Big Pharma is betting billions on vaccines. Washington is making that bet harder to win.

Vaccines are going through a strange moment. On one side, the science is moving faster than it has in years, and pharma is putting real money behind it. On the other side, the regulatory ground in the US, the world’s largest vaccine market, keeps shifting under sponsors’ feet.

For anyone running clinical development, that combination raises a very practical question: how do you plan a multi year program when some of today’s assumptions may not hold by the time you file?

The Vaccine Business is Heating Up

If investment is any indication, large pharmaceutical companies still see a strong future for vaccines.

• Eli Lilly announced three vaccine acquisitions in May 2026: Vaccine Co., Curevo and LimmaTech Biologics. Together, the deals could be worth close to $4 billion. Lilly also hired Peter Marks, the FDA’s former vaccine chief, to lead its infectious disease business.
• Sanofi paid $1.15 billion for Vicebio in July 2025, gaining a non-mRNA combination vaccine candidate for RSV and human metapneumovirus. It also acquired Dynavax later in December 2025.
• GSK expanded the FDA approval of its RSV vaccine Arexvy in March 2026. The broader indication could make the vaccine available to an estimated 21 million Americans under 50 who are at higher risk of severe RSV disease.
• Moderna received FDA approval for mFLUSIVA (mRNA-1010) in August 2026, making it the first mRNA-based seasonal flu vaccine approved in the US. The vaccine was approved for adults aged 50 and older following strong Phase 3 results.

The message is clear. Major pharma companies are still putting money behind vaccines, while new products and technologies are expanding across RSV, influenza, pneumococcal disease and combination vaccines. The science is moving forward, and Big Pharma still sees vaccines as an important growth opportunity.

The US Rulebook Is Becoming Harder to Read

Over the past year, US vaccine policy has changed unusually quickly. One of the most consequential moves came at the CDC (Centers for Disease Control and Prevention).

Health and Human Services Secretary Robert F. Kennedy Jr. removed all 17 members of the CDC’s Advisory Committee on Immunization Practices (ACIP) and replaced them with a smaller panel, drawing criticism from scientists and public health organizations. In January, the CDC also reduced the number of universally recommended childhood vaccines from 17 to 11, prompting opposition from major medical groups and leading some states to follow their own guidance.

For vaccine developers, these changes have consequences beyond public health policy. FDA approval alone does not guarantee commercial success. CDC recommendations, insurance coverage, physician behavior and public confidence all influence whether a vaccine ultimately reaches patients.

The impact is already visible. GSK’s Arexvy received a broader FDA indication in 2026, expanding eligibility to high-risk adults aged 18–49. However, CDC recommendations have not yet been extended to this younger population, and the absence of a recommendation for repeat RSV vaccination continues to limit the vaccine’s commercial potential. Sanofi reported a 2.5% decline in vaccine sales in Q4 2025 and expects slightly negative growth in 2026, with executives pointing to declining vaccination rates and “confusion” in the US market.

The contradiction is striking: pharmaceutical companies are investing billions in new vaccine technologies just as the world’s largest pharmaceutical market is becoming harder to predict.

The courts have added another layer of uncertainty

These changes have not simply generated debate, several have already run into legal trouble.

In March 2026, a federal judge in Massachusetts issued a 45 page ruling that temporarily blocked the changes to the childhood immunization schedule and paused every decision the reconstituted ACIP had made since it was formed. The court found the government had likely bypassed the procedural and scientific review process required by law, and that the new panel appeared unqualified for the role it was assigned.

The dispute did not end with the March ruling. The administration appealed the injunction and later sought an expedited review, while the court order remained in effect. Months after the original policy changes, the legal and regulatory direction of US vaccine policy therefore remained unsettled.

The sequence now looks like this: federal policy changes, industry and the medical community react, courts intervene, and the policy landscape resets to uncertain again. For a company running a development program, the problem is not any single decision, it is the unpredictability of the cycle itself.

Moderna shows what regulatory uncertainty looks like in practice

Moderna’s mRNA flu vaccine mRNA-1010 offers a striking example. On February 3, 2026, the FDA declined to accept the company’s application for review, citing its use of a licensed standard-dose flu vaccine as the comparator. Moderna publicly challenged the decision a week later, arguing that it contradicted feedback received from the agency before Phase 3 and prior to submission.

The reversal came quickly. Following a formal meeting with Moderna, the FDA agreed on February 18 to review the application. In June, an FDA advisory committee unanimously supported the vaccine, and on August 6, the FDA approved it as mFlusiva for adults aged 50 and older. The pivotal Phase 3 trial included more than 40,000 adults and showed 26.6% higher relative vaccine efficacy than licensed standard-dose flu vaccines.

Why This Matters for Clinical Development

The broader lesson goes beyond any single vaccine. Regulatory expectations shape clinical trials long before a product reaches the submission stage.

Sponsors choose comparators, endpoints, patient populations and statistical plans years in advance. Once a pivotal trial is underway, many of those decisions are difficult or impossible to change.

If regulatory expectations shift before submission, a scientifically successful trial may no longer answer every question a regulator considers necessary. A different view of the comparator could require additional evidence. New questions about a specific population could mean another cohort or study. Additional safety requirements could extend follow-up and delay submission.

For large vaccine trials, those changes can have a significant impact on timelines, budgets and the overall development strategy.

This is why regulatory uncertainty needs to be considered at the beginning of clinical development, not only when a product is ready for submission.

Building Optionality Into Global Development

Sponsors cannot know exactly how regulatory expectations will evolve over a multiyear program. They can, however, reduce the program’s dependence on assumptions that may change.

In practice, that means:

• Design for more than one regulator

Consider FDA, EMA and other major regulatory requirements when selecting endpoints, comparators and study populations rather than building the entire program around one market.

• Build flexibility into the protocol

Where scientifically appropriate, allow for longer follow-up, additional cohorts or supplementary evidence if new regulatory questions emerge.

• Diversify recruitment geographically

A broader country footprint reduces dependence on a single market and provides alternatives if enrollment, policy or regulatory conditions change.

• Identify vulnerabilities early

Determine which assumptions in the protocol and evidence package would create the greatest risk if regulatory expectations changed before submission.

For international sponsors, running a separate clinical program for every regulator is neither necessary nor practical. A stronger approach is to build an evidence package that can support multiple regulatory pathways while drawing on recruitment markets that are not all exposed to the same risks.

A More Resilient Path Forward

The science behind vaccines remains strong, and investment continues to follow it. Scientific success alone, however, is not enough. Sponsors also need development strategies that can withstand changes in regulatory expectations.

At Cromos Pharma, we help sponsors connect regulatory strategy with protocol design, country and site selection, patient recruitment and evidence generation across multiple markets. Our global experience allows us to identify potential risks early and build clinical programs with the flexibility to adapt as regulatory expectations evolve.

In an environment where the rules may change during development, the strongest strategy is one that is built to adapt.