Growing Mature Products After Loss of Exclusivity

I think pharma often starts managing mature biologics down too early. When a product is still clinically relevant and no credible biosimilar competitor is close to launch, I would want to understand why we are already reducing commercial support and putting lifecycle work aside.

IQVIA’s 2025 analysis identified 118 biologics expected to lose patent protection between 2025 and 2034. Only 12 had biosimilars in development in its June 2024 pipeline snapshot, leaving 106 in what it called the “biosimilar void.” The report estimated that competition for those remaining products could generate an additional $189 billion in U.S. healthcare savings. ¹

For an originator company, those findings should prompt a closer look at its own brands approaching loss of exclusivity. The expiry date belongs in the plan, alongside evidence about who is developing a competitor, how far that programme has progressed and when it could realistically launch. Those are different pieces of information, and they should lead to different investment decisions.

Growing a mature oncology brand after loss of exclusivity: the ERBITUX story

ERBITUX, or cetuximab, is a case I know well from leading marketed oncology products and later the oncology franchise at Merck KGaA. Its EU data exclusivity expired in 2014, and sales reached a low of €816 million in 2018. ^{2, 3} I drove the turnaround through market re-segmentation, access expansion and clinical partnerships that gave the product further opportunities to grow.

That work required looking closely at what was changing around the medicine. In colorectal cancer, new evidence was identifying patients for whom anti-EGFR treatment was particularly valuable. In China, reimbursement could allow many more patients to receive treatment. Other companies were developing medicines that could be studied in combination with ERBITUX. Each required a different commercial or partnering decision.

Re-segmenting colorectal cancer around tumour sidedness

The tumour-sidedness analyses emerging in 2016, including CALGB/SWOG 80405 and the CRYSTAL and FIRE-3 analyses, provided a stronger basis for focusing anti-EGFR treatment on appropriate patients with left-sided RAS wild-type metastatic colorectal cancer. These findings came from clinical researchers and cooperative groups, some working on trials Merck KGaA had funded, and they changed how the disease was understood. ^{4, 5}

I re-segmented our metastatic colorectal cancer strategy around that evidence and concentrated investment on left-sided RAS wild-type disease. Trying to maintain the same commercial focus across the whole market would have missed what the data were showing. I wanted the investment behind ERBITUX to reflect where the evidence was strongest and where the product could make the greatest contribution.

Tumour sidedness was subsequently incorporated into ESMO/JSMO guidance on first-line treatment, with an EGFR antibody plus chemotherapy preferred for appropriate patients with left-sided RAS wild-type disease. ⁶ For me, this is an important part of lifecycle management: continuing to understand the medicine better and adapting the strategy as the evidence develops, including when there is no new formulation or indication involved.

Expanding access through China’s NRDL

In China, I took direct ownership of the ERBITUX reimbursement resubmission and worked with the China organisation on the strategy. We accepted a lower price to reach a much larger patient population, and ERBITUX entered the National Reimbursement Drug List in 2018. Merck KGaA’s subsequent earnings releases identified the listing as a major driver of ERBITUX sales growth in Asia. ⁷

The commercial opportunity came from making an established treatment available to patients who previously had limited access. That deserves serious attention in a mature-brand review. A medicine can have years of clinical evidence behind it and still be far from reaching the patients who could benefit, particularly where reimbursement remains a barrier.

Lifecycle management through partner-funded combination studies: BEACON CRC

I also initiated and led collaborations that supplied ERBITUX to other companies for combination development. This allowed us to pursue lifecycle opportunities with partners funding and running the studies, rather than requiring every programme to be financed through our own development budget.

BEACON CRC illustrates the arrangement. Array BioPharma was the global sponsor, Pierre Fabre committed to funding 40% of the trial cost, and Merck KGaA supplied ERBITUX to trial sites outside the United States and Canada. ⁸ The partners could develop their assets in combination with an established medicine, while ERBITUX gained an opportunity to extend its clinical use.

This approach remained relevant well beyond the initial collaborations. In its 2025 annual report, Merck KGaA reported more than 270 active external clinical trials involving ERBITUX, including more than 40 Phase III studies. ⁹ For a mature product, that represents substantial continuing research without the originator having to sponsor every study itself.

Becoming a blockbuster after loss of exclusivity

ERBITUX crossed €1 billion in Merck KGaA’s annual sales in 2022, eight years after its EU data exclusivity expired. ^{2, 10} By 2025, sales had reached €1.176 billion, and the company continued to describe it as its best-selling oncology medicine and a standard of care in defined colorectal and head and neck cancer settings. ^{9, 11}

I am proud of that result and of the work behind it. Re-segmentation, reimbursement and combination development were all part of the strategy I drove with the teams. They created opportunities for a medicine that could easily have been treated as a declining asset simply because of its maturity.

What I would expect from a portfolio review

For a biologic approaching loss of exclusivity, I would expect the team to bring a view of the actual competition and the remaining opportunities for the brand. That includes the likelihood and timing of biosimilar entry, the return on continued commercial investment, and whether new evidence supports a more focused patient segment. I would also want access gaps and potential external development partners considered before concluding that further lifecycle investment no longer makes sense.

There are sound reasons to reduce investment when better treatments arrive, demand declines or the remaining opportunities cannot justify the cost. Equally, a clinically useful medicine with limited competition, unmet access needs and credible combination opportunities deserves a serious investment case. The decision needs to reflect those circumstances.

Leading portfolio management and strategy in our biosimilars business also made me attentive to the position a new entrant could realistically build. I never liked the argument for becoming the fifth or sixth programme behind a blockbuster simply because the reference product had large sales. The wider 118-molecule list is worth examining for mid-sized specialty biologics where being first or second could support a viable business. Some have been passed over because development costs or market conditions make them unattractive, but I would want to understand those economics before dismissing them.

With ERBITUX, I continued to pursue growth through better patient selection, broader access and partnerships. I would expect the same work to be done for other mature biologics before taking investment away from them. An exclusivity date, on its own, would not give me enough reason to stop.

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