Ron Philip, Spark Therapeutics chief operating officer, who will ascend to CEO on April 1

More than four years after leading Spark Therapeutics to market with the first gene therapy for a genetic disease to win FDA approval, Jeffrey D. Marrazzo is preparing to step down from the Roche subsidiary’s helm and take his career in a different direction.

Marrazzo is preparing to hand the proverbial reins to Spark’s chief operating officer Ron Philip, five years after he joined the company as chief commercial officer. As COO, Philip leads product strategy development and execution for early and late-stage pipeline assets, and also oversees the company’s commercial operation.

Philip’s promotion to CEO takes effect April 1.

“I don’t plan to join another company as a CEO but, rather, to work with multiple leaders and founders on helping them chase their visions, in order to really multiply my own impact, and take my experience and translate it to other organizations,” Marrazzo told GEN Edge.

Does that mean a consultancy is in his future? “Not necessarily,” Marrazzo replied. “Stay tuned for what it might look like.”

Marrazzo was Spark’s founding CEO, presiding over its creation in 2011 as a research center within the Children’s Hospital of Philadelphia (CHOP). Two years later, Spark was spun out of CHOP’s Center for Cellular and Molecular Therapeutics with a $50-million Series A financing.

Spark has grown into a fully integrated, commercial gene therapy company, employing more than 800 people—about half of whom have joined in the past two years or so since Spark was acquired by Roche for $4.8 billion.

Marrazzo led Spark’s capital-raising efforts, garnering more than $1 billion in financing before the company went public in 2015, when it completed an initial public offering that generated $168.9 million in net proceeds after being upsized from an initial $86.25 million IPO.

Perhaps most important, Marrazzo headed Spark’s successful effort to bring to market Luxturna® (voretigene neparvovec-rzyl), an adeno-associated virus vector-based gene therapy which won FDA approval in 2017 as a one-time treatment for children and adults with the rare inherited blindness disorder biallelic RPE65 mutation-associated retinal dystrophy, following an advisory committee’s unanimous recommendation.

Defending pricing

Luxturna—which is marketed in the European Union by Novartis—has generated criticism because of its list price of $850,000, or $425,000 per eye treated. Spark has defended its pricing by noting the company’s efforts to broaden patient support and other patient support services associated with the gene therapy.

Spark also agreed to share risk with some payers by agreeing to pay rebates if patient outcomes failed to meet short-term efficacy (30-90 days) and longer-term durability (30 months) measures.

Philip and colleagues developed and oversaw Spark’s distribution and reimbursement model for Luxturna while he served as Spark’s Chief Commercial Officer from 2018 until last year, when he was named COO. Philip joined Spark in 2017 as senior vice president and head of the company’s Global Commercial operation.

“We haven’t had any patients that wanted to get treatment that didn’t get treatment because of costs,” Philip said. “We put forward solutions that really got the marketplace comfortable and I’m talking about not only just insurers but doctors, as well as patients around the business of gene therapy and what it meant.”

“What we did, with Luxturna gives you a perfect window into what we would do for future therapies,” Philip added.

Philip noted that Spark belongs to a public-private coalition formed in October to address the future of gene therapy, the Bespoke Gene Therapy Consortium (BGTC). This is part of the NIH Accelerating Medicines Partnership (AMP) program managed by the Foundation for the National Institutes of Health (FNIH).

“We’re confident that all of the efforts that we’ve done in the past and that we’re currently doing is going to set the stage for making sure that therapies that we’re bringing forward, which are 21st century kind of medicines, that we have a 21st century model that can support the actual use of those medicines.”

Luxturna generated $27 million in net product sales during 2018, its first full year on the market. That success, plus Spark’s ability to develop a pipeline of gene therapies, attracted Roche’s attention. In 2019, Roche acquired Spark for $4.8 billion cash, in a deal that expanded the Swiss pharma into gene therapy.

Roche has stopped providing annual sales figures for Luxturna, which reportedly climbed to $38 million in 2020. “Spark Therapeutics’ proven expertise in the entire gene therapy value chain may offer important new opportunities for the treatment of serious diseases,” Roche CEO Severin Schwan stated at the time.

Among companies looking to seize those opportunities is MeiraGTx, which in January received a $30-million milestone payment from Janssen Pharmaceuticals after it began dosing patients in the Phase III Lumeos trial (NCT04671433) assessing its gene therapy candidate botaretigene sparoparvovec (AAV-RPGR) in another inherited retinal disease, X-linked retinitis pigmentosa (XLRP).

MeiraGTx and Janssen are among companies striving to develop gene therapies for XLRP. Also in that category is Applied Genetic Technologies Corp. (AGTC), which plans during the second quarter to release interim three-month data from its Phase II SKYLINE expansion study (NCT03316560) of its lead gene therapy program AGTC-501.

Long-term thinking

Roche’s buyout ended Spark’s years as a public company—something Philip said has proven beneficial given its focus on gene therapy.

“It really gives us the time and space to think long term about a strategy and go out and execute it. I think that’s really needed in the gene therapy space,” Philip said. “As you think about where the science is going and where the platform needs are, you really need to provide ample space and time to let the strategy actually play itself out. I think that’s what we’ve been doing on top of scaling the company responsibly.”

Under Marrazzo and Philip, Spark has built a pipeline anchored by two Phase III programs: Fidanacogene elaparvovec (SPK-9001) for Hemophilia B, now overseen by Pfizer with Spark standing to gain royalties; and SPK-8011 for Hemophilia A.

SPK-8001 generated positive Phase I/II data published in The New England Journal of Medicine in November. The data showed that at a median efficacy follow-up of 33.4 months, 16 of 18 participants showed sustained factor VIII (FVIII), allowing for a halt to prophylaxis and a reduction in bleeding episodes.

Also in Spark’s pipeline are two Phase I/II programs: SPK-8016 for Hemophilia A with inhibitors, and SPK-3006 for Pompe Disease. The rest of Spark’s pipeline is preclinical and includes gene therapies for:

  • Hereditary angioedema, Huntington’s disease, and an undisclosed indication (all in candidate optimization/IND-enabling phases);
  • Stargardt disease and another undisclosed indication (both in discovery phases).

Given its workforce and accomplishments, Spark is an anchor of the sub-cluster of some 45 cell and gene therapy companies that has emerged in Greater Philadelphia—No. 7 among the “Top 10 U.S. Biopharma Clusters” as ranked by GEN.

In December, Spark announced plans for a $575-million gene therapy innovation center in Philadelphia, within Drexel University’s campus in the University City neighborhood. The 500,000-square-foot center is designed to serve as a Roche global center of excellence for gene therapy manufacturing, facilitating collaborations with Drexel and other stakeholders in the region. Construction of the center is anticipated to begin later this year.

“The primary thing we’ve been focusing on since then is the process of moving from conceptual designs to more detailed designs and working through the permitting process,” Marrazzo said. “We do expect that things are still on track, and expect in the second half of the year, possibly the third or fourth quarter is when we try to break ground and that project gets underway.”

Conceiving the company

The innovation center is expected to emerge a decade after Marrazzo and other co-founders first conceived of Spark.

“In 2011, a handful of us dreamed that we could create something special. Together with [Steven M.] Altschuler [MD] and [Katherine] High [MD], who I had the great fortune to partner with in creating Spark, we spun promising gene therapy research out of the prestigious Children’s Hospital of Philadelphia (CHOP) with a mission to bring one-time, curative therapies to patients,” Marrazzo recalled in a farewell letter issued Wednesday to Spark employees.

Altschuler formerly chaired Spark’s board and today serves a managing director-healthcare ventures at Ziff Capital Partners and chairs the board of 89bio in San Francisco.

High served as Spark’s President, Head of Research and Development, and a member of the Board of Directors at Spark, where she directed the development and regulatory approval of Luxturna. She is now President, Therapeutics for AskBio, a subsidiary of Bayer focused on developing gene therapies.

Before joining Spark in 2017, Philip held several senior leadership positions at Pfizer, including Regional President for Africa/Middle East, Head of Global Business Unit Strategy, Head of Business Development Search and Evaluation and Commercial Development Lead within Pfizer’s Innovative Products Business.

Earlier, Philip worked in U.S. commercial operations for Wyeth Pharmaceuticals, which Pfizer acquired in 2009—as well as with Deloitte Consulting in its strategy and operations practice, and at Merck and Co.’s manufacturing and marketing divisions.

“[Ron Philip] launched the first gene therapy for a genetic disease. He’s led our portfolio governance committee the last two years. And he has been with me for the last five years working on the company and understands the culture of it, understands the importance of the company in Philadelphia, and so many other things,” Marrazzo said. “It’s really an ideal way to hand over the reins to Ron.”

“A Great Training Ground”

What convinced Philip that the time was right to move into the proverbial corner office?

“I think the moment started a couple years ago, when I started to chair the portfolio process at Spark,” he replied. “As I got much closer to the pipeline assets, it was basically a great training ground for me to get much closer to the other functions that I wasn’t privy to before, when I was primarily on the commercial side.”

By chairing Spark’s portfolio governance committee, Philip said, he was able to get closer to R&D as well as manufacturing. His confidence grew, he said, with Spark’s progress on its pipeline: “We could tangibly see the impact from the decisions that we were taking the investments that we were making.”

Once Spark was acquired by Roche, he continued, the company was better able to parallel track a variety of different programs and work on its platform.

“All of those things really gave me the confidence that I was learning the ins and outs of the various functions as well as, obviously, having an impact on moving products closer to patients,” Philip said.

“Working with Jeff for the last five years, I’ve picked up a few things that obviously I will continue to utilize going forward into the next chapter. All of it is just a combination that you get to a point in your career where you’re ready—and I think this is the point.”

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