LCA patients gain benefit from Spark Therapeutics' gene therapy treatment, Luxturna

(c) Mass Eye & Ear

With the approval of Spark Therapeutics' Luxturna for Leber's Congenital Amaurosis (LCA), eye institutions around the US have started offering the treatment to their patients. In recent days, we have heard of this treatment being offered for the first time after the approval in Massachusetts Eye and Ear in Boston, followed the same day by the Children's Hospital of Los Angeles. A few days later, Bascom Palmer Eye Institute completed its first case.

Massachusetts Eye and Ear, in a way, made medical history by performing the first post-FDA approval gene therapy for patients with a form of inherited blindness. The occasion marks the beginning of a new era in medicine, as it is the first time any FDA-approved gene therapy has been given to a patient for any inherited disease.¹

The treatment, commercially identified as Luxturna, was developed by Spark Therapeutics and approved in December last year by the Food and Drug Administration (FDA) for patients aged 12 months and older.¹

The breakthrough one-time treatment replaces a defective gene called RPE65 located in the retina, the membrane at the back of the eye that detects light and color, with a healthy copy made from artificial DNA, the equivalent of human DNA. RPE65 is responsible for producing a protein that makes light receptors work in the eye.²

Luxturna has been shown to improve visual function in children and adults with inherited retinal disease caused by mutations in the gene RPE65. The inaugural patient was a 13-year-old boy from New Jersey.¹

Synthetic genes are first grown in a lab and then inserted into viruses commonly found in the human eye. The viruses — whose mission is to invade eye cells and infuse genetic material into them — are then carefully placed in the patient's retina.³

The therapy is administered through a surgical procedure and patients are discharged later that same day with an eye patch protecting the treated eye. Approximately one week later, the patient returns to have the procedure performed on their second eye.²

The newly approved treatment involves injecting a modified virus into a patient's eyes to correct a deficiency caused by mutations in the RPE65 gene. These mutations prevent the production or function of a protein needed for proper functioning of the retina, the light-sensitive tissue in the back of the eye that initiates vision. Within 24 hours of the injection, the DNA sequence, enveloped by a benign virus, would wiggle its way through the retina’s light receptor cells and start producing the correct version of the protein.⁴

The treatment affects different patients in different ways. Sometimes the vision improvement is dramatic. One patient in the FDA trial no longer needed to attend a specialized school for children with blindness.3 Following treatment, this therapy helped restore vision in a clinical trial for people between the ages of 4 and 44, with most participants reported recognizing faces, seeing stars and being able to read for the first time in years.¹

Because there were no other meaningful treatments available for this incurable disease, the FDA approved the treatments more rapidly than it typically does, under programs called Breakthrough Therapy and Priority Review. These sorts of accelerated approvals require drug companies and clinicians to continue monitoring the treatments after their initial FDA approval, to ensure they're truly safe and effective enough for consumers to use. The safety warnings on the Luxturna website underscore these potential hazards, including potential eye infections and further declines in vision.³

Although gene therapies provide treatments for historically unmanageable diseases, they can be markedly more expensive than conventional treatments, especially if the disease — such as this retinal mutation — is rare. The price right now is prohibitively high for most Americans: It costs $425,000, per eye.³

Regarding the cost, Thomas Ciulla, MD, MBA, a retinal physician who also works for Spark Therapeutics, writes that "our health care system is poorly equipped to value this type of therapy. Our system willingly pays for chronic medications, but it is less effective in handling reimbursement for therapies that potentially deliver life-long benefits in one dose or one administration. Unlike other therapies developed to treat chronic, rare diseases, which typically capture the value of the treatment over a patient’s lifetime, this proposed gene therapy must capture the value of the benefit it provides coincident with one-time use."⁵

Dr. Ciulla continues that "with the average life expectancy in the United States approaching 80 years, the direct and indirect costs of caring for one blind patient can potentially reach millions of dollars. This cost is compounded by other economic factors that extend well beyond treatment regimens, such as loss of productivity, as reflected in the high unemployment rate among blind American adults."⁵

Dr. Ciulla also adds that "this scenario could begin to change with the adoption of medical breakthroughs such as gene therapy. The costs of developing such innovations are high, and it is more difficult to spread those costs when the affected patient population is relatively small. A company’s ability to continue investing in and developing these potential treatments hinges largely on whether they can find a place in the market."⁵

To circumvent the issues with the high cost, Spark Therapeutics has been working with certain health insurers to share the risk, by willing to pay rebates if patient outcomes fail to meet a specified threshold, thereby linking the payment for the treatment to both short-term efficacy (30-90 days) and longer-term durability (30 months) measures. 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 the treatment.⁶

In addition, 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.¹

In addition, with the higher-value and higher-cost therapies such as Luxturna, the traditional “buy and bill” model followed by health care institutions 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’ 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. 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 the treatment. Under this arrangement, Spark Therapeutics will assume all drug in-transit, storage and handling risks.⁶

Spark Therapeutics is also in discussions with Centers for Medicare & Medicaid Services 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.⁶

With the focus in helping patient navigate the complex scenario of getting the treatment and the costs involved, Spark Therapeutics has established a patient help division 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 the treatment and immediate follow-up care.⁶

Though the patient numbers are small, and the costs of the treatment are high, this being the first gene-therapy treatment of its kind that has gained approval is no small feat. The commercial success of this path-breaking treatment will spur other commercial entities and academic centers to take up research and development in similar and other genetic disorders, most of which are almost a death knell for a patient due to lack of any meaningful availability of treatment.

Sources: 1 2 3 4 5 6

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