The planned exit of longstanding Pfizer CSO Mikael Dolsten comes at a pivotal moment for the huge drugmaker. The Covid-19 vaccine aura has fully worn off, it’s made a spate of deals to reload its pipeline, and a handful of top executives have been replaced.
It’s likely to take until next year for Pfizer to have a replacement as it mounts an external search. But when they arrive, they’ll face a handful of important issues that are likely to determine the future of the company’s R&D efforts and products.
1. How can Pfizer shore up its obesity pipeline?
It’s the question that really every pharma outside of Lilly and Novo Nordisk is asking. But it’s arguably most important for Pfizer, which has three weight loss agents in Phase 1 studies. That includes a trial testing its lead candidate, danuglipron, as a once-daily drug after a twice-a-day trial reported high discontinuation rates last year. But those drugs are still early, and the field is full of competitors — some of which are likely to be for sale. While Pfizer CEO Albert Bourla has said the company is looking to catch its breath after pouring billions into M&A in the last couple of years, a chance to move faster in obesity may be too tempting for a company like Pfizer to ignore.
Danuglipron should get a data update within weeks, Bourla said at an investor conference last month, and the drug’s results in the Phase 1 trial will either hand the new R&D leader some momentum or a cleanup job.
2. Does it want to try and make mRNA a big business outside of vaccines?
Look across the biotech world, and there’s no shortage of startups focused on new ways to wield mRNA-based products in cancer, cell therapies, gene editing and more. That includes two of Pfizer’s Covid-19 vaccine peers, Moderna and BioNTech, both of which have major programs in oncology.
But three and a half years since Pfizer’s mRNA-based Covid-19 vaccine transformed the company, Pfizer has little application of mRNA in the clinic beyond new vaccines, namely for flu and chickenpox and related combinations with a protein subunit RSV candidate (any of which, to be sure, could be huge products).
There’s still plenty of work to do to prove how big mRNA can be outside of vaccines. Many other companies are already making those bets, however, and Pfizer’s new science head will need to decide if they want to as well.
3. How big will Pfizer’s aspirations be in gene therapy?
A year ago, Pfizer sold off a portfolio of early-stage gene therapy candidates for rare disease to AstraZeneca in a deal worth up to $1 billion, plus potential tiered royalties. It also recently canned a Phase 1 stage Wilson disease treatment from Vivet Therapeutics.
But it held on to a late-stage gene therapy for patients with Duchenne muscular dystrophy, a market dominated by Sarepta — only to report that the treatment failed to improve motor function in younger boys and flunked other key secondary endpoints.
Its gene therapy decisions look a lot like its choices in mRNA. There’s an explosion of work in biotech targeting genetic diseases, and Pfizer has proven it can bring gene therapies to market — it’s one of just two companies with an approved gene therapy in the US to treat the bleeding disorder hemophilia B, and it has a late-stage candidate to treat hemophilia A as well.
But does it want to keep pursuing the high-risk area, where the science seems to sometimes be evolving faster than the business models?
4. How will cost cuts impact R&D?
Just when it seemed that Pfizer was at the end of a $4 billion cost-cutting effort announced last year, a fresh round of cuts was announced in a securities filing in May. A Pfizer spokesperson said at the time that the new $1.5 billion reduction effort would center on manufacturing efficiencies and “product portfolio enhancements.”
But following the company’s spree of acquisitions, a new R&D head is almost certain to look across the portfolio to make choices about new priorities (as will Pfizer’s newly-hired head of portfolio strategy, Andrew Baum).
5. How far do its ambitions stretch in oncology?
Pfizer’s $43 billion bet on Seagen, plus its existing portfolio of cancer treatments, made clear that it’s making moves to be a premier oncology company. But it’s still not quite at the level, revenue-wise, of AstraZeneca and Johnson & Johnson, the two pharmas directly ahead of Pfizer in global oncology revenue.
In the first quarter of 2024, the first time Seagen’s products were factored into earnings, Pfizer reported $3.55 billion in oncology sales. J&J, for comparison, reported $4.8 billion. And AstraZeneca, which years ago walked away from a deal with Pfizer and bet on its own oncology pipeline, reported $5.1 billion.
Help could be on the way, however. Pfizer boasts 20 ongoing Phase 3 oncology programs, spanning new label additions and new molecular entities. By 2030, the pharma anticipates it will have eight blockbuster drugs in the oncology portfolio.
6. Can an outsider pitch a vision that shareholders will buy?
Pfizer is in some ways trapped by its own size — it’s so big that it’s hard for any one product to make a huge difference (Covid-19 being the exception). And there’s a long-running joke that the company’s shares are trapped by some gravity that keeps them hovering right around $30.
Leadership changes aren’t just about a new person in the seat. They’re a chance to reset how people (inside and out) think about Pfizer. And the new R&D chief — who Pfizer says will likely come from outside the company — won’t just have to make science decisions. They’ll have to sell a vision for the company’s labs that’s bigger than any one molecule or trial.