Spark Therapeutics Announces First-of-their-kind Programs to Improve Patient Access to LUXTURNA™ (voretigene neparvovec-rzyl), a One-time Gene Therapy Treatment

Company offers outcomes-based rebates and an innovative contracting model that support patient access in the U.S. while aiming to reduce risk and financial burden for payers and treatment centers

Harvard Pilgrim and affiliates of Express Scripts have agreed in principle to participate; discussions underway with additional commercial insurers

Proposal to the Centers for Medicare and Medicaid Services(CMS) would enable Spark Therapeutics to offer payers the option to spread payment over multiple years

PHILADELPHIA, Jan. 03, 2018 (GLOBE NEWSWIRE) — Spark Therapeutics (NASDAQ:ONCE), a fully integrated gene therapy company dedicated to challenging the inevitability of genetic disease, today announced three new payer programs: an outcomes-based rebate arrangement with a long-term durability measure, an innovative contracting model and a proposal to CMS under which payments for LUXTURNA™ (voretigene neparvovec-rzyl) would be made over time. Together, these initiatives aim to help ensure eligible U.S. patients have access to LUXTURNA, a one-time gene therapy indicated for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. LUXTURNA should only be administered to patients who have viable retinal cells as determined by their treating physicians. Spark Therapeutics has reached agreement in principle with Harvard Pilgrim to make LUXTURNA available under the outcomes-based rebate arrangement and the innovative contracting model that aims to reduce risk and financial burden for payers and treatment centers. Spark Therapeutics also has reached an agreement in principle with affiliates of Express Scripts to enable the innovative contracting model.

“To help ensure eligible patients have access to LUXTURNA, we are striving to bring the same level of innovation applied in development to the delivery of, and access to, this product,” said Jeffrey D. Marrazzo, chief executive officer of Spark Therapeutics. “We believe that access to therapy is a shared responsibility among Spark Therapeutics, payers, health benefit providers, physicians and treatment centers. We have been working with stakeholders across the healthcare sector to help ensure that appropriate patients have access to a product that challenges all of the current conventions of how patients are treated, how products are delivered and how payments are handled.”

LUXTURNA and other potential one-time therapies face unique health insurance challenges given current practices and regulations in the U.S. healthcare system. Barriers to offering alternate models include the system’s focus on short-term value, largely because most patients switch health insurance companies on average every three years; government price reporting requirements that are not designed to reflect certain outcomes-based arrangements, therefore limiting a manufacturer’s ability to offer significant performance-based rebates, particularly for diseases with small patient populations; and complicated distribution models, which add costs and financial risk to parties involved in the delivery and reimbursement of specialty drugs and specialized medical care.

“Over these past few months, we have been working with health insurers to create innovative pathways for access to LUXTURNA that may serve as models for other one-time administered gene therapies in the future,” said Marrazzo. “Our work is not done, but we believe that the offerings we are announcing today will help ensure that eligible U.S. patients have the coverage and financial support they need to gain access to both LUXTURNA and the specialized medical care required to deliver the product at treatment centers.”

Outcomes-based rebate arrangement aligns with longer-term efficacy of LUXTURNA
Spark Therapeutics will share risk with certain health insurers by paying rebates if patient outcomes fail to meet a specified threshold, thereby linking the payment for LUXTURNA to both short-term efficacy (30-90 days) and longer-term durability (30 months) measures that are unique to this one-time gene therapy. The short-term and long-term measures will be based on full-field light sensitivity threshold (FST) testing scores, with a baseline to be established for each eligible patient before administration of LUXTURNA.

In addition to its agreement in principle with Harvard Pilgrim, Spark Therapeutics is in active discussions with other commercial insurers regarding this offering.

“Harvard Pilgrim is excited not only about the approval of this innovative and first-of-its-kind gene therapy for genetic disease, but also for the opportunity to work with Spark Therapeutics on an outcomes-based arrangement that will contribute to our goal of not only ensuring access for our members but also the need to maintain affordability on the cost side,” said Michael Sherman, M.D., senior vice president and chief medical officer at Harvard Pilgrim, a leading not-for-profit health services company with flagship health plans in New England, providing coverage to more than 1.2 million members, while more than two million individuals are served through subsidiaries providing integrated care management and health coaching. “This outcomes-based rebate arrangement is truly innovative, as it ties payment for the therapeutic not only to a short-term goal, but also to a longer-term, 30-month assessment of efficacy.”

Innovative contracting model supports patient access while reducing costs to payers, as well as financial burden and risk of traditional “buy and bill” models for treatment centers
Traditionally, specialty medications administered by physicians in hospitals are purchased by the institution where the patient is treated. The institution then bills the payer, typically including a mark-up on the product. With higher-value, higher-cost therapies, this traditional “buy and bill” model may represent a significant financial burden and risk to the institution, and creates the potential for substantial additional costs to the payer.

Under Spark Therapeutics’ innovative contracting model, the company would enter into an agreement with commercial payers under which the payer or payer’s specialty pharmacy, rather than the treatment center, purchases LUXTURNA. As a part of this agreement, the payer agrees to provide coverage for its members consistent with U.S. Food and Drug Administration (FDA) labeling of LUXTURNA, expedite benefits processing and cap patient out-of-pocket amounts at in-network limits. Separately, the payer would independently agree with the treatment center on reimbursement that is commensurate with the type of specialized medical care required to deliver LUXTURNA. Under this arrangement, Spark Therapeutics will assume all drug in-transit, storage and handling risks.

Spark Therapeutics is working with affiliates of Express Scripts to enable this innovative contracting model by leveraging their specialty distribution and specialty pharmacy capabilities.

“Our Express Scripts affiliates, CuraScript Specialty Distribution and Accredo Specialty Pharmacy, look forward to working with Spark Therapeutics on its innovative contracting model to ensure this life-changing therapy is available to eligible patients,” said Steve Miller, M.D., senior vice president and chief medical officer of Express Scripts, a leading pharmacy benefits provider serving patients across the U.S. “This is the first of what we expect to be many transformative gene therapies coming to market, with the potential to provide life-changing health benefits to patients we serve. For one-time therapies like LUXTURNA, we believe non-traditional payment and distribution models are needed to ensure that the needs of patients, payers and providers are fully represented and result in a balanced solution for all parties.”

Spark Therapeutics is in active discussions with other national and regional payers regarding this innovative contracting model for LUXTURNA, which could serve as a model for other one-time therapies.

Spark Therapeutics is in discussions with CMS on a proposal that would enable the company to offer payers the option to spread payment over multiple years, while providing flexibility for greater outcomes-based rebates
Based on feedback from payers, Spark Therapeutics has been seeking solutions that would allow customers to pay for LUXTURNA in installments over several years rather than in a single, up-front payment. Due to current government price reporting requirements, it is not feasible for Spark Therapeutics to offer installment payments, or to offer outcomes-based rebates above a certain threshold. Spark Therapeutics has submitted a proposal to CMS to conduct a demonstration project for LUXTURNA that would enable Spark Therapeutics to offer commercial and government payers an installment payment option, as well as greater rebates tied to clinical outcomes.

“We are committed to finding a novel solution to providing an installment payment option to payers that ensures access for patients while helping to address the budgetary challenges of one-time payments for a long-term outcome.We are encouraged by CMS’ willingness to engage with us in exploring a new model,” said Marrazzo. “We are also eager to work with CMS to enable more meaningful rebates as part of the pay-for-performance model. We are confident in the clinical meaningfulness of LUXTURNA and willing to stand behind the product’s efficacy and durability from a single dose.”

Separately, Spark Therapeutics has been actively involved in policy discussions that explore new policy initiatives for one-time therapies led by groups like the Duke-Margolis Center for Health Policy’s Value-Based Payment Consortium.

“Spark Therapeutics’ effort to implement new pricing approaches with both public and private payers is a critical step to put the focus on long-term outcomes, not just more treatments,” said Mark McClellan, M.D., Ph.D., Robert J. Margolis professor of business, medicine and policy and director of the Duke-Margolis Center for Health Policy at Duke University, former FDA commissioner and a former CMS administrator. “We are pleased to be working with manufacturers like Spark Therapeutics, along with patient groups, clinicians, employers and public officials, who are willing to explore and implement innovative access arrangements that can derive greater value from breakthrough therapies.”

If discussions with CMS do not result in Spark Therapeutics being able to offer an installment option, Spark Therapeutics has developed an approach that would permit its distributor to independently make alternative payment options available to payers, which may include an installment or financing option.

Patient assistance programs for accessing LUXTURNA to include financial support for patients and their caregiver to travel to treatment centers
Spark Therapeutics is committed to help ensure that appropriate patients in the U.S. with a confirmed genetic diagnosis of biallelic RPE65 mutation-associated retinal dystrophy and viable retinal cells have access to LUXTURNA. The company has established Spark Therapeutics Generation Patient ServicesSM to support commercially insured patients and their caregivers in the U.S. through the treatment experience. The team at Spark Therapeutics Generation Patient Services will assist eligible and enrolled commercially insured patients in navigating the insurance process, and will provide options to support their travel and accommodation logistics and costs to and from treatment centers, as well as assistance with other out-of-pocket costs related to the treatment. For a commercially insured patient who seeks treatment in-network, this means there should be zero cost to the patient for LUXTURNA and immediate follow-up care.

More information is available for patients, caregivers and healthcare professionals in the U.S. at or by calling 1-833-SPARK-PS (833-772-7577).

Indication and Important Safety Information for LUXTURNA
LUXTURNA (voretigene neparvovec-rzyl) is an adeno-associated virus vector-based gene therapy indicated for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy.

Patients must have viable retinal cells as determined by the treating physicians.

Warnings and Precautions

  • Endophthalmitis may occur following any intraocular surgical procedure or injection. Use proper aseptic injection technique when administering LUXTURNA, and monitor for and advise patients to report any signs or symptoms of infection or inflammation to permit early treatment of any infection.
  • Permanent decline in visual acuity may occur following subretinal injection of LUXTURNA. Monitor patients for visual disturbances.
  • Retinal abnormalities may occur during or following the subretinal injection of LUXTURNA, including macular holesfoveal thinning, loss of foveal function, foveal dehiscence, and retinal hemorrhage. Monitor and manage these retinal abnormalities appropriately. Do not administer LUXTURNA in the immediate vicinity of the fovea. Retinal abnormalities may occur during or following vitrectomy, including retinal tears, epiretinal membrane, or retinal detachment. Monitor patients during and following the injection to permit early treatment of these retinal abnormalities. Advise patients to report any signs or symptoms of retinal tears and/or detachment without delay.
  • Increased intraocular pressure may occur after subretinal injection of LUXTURNA. Monitor and manage intraocular pressure appropriately.
  • Expansion of intraocular air bubbles Instruct patients to avoid air travel, travel to high elevations or scuba diving until the air bubble formed following administration of LUXTURNA has completely dissipated from the eye. It may take one week or more following injection for the air bubble to dissipate. A change in altitude while the air bubble is still present can result in irreversible vision loss. Verify the dissipation of the air bubble through ophthalmic examination.
  • Cataract Subretinal injection of LUXTURNA, especially vitrectomy surgery, is associated with an increased incidence of cataract development and/or progression.

Adverse Reactions

  • In clinical studies, ocular adverse reactions occurred in 66% of study participants (57% of injected eyes), and may have been related to LUXTURNA, the subretinal injection procedure, the concomitant use of corticosteroids, or a combination of these procedures and products.
  • The most common adverse reactions (incidence ≥ 5% of study participants) were conjunctival hyperemia (22%), cataract (20%), increased intraocular pressure (15%), retinal tear (10%), dellen (thinning of the corneal stroma) (7%), macular hole (7%), subretinal deposits (7%), eye inflammation (5%), eye irritation (5%), eye pain (5%), and maculopathy (wrinkling on the surface of the macula) (5%).

Immune reactions and extra-ocular exposure to LUXTURNA in clinical studies were mild. No clinically significant cytotoxic T-cell response to either AAV2 or RPE65 has been observed. Study participants received systemic corticosteroids before and after subretinal injection of LUXTURNA to each eye, which may have decreased the potential immune reaction to either AAV2 or RPE65.

Pediatric Use
Treatment with LUXTURNA is not recommended for patients younger than 12 months of age, because the retinal cells are still undergoing cell proliferation, and LUXTURNA would potentially be diluted or lost during the cell proliferation. The safety and efficacy of LUXTURNA have been established in pediatric patients. There were no significant differences in safety between the different age subgroups.

Please see the full U.S. Prescribing Information for LUXTURNA here.

Clinical Trial Overview of LUXTURNA™ (voretigene neparvovec-rzyl)
The safety and efficacy of LUXTURNA were assessed in one open-label, dose-exploration Phase 1 safety study (n=12) and one open-label, randomized, controlled Phase 3 efficacy and safety study (n=31) in pediatric and adult participants (range 4 to 44 years) with biallelic RPE65 mutation-associated retinal dystrophy and sufficient viable retinal cells.

Of the 31 participants enrolled in the Phase 3 study, 21 were randomized to receive subretinal injection of LUXTURNA and 10 were randomized to the control (non-intervention) group. One participant in the intervention group discontinued from the study prior to treatment and one participant in the control group withdrew consent and was discontinued from the study. All nine participants randomized to the control group elected to crossover and receive LUXTURNA after one year of observation. All participants in these studies continue to be followed for long-term safety and efficacy. LUXTURNA Phase 3 clinical trial data, including data from the intervention group of all randomized participants through the one-year time point has been previously reported in (The Lancet).

The efficacy of LUXTURNA in the Phase 3 study was established based on the multi-luminance mobility test (MLMT) score change from baseline to one year. MLMT was designed to measure changes in functional vision as assessed by the ability of a participant to navigate a course accurately and at a reasonable pace at seven different levels of illumination, ranging from 400 lux (corresponding to a brightly lit office) to one lux (corresponding to a moonless summer night). Each light level was assigned a score ranging from zero to six, with a higher score indicating that a participant could pass MLMT at a lower light level. A score of negative one was assigned to participants who could not pass MLMT at a light level of 400 lux. MLMT score change was defined as the difference between the score at baseline and the score at one year with a positive score change indicating that a participant was able to complete MLMT at a lower light level. Additional clinical outcomes included white light full-field light sensitivity threshold (FST) testing and visual acuity.

LUXTURNA Phase 3 clinical study results showed a statistically significant difference between the intervention group (n=21) and control participants (n=10) at one year in median bilateral MLMT score change (intervention minus control group difference of 2; p=0.001) and median first-treated eye MLMT score change (intervention minus control group difference of 2; p=0.003). After crossing over to receive LUXTURNA, participants in the control group showed a similar response to those in the intervention group. The median bilateral MLMT score change of two was observed for the intervention group at the 30-day timepoint. This change score has been sustained for at least three years for the original intervention group and at least two years in the crossover group in the Phase 3 clinical study. In addition, participants who received LUXTURNA showed a statistically significant improvement from baseline to one year in white light FST in the intervention group compared to the control group. The change in visual acuity from baseline to one year was not significantly different between the intervention and control participants.

The U.S. Prescribing Information for LUXTURNA includes the following Warnings and Precautions: endophthalmitis; permanent decline in visual acuity; retinal abnormalities; increased intraocular pressure; expansion of intraocular air bubbles; and cataract. The most common adverse reactions (incidence ≥ 5%) were conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear, dellen (thinning of the corneal stroma), macular hole, subretinal deposits, eye inflammation, eye irritation, eye pain and maculopathy (wrinkling on the surface of the macula).

About RPE65 Mutation-associated Inherited Retinal Disease (IRD)
Inherited retinal diseases (also known as inherited retinal dystrophies) are a group of rare blinding conditions caused by one of more than 220 different genes, often disproportionally affecting children and young adults. Based on Spark Therapeutics’ assessment of available epidemiology data, we believe the prevalent population in the U.S., Europe and select additional markets in the Americas and Asia/Pacific is up to approximately 6,000 individuals, in total, with biallelic RPE65 mutations. We estimate that between 1,000-2,000 people in the U.S. have vision loss due to these biallelic RPE65 mutations. In addition, we estimate an expected 10-20 new patients a year are born with RPE65 mutations in the U.S. Not all patients with confirmed RPE65 mutations will be appropriate candidates for LUXTURNA.

People living with IRD due to biallelic RPE65 mutations nearly all progress to complete blindness. They often experience night blindness (nyctalopia) due to decreased light sensitivity in childhood or early adulthood and involuntary back-and-forth eye movements (nystagmus). As the disease progresses, individuals may experience loss in their peripheral vision, developing tunnel vision, and eventually, they may lose their central vision as well, resulting in total blindness. Independent navigation becomes severely limited, and vision-dependent activities of daily living are impaired. There are currently no approved pharmacologic treatment options for IRD due to biallelic RPE65 mutations.

About Gene Therapy
Gene therapy is an approach to treat or prevent genetic disease by seeking to augment, replace or suppress one or more mutated genes with functional copies. It addresses the root cause of an inherited disease by enabling the body to produce a protein or proteins necessary to restore health or to stop making a harmful protein or proteins, with the potential of bringing back function in the diseased cells and/or slowing disease progression. To deliver the functional gene into the cell, a vector is used to transport the desired gene and is delivered either intravenously or injected into specific tissue. The goal is to enable, through the one-time administration of gene therapy, a lasting therapeutic effect.

About Spark Therapeutics
At Spark Therapeutics, a fully integrated company committed to discovering, developing and delivering gene therapies, we challenge the inevitability of genetic diseases, including blindness, hemophilia and neurodegenerative diseases. We have successfully applied our technology in the first FDA-approved gene therapy in the U.S. for a genetic disease, and currently have three programs in clinical trials, including product candidates that have shown promising early results in patients with hemophilia. At Spark, we see the path to a world where no life is limited by genetic disease. For more information, visit, and follow us on Twitter and LinkedIn.

Cautionary note on forward-looking statements
This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the company’s product LUXTURNA™ (voretigene neparvovec-rzyl). The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘predict,’’ ‘‘will,’’ ‘‘would,’’ ‘‘could,’’ ‘‘should,’’ ‘‘continue’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that: (i) we do not enter into agreements with Harvard Pilgrim, affiliates of Express Scripts or other commercial insurers to make LUXTURNA available for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy; (ii) payers, health benefit providers, physicians and hospitals do not believe access to therapy is a shared responsibility; (iii) our payer and patient offerings will not ensure eligible patients have the coverage and financial support they need to gain access to LUXTURNA and the required specialized medical care; (iv) payers terminate any agreements they enter into with us; (v) our proposal to the Centers for Medicare & Medicaid Services (CMS) is not accepted; (vi) in the event our proposal to CMS does result in our ability to offer an installment option, payers do not accept alternative payment options from our distributor; (vii) the improvements in functional vision demonstrated by LUXTURNA in our clinical trials may not be sustained over extended periods of time; and (vii) any one or more of our product candidates in preclinical or clinical development will not successfully be developed and commercialized. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties and other important factors, in our Annual Report on Form 10-K, our Quarterly Reports on Form 10-Q and other filings we make with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Spark undertakes no duty to update this information unless required by law.

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