Pharma’s immunology field is full of blockbusters, and it’s just getting started

The value of the immunology space to the pharmaceutical industry is indisputable. There’s a reason AbbVie’s Humira sat atop the list of bestselling drugs for so many years and why many of the largest companies have a foothold in the therapeutic area — advances over the years have made “magic bullet” immune inhibitors a winning business prospect with a wide range of medical need.

And despite the crowded field of monoclonal antibodies designed to treat immunological diseases like arthritis, psoriasis, ulcerative colitis and Crohn’s disease, Big Pharma is still clamoring to bring the next big iteration to market. Earlier this month, Merck & Co. announced a $10.8 billion acquisition of Prometheus Biosciences, which holds phase 2 data for its lead molecule in patients with Crohn’s disease, reflecting the appeal of promising clinical candidates in immunology.

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“In the next three to five years, we’re going to see a lot of advances.”

Daniel Cua

VP and IL-23 pathway area leader, Janssen

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Often, success in the field breeds more success down the road. For example, as AbbVie faces more and more biosimilar competition to Humira, the company’s two updated brands — Skyrizi and Rinvoq — have begun to take up the mantle.

J&J’s pharmaceutical division Janssen has gone down a similar path, harnessing the interleukin-23 — or IL-23 — cytokine pathway with the blockbuster monoclonal antibodies Stelara and Tremfya. Overall, these and other immunology drugs work by blocking communication between immune cells and other cells, which is facilitated by proteins called cytokines, reducing the inflammation associated with these diseases.

Now, with Stelara facing a patent expiration this year, Janssen is readying its next-generation immunology prospects. Among the leaders of that effort is the “father” of this particular cytokine pathway who helped showcase its utility in the field — Daniel Cua, vice president and IL-23 pathway area leader at the company. Cua is also Janssen’s distinguished fellow for the pathway he helped discover, touting its benefits for patients and other scientists.

“The future is all about getting these drugs to as many patients as possible,” Cua said.

The rise of IL-23

Just getting the scientific establishment to recognize the IL-23 pathway as a viable immunology target was “an uphill battle,” Cua said of the beginning of his career at a small biotech near Stanford University, where he began to explore the space. Up to that point, most of the research had been focused on IL-23’s “older brother,” called IL-12 — but Cua and his team discovered that the two pathways shared an active receptor subunit p40 and that IL-23 could be a more specific target for immune pathology.

“That’s something that had never been demonstrated before, and I had the idea that when you target the p40 subunit, you can actually be affecting multiple cytokines,” Cua said. “It was confusing at the time, so our work clarified that it is IL-23 that’s driving most of the other immune inflammatory diseases.”

Since that time, investment in IL-12 has fallen by the wayside as IL-23 has soared on the wings of efficacy and low toxicity.

Now, Cua and his team at Janssen are looking for the next immunology drugs that can offer even more potent effects to patients while offering the greater convenience of a pill rather than an injection.

The company is also looking at a combination of IL-23 with the class of drugs called anti-tumor necrosis factor, or anti-TNF — Janssen brought the first anti-TNF drug to the market in 1998, which became the blockbuster Remicade. The combination of the IL-23 inhibitor Tremfya and anti-TNF Simponi could bring about a new wave of benefit for patients with immune diseases like ulcerative colitis. Two phase 2 studies of the combination therapy in ulcerative colitis and Crohn’s disease are among 25 clinical immunology programs at Janssen, including new uses for brands like Stelara and Tremfya, and a swath of novel compounds.

“In the next three to five years, we’re going to see a lot of advances,” Cua said.

The Prometheus promise

With immunology drugs reaching blockbuster status left and right, it’s no wonder analysts place the therapeutic area near the top of M&A prospects in the biopharma realm, behind only oncology and gene therapies.

Merck’s Prometheus acquisition puts the company in a unique position when it comes to immunology, according to Michael Levesque, a senior vice president and analyst at Moody’s Investors Services.

“Merck does not have presence as a leader in this market, although it does have a long history,” Levesque said, noting that the pharma giant collaborated with J&J on Remicade. Notably, Cua led the immunology discovery program at Merck before joining Janssen in 2019.

But Levesque pointed out that the expanding field of immunology still has room for more entries, even from the companies that haven’t made that a major focus of the last several years.