From Research Foundation to Biopharmaceutical Giant: How Vertex's 'Serial Innovation' Engine Drives the Next Blockbuster Drug

Vertex Pharmaceuticals is having its moment in the sun — and more than one.

Months after the approval of the first CRISPR gene-editing therapy, the company is also facing an FDA review decision for suzetrigine, a non-opioid painkiller with promising clinical prospects. Analysts believe the drugcould become a blockbuster. These two milestones show that its R&D-heavy strategy is yielding tangible results.

Meanwhile, Vertex's "cash cow" cystic fibrosis business remains strong. Its latest triple-drug combination candidatebeat its own blockbuster product Trikaftain clinical trials earlier this year. Along with earlier-stage kidney disease and diabetes programs, a focused R&D system supports a target portfolio that some may see as diverse.

Vertex's chief scientific officer, Dr. David Altshuler, attributes the company's rare success to several key decisions — decisions that solidified a strategy emphasizing "belief in targets" within a pipeline validated by biology.

Altshuler says Vertex holds a place among the few companies that have turned "serial innovation" into a successful model. He notes that of about a thousand biotech IPOs since the 1980s, only about 100 have discovered a new drug and advanced it all the way to market. About a quarter of those have done it twice. Only five companies have done it five times: Genentech, Amgen, Regeneron, Gilead Sciences, and Vertex.

Altshuler is a physician and human geneticist who worked on the Human Genome Project and co-founded the Broad Institute, serving as deputy director and chief academic officer. He has long believed that advances in genetic understanding could revolutionize medicine — but before joining Vertex, the industry was not ready to fully commit.

"By 2015 (when I became chief scientific officer), thousands of genetic contributors to disease had been identified. I believed some of them were useful drug targets, but no one in the industry was interested," Altshuler says. "I often consulted for biopharma companies; they found it interesting, but no one was willing to invest because there were no mouse models — there was risk aversion."

Altshuler found a home at Vertex. He says that here, risk is not avoided but confronted with scientific conviction.

A fateful decision

Vertex's path to its current position among biopharma success stories has been circuitous. In 2012, the company hit one of its most influential crossroads: its relatively new hepatitis C drug Incivek began facing competitors that could potentially surpass it clinically. Although Incivek became the "fastest drug to reach $1 billion in sales" less than a year after launch and made the company profitable, Altshuler says its prospects were precarious as new therapies threatened to "innovate past" Vertex.

At that time, then-CEO Jeffrey Leiden gathered Vertex leadership — including Altshuler, who was not yet employed but served on the board — to decide the company's future. It was at that moment that Vertex made cystic fibrosis its primary focus, betting that its drug Kalydeco, approved in 2012 (just before Leiden took office), could launch a product line that would change the treatment landscape for the disease.

"That year, we defined the R&D strategy we have today, and it is very simple: if you are going to invest disproportionately in R&D and only target serious diseases in specialty markets, you must succeed in R&D," Altshuler says.

To this day, Vertex maintains one of the highest R&D investment ratios in the industry, with more than70% of operating expensesallocated to drug development. In 2023, the company's R&D spending reached$3.7 billion。

In the years following Kalydeco's launch, dual-combination drugs including Orkambi and Symdeko received FDA approvals, followed by the triple-combination Trikafta in 2019, cementing Vertex's position as one of the world'sbest-performing biopharmaceutical companies. Trikafta brought in$8.9 billionin sales in 2023.

Although the success in cystic fibrosis sustained high revenue, Altshuler and his fellow scientists in the leadership circle — such as Leiden and Chief Operating Officer Stuart Arbuckle — saw the potential to leverage this fully committed strategy to build a stronger pipeline to tackle difficult diseases.

"Many people who came here during that period did not come because it was safe and proven, but because there was an opportunity to build something the industry had almost never seen — a company capable of serial innovation," Altshuler says.

The Vertex model

Leiden retired from the CEO position in 2020 and was succeeded by Dr. Reshma Kewalramani. Altshuler says Kewalramani now leads Vertex with the conviction that has become the company's brand. Although the pipeline includes different drug modalities and disease targets, the overall strategy and approach remain "highly consistent."

"We are not driven by therapeutic areas or platforms — we have a strategy that everyone understands, and it is about product quality and probability of success," Altshuler says. "This builds commitment... understanding of science and medicine matters more than domain expertise."

In the same year Altshuler joined Vertex as chief scientific officer, the companyestablished a partnershipwith CRISPR Therapeutics to develop drugs whose targets were not yet defined at the time. That collaboration ultimately led to Casgevy, approved late last year to treat sickle cell disease, and subsequently approved for beta-thalassemia.

Although the approval of Casgevy is historic as the first CRISPR drug, Altshuler views it from a different perspective. Rather than emphasizing the technology itself, he focuses on treating the disease.

"This industry has too much hype about technology, like Silicon Valley, always thinking the next novel gadget will change the world," Altshuler says. "What changes the world in medicine is understanding a disease and knowing how to address it. CRISPR is a very powerful tool, but once you have a target, there are multiple paths to get there."

Still, building on Casgevy's regulatory success, Vertex and CRISPR "learned a lot about manufacturing, how to run trials, and how to work with regulators," Altshuler says. This could benefit more disease targets, such as Duchenne muscular dystrophy, from gene-editing tools.

The next milestone

When scientists like Altshuler or Vertex's head of cystic fibrosis research, Fredrick Van Goor, invest so much of their lives in R&D success, the results can be emotional, Altshuler says.

He recalls the moment in 2017 when positive late-stage data for the cystic fibrosis drug Trikafta came in. Van Goor was on vacation on a boat in the Mediterranean with his family, and Altshuler called to tell him the news. Altshuler initially thought the sea wind was too strong for him to hear clearly, but in fact, the researcher who had worked on the program for 17 years was crying on the other end of the line.

"You don't know if you can do it, and then suddenly it becomes visible — no longer an abstract concept," Altshuler says. "This was the first project that made me think, 'Wow, you can actually do this.'"

Now, as the company advances its rolling submission for suzetrigine (planned forcompletion mid-year), Vertex is approaching its next major milestone — potentially a blockbuster breakthrough in treating acute and neuropathic pain. The drug, developed under a clear genetically validated approach, has already achievedtwo Phase 3 victoriesearlier this year. Its development also traces back to the company's roots in cystic fibrosis. In fact, both programs originated from the vision of Dr. Paul Negulescu, who has led Vertex's San Diego research center since 2003.

"Pain feels to me like CF did when I first came to Vertex in 2012," Altshuler says. He notes that when genetic targets become clear, drugs can grow from that knowledge, rather than the reverse — which often leads to project setbacks.

"Most drugs fail not because the drug itself is bad, not because the patients are wrong, not because the FDA is harsh, but because the target hypothesis is not relevant to the patients being treated," Altshuler says. "If you look at truly transformative drugs, they are often rooted in human biology. So we decided to only study topics where the causal human biology is clear."

Altshuler says that because the strategy focuses on disease biology, Vertex must remain open to multiple modalities.

"Our hypothesis is that if you focus on targets with clear causal human biology (rather than symptomatic or reactive), and use whatever tool is appropriate, you can succeed in R&D with a higher success rate," Altshuler says.