The installments would be paid over a period of up to five years.
After an initial charge, Bluebird Bio would only get reimbursed if the one-time infusion benefits patients. This implies that up to 80% of the cost of LentiGlobin would only be made if there is treatment success. And this success would then be measured and tracked in patient registries maintained by payers.
As part of its contracting preparations, Bluebird Bio has sought ways to bypass Medicaid best price rules; for example, waivers to establish an exemption. The company has also pursued a resolution to the issue of portability - when patients change insurers - by way of a mutual recognition strategy across payers.
But, now the FDA wants Bluebird Bio to provide additional information on the manufacturing process it will use as it transitions the product, LentiGlobin, from clinical trials to commercial production. This will push back the timing of execution of contracts until LentiGlobin gets approved by FDA, which may not be until 2022 or later.
Across the various contract constructs described, payments can be administered in different ways that are not mutually exclusive:
Reimbursement of pharmaceutical products generally happens on a per-unit basis, which spreads out costs over years. But, the cost of a gene therapy is much more concentrated, possibly all upfront in a single payment. Such high upfront one-time costs make it harder for payers to underwrite the risk of full payment for one therapy, let alone the entire range of gene therapies that may be coming to market shortly. Therefore, a combination of installment plans and value-based contracting arrangements will likely be the wave of the future for gene therapy reimbursement.
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- Affinia Therapeutics Announces Addition of Gene Therapy Scientific and Medical Experts to Leadership Team to Advance Novel Gene Therapy Platform and... - February 17th, 2021
- Avance Biosciences Expanding Houston Campus in Support of Cell and Gene Therapy Drug Development - BioSpace - February 17th, 2021
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- Beti-Cel Gene Therapy Frees Patients With Beta-Thalassemia From Red Blood Cell Transfusions - OncLive - February 17th, 2021
- Forge Biologics Receives FDA Fast Track, Orphan Drug, and Rare Pediatric Disease Designations for FBX-101 Gene Therapy for Patients with Krabbe... - February 17th, 2021
- CDMO Vigene plots cell and gene therapy manufacturing expansion, adding 245 new jobs along the way - FiercePharma - February 17th, 2021
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- Genethon and WhiteLab Genomics Join Forces to Enhance Gene Therapy Through Artificial Intelligence - BioSpace - February 17th, 2021
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- The Europe cell and gene therapy market by revenue is expected to grow at a CAGR of over 23% during the period 20212026 - GlobeNewswire - February 11th, 2021
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- Dyno Therapeutics Announces Publication in Nature Biotechnology Demonstrating Use of Artificial Intelligence to Generate Unprecedented Diversity of... - February 11th, 2021
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- Taysha Gene Therapies Announces Participation in Upcoming Investor Healthcare Conferences - Yahoo Finance - February 11th, 2021
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- Amicus Therapeutics Presents Positive Preclinical Fabry Disease Gene Therapy Data at the 17th Annual WORLDSymposium 2021 - GlobeNewswire - February 11th, 2021
- Paragon Biosciences Expands Cell And Gene Therapy Platform - Contract Pharma - February 11th, 2021
- FDA Clears IND Application for Passage Bio's Gene Therapy Candidate PBKR03 for Treatment of Patients with Early Infantile Krabbe Disease, A Rare... - February 11th, 2021
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- AGTC Executives Awarded First Place in the BioProcess International Reader's Choice Awards, Cell & Gene Therapies Category - GlobeNewswire - February 7th, 2021
- Retinal Gene Therapy Market: Advent of High-end Technologies to Support Development of the Market - BioSpace - February 7th, 2021
- Sio Gene Therapies Announces Receipt of $11.6 Million from Closing of the Sale of Arvelle Therapeutics - BioSpace - February 7th, 2021
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- Sio Gene Therapies Announces First Patient Dosed in Clinical Trial of AXO-AAV-GM2 in Patients with Tay-Sachs and Sandhoff Disease (GM2 Gangliosidosis)... - February 7th, 2021
- Abeona Therapeutics Announces Clinical Investigator Webinar to Review ABO-102 and ABO-101 Clinical Data Presented at the 17th Annual WORLDSymposium -... - February 7th, 2021
- Decibel and Catalent Sign Development and Manufacturing Agreement for Dual-Vector Gene Therapy for the Treatment of Congenital Hearing Loss - Yahoo... - February 7th, 2021
- Meeting the commercialization challenge of a surging gene and cell therapy market - FierceBiotech - February 7th, 2021
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- Adverum Biotechnologies Announces Publication of Preclinical Long-Term Safety Data on ADVM-022 IVT Gene Therapy - BioSpace - February 7th, 2021
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- After reeling back a gene therapy from Sanofi, a North Carolina upstart bags enough money to do something about it - Endpoints News - December 17th, 2020
- Gene Therapy in One Eye Improves Vision in Both Eyes - The Scientist - December 17th, 2020
- After leaving Wall Street to launch a gene therapy upstart, Rachel McMinn nabs $115M to drive her first candidate to the clinic - Endpoints News - December 17th, 2020
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- Passage Bio Invests In Gene Therapy Manufacturing R&D Site - Contract Pharma - December 17th, 2020
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- They thought their gene therapy failed. Instead, it spawned a medical mystery - Endpoints News - December 17th, 2020
- Health Canada approves Zolgensma, the one-time gene therapy for pediatric patients with spinal muscular atrophy (SMA) - Canada NewsWire - December 17th, 2020
- Gene Therapy Injection in One Eye Improves Vision in Both - Technology Networks - December 17th, 2020
- Locanabio Raises $100 Million to Advance RNA-Targeted Gene Therapies - BioSpace - December 17th, 2020
- Worldwide Gene Therapy Industry to 2025 - Cancer is Expected to Hold Significant Market Share in the Indication Segment - ResearchAndMarkets.com -... - December 17th, 2020
- Taysha Gene Therapies Set to Join Russell 2000 Index on December 21, 2020 - Business Wire - December 17th, 2020
- Rare Disease Gene Therapy Market: Increasing cases of genetic diseases to drive the market - BioSpace - December 17th, 2020
- Single gene therapy injection surprisingly boosts vision in both eyes - New Atlas - December 17th, 2020
- Freeline takes the haemophilia B gene therapy fight to Uniqure - Vantage - December 17th, 2020
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- Gene Therapy, Absolutely and For Real | In the Pipeline - Science Magazine - December 14th, 2020
- Treatment with Investigational LentiGlobin Gene Therapy for Sickle Cell Disease (bb1111) Results in Complete Elimination of SCD-Related Severe... - December 14th, 2020
- Rocket Pharmaceuticals in orbit after gene therapy read-out - - pharmaphorum - December 14th, 2020
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- ASH 2020: Novel Gene Therapy Found to be Safe and Effective in Treatment of Hemophilia B - OncoZine - December 14th, 2020
- Gene Therapy Unexpectedly Improves Vision In Both Eyes Of Patients Suffering A Form Of Blindness - IFLScience - December 14th, 2020
- Innovative payment models to support cell and gene therapies on the rise - MedCity News - December 14th, 2020
- Better education needed to give patients improved understanding of gene therapies, new review highlights - University of Birmingham - December 14th, 2020
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