PC: MFN is not merely reshaping launch sequencing decisions: it has prompted companies to reconsider whether to launch in certain markets at all. The central consideration is the ability to contain MFN exposure on the US business – still the dominant value driver for most oncology assets.

Launch order itself is also directly impacted: high-complexity MFN markets such as Germany and Japan, as well as lower-volume MFN markets like Ireland and Norway, are increasingly being considered for delayed launch or de-prioritisation; non-MFN reference basket markets are attracting greater interest as earlier launch candidates.

PC: Optimal launch sequencing in oncology demands a combination of robust competitive intelligence and rigorous quantitative modelling.

Competitive intelligence is essential for tracking the evolution of treatment algorithms and standards of care. Pipeline surveillance alone is insufficient: intelligence must incorporate market-specific dynamics around reimbursement frameworks, prescribing restrictions, and realised net prices.

Quantitative modelling serves as the ultimate decision-making instrument, enabling scenario comparison across the full asset lifecycle value spectrum. Dedicated modelling layers are required to capture MFN risk exposure, in addition to the IRP dynamics already embedded in standard frameworks.

AC: The two most common mistakes I see are:

1. Companies do not model the IRA impact properly – both for their own product and also competitors.

2. Companies under-estimate the impact of contracting, an emerging threat in oncology, on their pricing, and think that oncology is only about efficacy and OS. Payers are increasingly bringing aggressive contracting in oncology. Look to the behaviour of BTK inhibitors.

AC: The US pricing environment provides heavy consideration for sequencing. The impact here is less from MFN and more from IRA. The trajectory of revenue and whether the indications are orphan designations impacts heavily here.

• If only orphan oncology indications are launched, then the product is exempt, and so a product with many orphan oncology indications may choose to prioritise only those over non-orphan if the revenue calculation comes out positively for such a path vs the loss from being selected under IRA.
• The cumulative revenue of indications will drive the product into IRA, so a company will want to carefully consider at what point an indication launch will accelerate entry into IRA and whether that entry, and any subsequent indications, will offset the loss from IRA selection.

There are many more considerations here, including small vs large molecule, the company’s size, and other factors, so the calculation is actually quite complex.

PC: Due to the highly competitive nature of oncology, there is a growing tendency to prioritise less competitive – 'blue ocean' – indications, as these are more likely to capture the attention of both HCPs and payers.

Beyond the benefit of lighter evidentiary requirements in less competitive indications, pursuing a highly competitive indication carries the additional risk of the standard of care shifting mid-trial, effectively triggering payer demands for more comparative evidence (head-to-head data, indirect treatment comparisons).

PC: Too late. Despite strategic challenges and potential missteps, inaction in the face of these challenges erodes asset lifecycle value while narrowing the therapeutic options available to patients and HCPs.

Early strategic planning, cross-functional alignment, and rigorous modelling can optimise sequencing and ensure that the evidence package available at launch is robust enough to withstand HTA scrutiny.

PC: MFN is the most immediate answer; JCA follows closely, now mandatory for oncology assets, it carries particular strategic weight for first-in-class products, where cross-market clinical evidence alignment is hardest to achieve.

A number of governments have grown more receptive to early access for innovative therapies, prompting companies to move these markets higher in the global launch sequence. The Middle East is a clear illustration of this trend.

AC: In addition to MFN and JCA, IRA is a major factor in assessing a multi-indication launch, along with the orphan status of indications, how closely competitors are coming in launch, and whether there is potential for the asset in combinations like ADCs to extend the lifecycle value.

I would assess all of these in the calculations above and beyond the playbook from 5 years ago, pre-IRA and pre-MFN.