Luxturna: A Vision for Curative Therapy Access

Veeva’s Matt Wallach in conversation with Jeffrey Marrazzo, CEO of Spark Therapeutics

Matt Wallach (left) and Jeffrey Marrazzo on stage at the Veeva 2019 Commercial & Medical Summit in May.

In December 2017, Spark Therapeutics became the first company ever to have a gene therapy approved in the US. Luxturna, its one-time treatment for adults and children with inherited retinal dystrophy caused by RPE65 gene mutations (a rare genetic disorder which causes vision loss and usually leads to blindness) has since received approval in Europe. 

Spark was founded in March 2013 as a spin-off from Children’s Hospital of Philadelphia (CHOP) to advance and commercialize CHOP’s decades-long research into treating blindness. In February this year, drug giant Roche announced it would be acquiring the gene therapy company for $4.8 billion, a deal that Spark CEO Jeffrey D. Marrazzo said would help “accelerate the development of more gene therapies for more patients with more diseases and further expedite our vision of a world where no life is limited by genetic disease.” 

At this year’s Veeva 2019 Commercial & Medical Summit in Philadelphia, Veeva Co-founder and President Matt Wallach introduced Marrazzo as someone who “basically knows more about commercializing a personalized medicine than anyone on the planet.” Their subsequent fireside chat chronicled Luxturna’s journey so far, from the initial controversies around pricing to its role as a milestone in the ongoing advancement of gene therapy. Here, Pharm Exec presents highlights from that conversation.

MATT WALLACH: Let’s talk through the different innovations associated with Luxturna and how they happened in practice. If we start with pricing, the drug is $850,000, or $425,000 per eye-and that tends to be the headline. Can you talk about how you came up with the price?

JEFF MARRAZZO: One of the first things to clarify is that Luxturna is a one-time price. We already today have five years of follow-up data in patients in the Phase III study who received a single dose and are still benefiting at the same level as they were before. We have patients even in the Phase II study who either self-reported or their physicians have reported that they’re [benefiting after] more than a decade. So, there is data

Luxturna is a single-use treatment for patients with inherited retinal dystrophy caused by the RPE65 gene mutation.

that supports the idea that a one-time treatment can have a long-term, durable effect. What we were trying to do was to think about how, under the current healthcare system, do you take all of the future benefit that you are hopefully going to deliver to a patient, potentially for the rest of their life, and bring that back to a single charge.

Now, that is not the way I think we should be paid. Ultimately, we should be paid on a recurring basis subject to continued performance of the therapy. We should be standing behind these types of products if we believe in them, which we do, but our system is not yet set up to do that. That was one of three different things we did at the beginning. We announced not just the price, but [also] that we were willing to offer partial rebates back [if] the drug didn’t work initially or if it didn’t show sustained effect at around 36 months.

Second, we offered two different ways in which this type of therapy, which is administered by providers, could come to market. One is the traditional way that we all know as “buy and bill.” The second way is to offer a direct model where we would structure a relationship directly with the payer and ultimately not require the hospital to take possession of the therapy and the financial obligation of that, but also for the payer to avoid what has become a practice of marking up those types of provider-administered drugs. On a $425,000/vial product, that can be a substantial amount. Ten percent, 20% is going to be a lot of money. 

The third pricing innovation [is that] we proposed to the Centers for Medicare and Medicaid Services (CMS) a way that we would actually get paid over time, subject to continued performance. This proposal is still in front of the federal government; they are considering that change in policy.

MW: How many of the times that the drug has been administered did it go through the traditional model, and how many times did you eliminate the middle man and go direct to the payer? 

JM: Last year in the market it was roughly about 65, and 35 times we used the direct model and not the traditional model-a little more than half. I think that tells you a little bit about where payers, and to some extent hospitals, are perhaps looking to where the future might land in terms of the way these types of provider-administered drugs would be reimbursed.

MW: How about what the patients have actually been paying when it’s covered? Is it fully covered? Is there a huge copay? 

JM: One of the great successes is the fact that we came out with a number of novel ideas. We wanted to see if we could test the way the system operates with a number of these models, all with an eye toward ensuring access for patients. The thing that has been most gratifying to me is the fact that to date, as far as I’m aware,

there is still no patient that does not either have insurance coverage or a path to insurance coverage.

Importantly, through at least the balance at the end of last year, we had patient assistance programs that were being implemented to cover all the out-of-pocket costs for the patient under the commercial market. That means that a patient, a family doesn’t have to choose between their pocketbook and their child’s vision or their own vision. And that, ultimately, is what we were trying to accomplish.

MW: So, despite what is reported in the headlines-“$850,000!”-the patients and their families actually didn’t pay anything. They had insurance. You have a rebate offer out there-have you had to pay any kind of a rebate?

JM: We’ve had three patients that have gone through this outcomes-based rebate structure. As far as I’m aware, we have not paid any rebates, which again, is consistent with the data that we’ve seen in the Phase III study. We would expect that. You don’t know until you get actually into the real world, but we’ve been extremely pleased by that.

MW: There are patients all over the country. There are eye surgeons all over the country-around 1,800. How did you cover the nation?

JM: We’ve had to establish and build a rather complex supply chain because we need to get a medicine that is required on a chronic recurring basis to patients at the right time and the right place and in the right conditions, e.g., frozen. If you can bring the patient to the therapy, as opposed to bringing the therapy to the patient, it works. Ultimately, we selected 10 treatment centers around the US and now have contracts and established relationships with them. All 10 of them have been operational and treated somebody within the first 12 months. What we’re able to do in that instance is bring together highly specialized individuals who know how to diagnose and treat these patients that require a surgical procedure to deliver Luxturna. It’s also an important part of ensuring the highest quality care. Now it’s possible because we bring the patient to the therapy.

MW: Can you tell us about the people in the field supporting the medication?

JM: We don’t have sales reps. We looked at the question that was in front of us and said, okay, what are the critical things that we need to be able to accomplish in order to make sure that this medicine makes its way to patients? Certainly, access was critical. We have a team that focuses on both the commercial and the government side of the payer space. We also have a team of people that support the education of the medical community. Keep in mind, this wasn’t just the first approved gene therapy-it was the first pharmacologic agent ever approved for any inherited retinal disease (IRD). So, we had a whole community of physicians that did not have much experience with this pharmaceutical product.

However, we did have a large number of those that were dealing with products related to macular degeneration. The medical education was a huge piece of it. And we have a team that does that both internally as well as in the field. But we go beyond this to focus on driving the diagnosis. We have a team of what we call “genetic diagnostic liaisons,” who really work to try to help physicians get access to simple, free genetic tests that can help diagnose.

MW: Because Spark pays for it?

JM: Correct. We thought that was really important because we heard very loud and clear from the patient community that prior to the approval of Luxturna, and even post, there was no pharmacologic treatment for any inherited retinal disease. And there’s more than 200 different genetic subtypes of it.

So, the insurance wasn’t covering even the diagnostic information that patients were yearning for. It wasn’t simple to get, it was complex to try to understand. We’ve put systems in place to cover that for patients. We have a team that focuses on that and then there’s a team that interacts with each of those 10 treatment centers. It all comes together in a very highly collaborative model where all of those pieces and parts of the organization have to work together in service of that individual patient and his or her family.

MW: You had a certain set of expectations and the team worked for years to come up with all of these innovations. What were some of the things that stuck out and that you were not expecting?

JM: On the positive side, I was extremely pleased with the speed in which we got coverage. I can’t tell you the number of conversations I had with many different stakeholders, not least those on Wall Street, who said, “This is not going to be easy. You’re not going to get access. You’re not going to get covered. Insurance is going to push back on it.” I think the speed was one of the biggest upsides and most pleasant surprises, how quickly we got up to now 85% commercial insurance coverage within just a couple of quarters. 

On the other side, I would love to see the types of policy changes we want to make happen more quickly. There are good reasons why the government is taking its time and thinking it through. But these are the types of reforms that need to happen, where we can get paid over time and we can put more than a partial rebate at stake and stand more behind our product. I think that’s ultimately the best way for these therapies to make their way to market.

MW: You said there were 200 different genetically-caused issues or mutations that trigger some form of blindness. What have you found about the number of patients? How big was the market when you started? 

JM: Based on the epidemiologic research that had been done before we launched, we would project up to around 6,000 patients around the globe that might have these types of mutations, with 1,000 to 2,000 of those in the US. But we knew going in that while that is what the epidemiologic data projected, it certainly wasn’t the number of patients that had a confirmed genetic diagnosis. Comparatively, other countries do more in terms of coverage of genetic testing.

MW: There’s no reason for someone to get a genetic test for blindness if there’s no treatment.

JM: Right. That’s certainly the rationale that a payer would look at it and say, “We’re not going to spend hundreds of thousands of dollars on that.” We thought a very small percentage of those patients actually had a genetic test, which is why we put so much effort, even pre-approval in the appropriate way, trying to gather more information about the genetic subtypes of patients with IRDs to inform all of our research and development efforts. Also now, post-approval, we have a specific test targeting people who have RPE65 mutation.

We’re really only four quarters in (as of May) and we’re still finding new patients that didn’t know they had a particular mutation. To be clear, Luxturna is only indicated for one of those 200 odd genetic subtypes. 

MW: Is it possible that Luxturna could work for the others?

JM: No, we wouldn’t expect that it would because it is targeted specific for RPE65. We know the bits and bytes of code that make up the RPE65 gene, and that’s what we’re delivering to the back of the eye.

MW: How do you actually deliver it? What is the process?

JM: Essentially, we use a disarmed virus. It’s something called adeno-associated virus, essentially something that causes the common cold. It’s not pathogenic. We strip it of some of its properties that would allow it to replicate in a way that you wouldn’t ideally want, but we keep the properties that allow it to be infectious. It is basically a carrier that ultimately delivers the genetic material, the correct copy of RPE65, to the cells in the back of the eye. The virus, or the viral-like particle, infects the cells and drops its DNA inside. Instead of dropping in the viral DNA, it drops in the normal copy of RPE65. It’s done through a surgical procedure and takes about 45 minutes. It is under general anesthesia and the surgeons do one eye at a time. About a week or so later, they’ll do the second eye.

With the scientific tools that we have today and the way the mode of action is working in these types of therapies-whether it be gene therapy, gene-modified cell therapy, or gene editing-I think we are headed to more specific therapies. The technology itself is very targeted, but that doesn’t mean the drug is necessarily aiming at a “specialty market.” 

I think one of the next phases for genetic medicine-gene therapy being one of those-is the broader application of these to many other types of disorders. For instance, we’re all very excited about some of the work that we see continually emerging in our lab around neurodegenerative conditions. We’re working on some rare conditions, diseases like Batten disease, but we’re also working on things like Huntington’s disease, which doesn’t have any disease-modifying treatment today and is actually one of the more prevalent conditions. 

You could also imagine applying this to an even broader spectrum of more common neurodegenerative conditions. If you think about the history of the last 20 or 25 years, we’ve tried to apply different technologies to various neurodegenerative conditions. One of the major issues has been the blood-brain barrier; we can’t repeatedly administer something systemically and get enough of it to cross the blood-brain barrier. What if you could take that concept and apply it directly to the brain through a one-time injection? It opens up real potential in a variety of different areas.

MW: Do you have any parting words for people in sales and marketing operations and in medical about how they can get themselves prepared for these developments?

JM: I think that this generation, this century of science, is going to force us into real creativity on how we ultimately commercialize. I would encourage everyone to think differently, to create new paths for how any of

these types of medicines come forward. They’re going to force innovations in one area that will also spill back over into other modalities that we might be using today. I think it just behooves people to start thinking about things on a different level of creativity than maybe we’ve done historically.