Spark Therapeutics (ONCE), a fully integrated gene therapy company dedicated to challenging the inevitability of genetic disease, today announced it has entered into a licensing agreement with Novartis Pharmaceuticals to develop and commercialize investigational voretigene neparvovec outside the U.S., while Spark Therapeutics will continue to exclusively commercialize LUXTURNA(TM) (voretigene neparvovec-ryzl) in the U.S. Under the agreement, Spark Therapeutics will retain regulatory responsibility for obtaining European Medicines Agency approval for investigational voretigene neparvovec. Spark Therapeutics also entered into a separate agreement to manufacture and supply investigational voretigene neparvovec to Novartis. No other programs in Spark Therapeutics` pipeline are part of this agreement.

Under the terms of the licensing agreement, Novartis will pay Spark Therapeutics $105 million in cash as an upfront fee. Spark Therapeutics is eligible to receive up to an additional $65 million in cash milestone payments based on near-term European Regulatory Agency (EMA) regulatory approval and initial sales outside the U.S. in certain markets. Spark Therapeutics is also entitled to receive royalty payments on net sales of investigational voretigene neparvovec outside the U.S.

"By leveraging Novartis` large, existing commercial and medical infrastructure in ophthalmology, as well as its commitment to commercializing genetic-based medicines, we help ensure that more patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy who live outside the U.S., and importantly outside of Europe, have access to investigational voretigene neparvovec," said Dan Faga, chief business officer, Spark Therapeutics. "We intend to use the proceeds from this transaction to continue to develop our robust pipeline of investigational gene therapies to create a path to a world where no life is limited by genetic disease."

Indication and Important Safety Information for LUXTURNA

LUXTURNA(TM) (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 holes, foveal 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 greater than or equal to 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%).

Immunogenicity

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.