Preliminary Phase 1/2 data for investigational SPK-8011 for hemophilia A show dramatic reductions in bleeds and infusions for first 12 participants with an encouraging safety profile, as of Nov. 2, 2018, data cutoff

All five participants in the first two dose cohorts, the longest of whom is out 78 weeks post SPK-8011 infusion, have shown persistent, stable factor VIII activity levels in this ongoing study

Planning to initiate a Phase 3 run-in study by the end of 2018

PHILADELPHIA, Dec. 02, 2018 (GLOBE NEWSWIRE) — Spark Therapeutics (NASDAQ: ONCE), a fully integrated, commercial gene therapy company dedicated to challenging the inevitability of genetic disease, today announced updated preliminary data on the first 12 participants in the ongoing Phase 1/2 clinical trial of investigational SPK-8011 in hemophilia A. These data were presented at the 60^th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego by Principal Investigator Lindsey A. George, M.D., assistant professor of pediatrics, The Perelman School of Medicine, University of Pennsylvania and attending physician in the Division of Hematology at Children’s Hospital of Philadelphia.

The 12 participants in the Phase 1/2 trial received a single administration of investigational SPK-8011, including two at a dose of 5×10¹¹ vector genomes (vg)/kg body weight, three at a dose of 1×10¹² vg/kg and seven at a dose of 2×10¹² vg/kg. As of the Nov 2, 2018, data cutoff, no inhibitors, no thrombotic events and no persistent or unresolved transaminase elevations have been observed across a cumulative 9.7 years of data follow-up. Across all three doses, beginning four weeks after vector infusion, there has been a 94-percent reduction in bleeds and a 95-percent reduction in FVIII infusions.

Participants in the 5×10¹¹ vg/kg and 1×10¹² vg/kg dose cohorts have shown dramatic reductions in bleeds and infusions as well as stable FVIII activity with up to 78 weeks of follow-up, with observation ongoing.

Among the five participants treated in the 2×10¹² vg/kg cohort who did not experience an immune response-associated decline in FVIII expression, beginning four weeks after vector infusion, there has been a 100-percent reduction in bleeds and a greater than 99-percent reduction in FVIII infusions, with up to 46 weeks of follow-up.

“These updated data continue to demonstrate impressive reductions in bleeds and infusions across all doses studied, including complete-elimination of bleeds in the five participants at 2×10¹² vg/kg cohort who did not experience a deleterious immune response,” said Katherine A. High, M.D., president and head of research and development at Spark Therapeutics. “Moreover, the safety profile has been excellent, with no inhibitors, no prolonged transaminase elevations and no thromboembolic events for the 12 participants. Consistent with our expectations and aligned with prior results using Spark Therapeutics’ adeno-associated viral (AAV) technology platform, the participants in the first two dose cohorts have seen durable responses characterized by stable factor VIII activity levels out as long as one and a half years.”

Seven of the 12 participants received a tapering course of reactively administered oral steroids, including five in the 2×10¹² vg/kg cohort, in response to an alanine aminotransferase (ALT) elevation above the patient’s baseline, declining FVIII levels and/or positive IFN-g enzyme-linked immunospots (ELISPOTs). For all participants, steroids led to rapid normalization of ALT and/or ELISPOTs.

All participants responded to vector infusion with an increase in circulating levels of FVIII. As previously disclosed, two participants in the 2×10¹² vg/kg cohort had a suspected capsid immune response that caused their FVIII levels to decline to less than 5 percent. One of these participants did not rapidly respond to reactively administered oral steroids and was electively admitted to the hospital to receive two intravenous (IV) methylprednisolone infusions. The event subsequently resolved without sustained deleterious effects other than the decrease in FVIII activity. The admission to hospital for these infusions met the criteria for a serious adverse event (SAE).

Across the study through the data cutoff, the 12 participants demonstrated rapid clearance of vector from body fluids, with median time to clear vector DNA from saliva, semen and urine of two weeks.

“We expect to provide a further update of the Phase 1/2 study in mid-2019, which will include an additional 2×10¹² vg/kg dose cohort of five to 10 participants dosed with material from our suspension manufacturing process and will also evaluate a prophylactic – rather than reactive – approach to steroid administration with the goal of reducing or eliminating immune responses,” added High.

Spark Therapeutics intends to initiate a Phase 3 run-in study by the end of 2018 to collect prospective observational data on trial participants.

Please see Dr. George’s presentation here.

About SPK-8011 for hemophilia A
Investigational SPK-8011, a novel bio-engineered adeno-associated viral (AAV) vector utilizing the AAV-LK03 capsid, also referred to as Spark200, contains a codon-optimized human factor VIII gene under the control of a liver-specific promoter. The Food and Drug Administration (FDA) granted orphan-disease designation and breakthrough therapy designation in the U.S., while the European Commission has granted orphan designation to SPK-8011.

About Spark Therapeutics’ hemophilia portfolio
Our goal is to create a world where no life is limited by hemophilia, where we eliminate bleeding and free patients from the need for regular treatment. Fidanacogene elaparvovec (formerly SPK-9001) for hemophilia B is now in a Phase 3 clinical trial being conducted by Pfizer, Inc. SPK-8011 for hemophilia A is the second investigational hemophilia gene therapy to emerge from Spark Therapeutics’ leading gene therapy platform. Additionally, the company has received FDA clearance of Investigational New Drug (IND) application for SPK-8016, a novel, internally developed AAV gene therapy candidate aimed at addressing the hemophilia A inhibitor market. Spark Therapeutics retains global commercialization rights to SPK-8011 and SPK-8016.

About Hemophilia A
Hemophilia is a rare genetic bleeding disorder that causes the blood to take a long time to clot because of a deficiency in one of several blood clotting factors. People living with hemophilia are at risk of excessive and recurrent bleeding spontaneously and from modest injuries, which have the potential to be life threatening. There are approximately 15,000 people with hemophilia A in the U.S. and 19,000 in the five major European countries. Hemophilia A is about four times as common as hemophilia B. Hemophilia A is characterized by mutations in the factor VIII gene (F8), which lead to deficient blood coagulation and an increased risk of bleeding or hemorrhaging. The current standard of care for hemophilia A requires recurrent intravenous infusions of either plasma-derived or recombinant factor VIII to control and prevent bleeding episodes. There exists a significant need for novel therapeutics to treat people living with hemophilia.

About Spark Therapeutics
At Spark Therapeutics, a fully integrated, commercial company committed to discovering, developing and delivering gene therapies, we challenge the inevitability of genetic diseases, including blindness, hemophilia, lysosomal storage disorders and neurodegenerative diseases. We have successfully applied our technology in the first gene therapy for a genetic disease approved in the U.S. and EU 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 www.sparktx.com, 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 SPK-FIX program. 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) our early preliminary clinical results for our product candidate, SPK-8011, for hemophilia A, may not be sustained; (ii) our implementation of a prophylactic approach to steroid administration for subjects participating in our SPK-8011 clinical trials may not prevent an immune response; and (iii) we may not be successful in initiating a Phase 3 clinical trial for SPK-8011 and the timing and design of such trial may vary from our expectations. 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.