First FDA-approved gene-therapy procedure for inherited blindness performed in US. Advance is fantastic news, but same quandary: Who can afford it?

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The News:

Massachusetts Eye and Ear, a Harvard teaching hospital based in Boston, recently became the first institution to treat a patient’s inherited retinal disorder with gene therapy.

The patient, a 13-year-old boy named Jack Hogan, was born with a defective version of the RPE65 gene, a mutation affecting 1,000-2,000 Americans that prevents the proper production of a protein that lets the eyes process light. For Jack, this meant struggles in the classroom, and poor night vision that precluded sports with outdoor games that swung into evening hours.

A drug called Luxturna (voretigene neparvovec-rzyl), developed by Spark Therapeutics Inc. (Philadelphia) and approved by the FDA in December, could change all of that, according to a press release.

Unlike other gene therapies already in use, Luxturna works by delivering a healthy, lab-grown copy of the defective gene into patients, rather than genetically modifying patients’ own cells–making it the first genuine gene therapy approved by the FDA.

Though it will take time to comprehend the full therapeutic benefit for Jack, there is reason to believe his sight will improve; in clinical trials, Luxturna improved most patients’ vision either moderately or significantly. Post-approval success as it is administered across the country will invigorate hope for the role of gene therapies in treating patients with a wide range of conditions involving genetic variations.

Luxturna was approved in December for patients 12 months of age and older. Clinical trials demonstrated the improvement in visual function in children and adults with inherited retinal disease caused by mutations in the gene RPE65. The safety and efficacy of Luxturna were established in a clinical development program with 41 patients between ages 444 that had confirmed biallelic RPE65 mutations.

The primary evidence was based on a Phase 3 study with 31 participants that measured the change from baseline to 1 year in a patient’s ability to navigate an obstacle course at various light levels. Patients that received Luxturna demonstrated significant improvements in the ability to complete the obstacle course at low light levels versus the control group. The most common adverse effects included conjunctival hyperemia (excess blood), cataract, increased intraocular pressure and retinal tear.

Following the approval, FDA commissioner Scott Gottlieb, MD, said he believed gene therapies like Luxturna, “…will soon be mainstays in treating, and maybe curing, many of our most devastating and intractable illnesses.”

Massachusetts Eye and Ear is one of only eight medical centers in the US certified to perform the gene therapy.

Steve’s Take:

While trial evidence demonstrated the success that the Spark Therapeutics’ novel gene therapy Luxturna holds for patients, but as I’ve pointed out before the therapy’s cost immediately came into question. On January 3, 2018 Spark priced its potential blindness cure at an eye-popping $850,000 for both eyes (in one procedure) or $425,000 per single eye.

Egads. And I though checkpoint inhibitors, CAR T-cell therapy and CRISPR-Cas9 were expensive.

Sure. This would be life-changing, to put it mildly, for blind patients.

But, “Promoting the potential cure for a form of blindness, while also making it inaccessible to most patients by cost is repugnant,” Michael Steck, OD, said in MD Magazine. “These therapies may very well cure diseases, but the means to get it will kill the patient.”

Dr. Steck’s statement about the cost of Luxturna killing the patient may be just a bit over the top, but why is the price for this blindness treatment so high? It’s because gene therapy is particularly suited to blindness and other eye diseases, explains.

First, and simply put, the eye is an immune-privileged area of the body where the immune system cannot detect and react against the viral DNA used as a delivery vector. Second, the cells of the retina that detect light do not get renewed as we age.

“These cells don’t renew or mutate, and therefore should conserve expressions all their lifetime,” says Bernard Gilly, CEO of GenSight Biologics SA (Paris). “A study on neurons in monkeys showed up to eight years of expression of the protein.”

Although GenSight’s gene therapy did improve the sight of the patients significantly in one of their eyes, recent Phase 3 results showed that so did the placebo injected into the other eye. The company is now trying to figure out whether the therapy is affecting both eyes or it just is no better than a placebo.

Nightstar Therapeutics PLC from London is getting closer to launching a gene therapy for choroideremia, another rare disorder that causes blindness. The company has just started a Phase 3 trial testing a gene therapy aiming to replace a missing protein necessary to remove waste from retinal cells to keep them healthy.

Paris-based Horama SAS is seeking to cure retinitis pigmentosa, a hereditary disease that results in progressive vision loss. The company has just started a first trial in humans with a gene therapy that targets one of the condition’s most common mutations

And another Parisian biotech called Eyevensys SAS is seeking to remove the use of viruses in gene therapy for the eye. The company uses an electrical field to increase the permeability of the cell membrane and injects the DNA directly into the ciliary muscle–a tiny muscle that surrounds the iris and adjusts the focus.

Bottom Line:

Is gene therapy for everybody?

The progress made by more traditional gene-therapy approaches is astounding, Labiotech notes, but one of the limitations of gene therapy is that each treatment can only fix a single gene. That significantly reduces the number of people that can benefit from a gene therapy when considering diseases like retinitis pigmentosa, which can be caused by mutations in 60 different genes.

Developing a gene therapy is extremely expensive, so developing 60 doesn’t seem feasible considering many of these mutations can be extremely rare. So instead, some companies are designing new approaches to make a single therapy suitable for everyone.

All this news surrounding Spark, Nightstar and others sounds super great, but the jaw-dropping cost of Luxturna, for example, elevates it to the most expensive drug in the world. And you can bet payers and insurers won’t reimburse for a treatment where they ultimately lose money, no matter how mind boggling and life altering the result is for the patient. It’s an entirely different cost-benefit calculation with cancer treatments, though. A cure in that space can save the payer/insurer potentially millions.

One of the solutions some companies are testing include spacing out the payment over time and conditioning the payment to the therapy working. For example, Spark Therapeutics has set up a payment scheme for Luxturna in the US that is based on the outcome of the gene therapy. The company will offer partial refunds depending on whether the therapy works in the short term (30-90 days) or the long term (30 months).

Steve's Take: These expensive #gene therapies, like #Luxturna, should be covered by #healthinsurance Click To Tweet

The FDA-approved gene therapies are designed to be one-time cures, and for many patients they’ve been just that, FiercePharma notes. Many more gene therapies are moving through biopharma pipelines. And that presents a challenge to the industry, which of course relies on the cash and profits their products generate over time, said Goldman Sachs analyst Salveen Richter in a note to investors.

Cancer poses less of a business-model conundrum than many of the other diseases pursued by gene therapy developers, Richter suggested, because the “incident pool remains stable,” posing “less risk to the sustainability of a franchise.” That portends more M&A activity to come in oncology, he said.

Gene-therapy companies got a boost last month after Novartis AG’s $8.7 billion deal to buy AveXis, making good on CEO Vasant Narasimhan’s promise to strike deals to refocus the company. AveXis has several ongoing clinical studies for the treatment of SMA, an inherited neurodegenerative disease caused by a defect in a single gene, the survival motor neuron (SMN1). Novartis paid $218 per share–a hefty 88% premium to the closing price of shares prior to the deal’s announcement.

Analysts at Chardan Capital Markets say companies like Spark Therapeutics and Nightstar could be among the Swiss titan’s next targets. Spark shares gave gained 8% to $76.02 since the AveXix deal while Nightstar has risen 7% to $13.99.

Of the latter, I like Spark Therapeutics as the most likely M&A target. And of the 21 analysts who follow the company, the mean consensus is that shares will outperform the market, with a high 12-month target price of $103. That’s a 46% spread from its current closing price.

Steve Walker has no position in any stocks mentioned. MedContent Inc. has no position in any stocks mentioned. has a disclosure policy.

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