Therapeutic cancer vaccines appear poised to become the next innovation to revolutionize standard of care in oncology, building on the trail blazed by immune checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapies and now antibody-drug conjugates (ADCs). While cancer vaccines have faced setbacks in the past decades, better understanding of tumor biology and technological advancements—for example in genetic sequencing, artificial intelligence and machine learning and mRNA vaccine platform development—are enabling fresh successes and triggering well-earned enthusiasm for this treatment modality.

With more than 400 current cancer vaccine trials across a wide range of indications (Figure), there is a palpable surge in the commitment to bringing these transformative therapies to patients. As with other recent therapeutic innovations, manufacturers will face pressure from payers to justify the high prices cancer vaccines are likely to command compared with existing options. For companies with cancer vaccines in their pipelines, now’s the time to consider how today’s development decisions will affect tomorrow’s perceptions of value and price.

In theory, therapeutic cancer vaccines are most effective in adjuvant or minimal residual disease settings, where the tumor load is comparatively lower and immunosuppressive mechanisms are less firmly established. However, a significant proportion of cancer patients are diagnosed in later stages (82% of lung cancers, 63% of colorectal cancers and 89% of pancreatic cancers are diagnosed in late stages), at which point a vaccine alone may be ineffective. Adding to the challenge, demonstrating clinical differentiation and value can be challenging in early stages given the availability of multiple established treatment modalities.

So, what strategies should manufacturers prioritize to build a differentiated value narrative for their cancer vaccines in early versus late stages?

Targeting early stages. For indications for which patients are typically diagnosed early, demonstrating clinical superiority against an established standard of care can be challenging. Manufacturers should be prepared to conduct head-to-head trials against existing therapies, particularly when seeking market access outside the U.S., where regulators demand clear evidence of differentiation to justify high price tags.

To strengthen value, some manufacturers are exploring the use of cancer vaccines as an add-on to standard care. This strategy aims to enhance outcomes by offering a more comprehensive and potentially more efficacious treatment plan for patients.

Mature overall survival (OS) data remains the gold standard for reimbursement decisions outside the U.S., but generating it for vaccines targeting early-stage cancer will be challenging—regardless of whether a company is pursuing a vaccine monotherapy or one for use in combination with an established drug. This is because a treatment’s impact on OS may only become evident after extended follow-up. The heterogeneity of early stage populations only further complicates interpretation.

In this context, it becomes essential to leverage early advice meetings with payers, whenever possible, to explore alternative, patient-relevant endpoints. The FDA’s recent recognition of minimal residual disease (MRD) as an acceptable endpoint for accelerated approval in multiple myeloma demonstrates a step in the right direction.

In addition to demonstrating value from the outset, manufacturers should also focus on market-shaping activities such as promoting early screening to ensure all eligible patients are considered for cancer vaccines early enough for them to be effective. Given the limited window for treatment initiation, educating physicians on vaccine eligibility criteria will also be key to ensuring they are equipped to make timely, appropriate treatment decisions.

Targeting relapsed and refractory settings. While unmet need for patients whose cancer has either returned or not responded to other treatment options is high, demonstrating clinically meaningful efficacy in late-stage cancers can be difficult. The main challenge arises from the presence of a well-established tumor microenvironment, with a high degree of immunosuppression, that prevents cancer vaccines from reaching their targets. To clear this hurdle, manufacturers can leverage the synergistic effects of combining cancer vaccines with therapies proven to disrupt the tumor microenvironment. Indeed, a number of clinical trials are looking to turbocharge patients’ immune responses by studying vaccines in combination with immune checkpoint inhibitors.

The majority of therapeutic vaccines under development are being studied together with branded PD-1/L1 checkpoint inhibitors, making for a pricey combination therapy. While the first generation of these drugs is set to face biosimilar competition starting in 2027, they are likely to be supplanted by follow-on agents such as bispecifics and next-generation biologics targeting biomarkers other than PD-1/L1. Regardless of the combination, the resulting regimens are likely to have a significant impact on payer budgets, particularly if addressing larger early indications. These combinations may push the boundaries of what payers are willing to cover.

Although combination therapies cost more than monotherapies, they do not always increase value in proportion. This discrepancy has led to negative value assessments in the EU, with regulators rejecting more than one in three combination therapies between 2011 and 2020—roughly three times as often as they have for monotherapies. So, how should manufacturers navigate the complex issue of access and affordability for future cancer vaccines?

One potential solution lies in alternative contracting schemes with an emphasis on simplicity, given payers’ aversion to more intricate agreements. While manufacturers have explored risk-sharing models in the past, their design and execution complexities have often proved insurmountable. As an alternative, manufacturers could collaborate with payers to create transparent and manageable models. Examples include:

• Amortization models. These allow for the cost of a treatment to be spread over a certain period of time, helping to defray the high upfront cost of treatment.
• Coverage with evidence generation. In this model, the manufacturer and payer agree to cover the cost of a treatment while evidence is being generated about its effectiveness. If the treatment meets an agreed upon efficacy threshold, the payer will continue to cover its cost. If not, the manufacturer may be required to refund all or part of the cost of treatment.
• Subscription models: In this model, payers agree to pay a fixed amount per month for access to a treatment. This provides a predictable revenue stream for manufacturers while making high-cost vaccines more accessible to patients.

Manufacturers have successfully implemented each of these agreement types for other expensive therapies, so they provide potentially viable models for costly cancer vaccines.

Individualized neoantigen therapies (INTs) are emerging as one of the most promising candidates in cancer vaccine development. Unlike traditional cancer treatments, which tend to be one size fits all, INTs are tailored to each patient’s unique tumor mutational signature, making them highly personalized.

Given that they’re designed to attack a tumor’s unique genetic variations, INTs offer the potential to stimulate a stronger and more effective immune response. By targeting neoantigens, which are “new” antigens not found in a patient’s normal cells, these vaccines can help the immune system more accurately identify and attack cancer cells while sparing healthy cells. This could potentially lead to more effective treatments with fewer side effects.

Several strategic partnerships have been established recently to accelerate the development of neoantigen vaccines. In 2016, the Parker Institute for Cancer Immunotherapy—in collaboration with research institutes, nonprofits and the pharma industry—launched the Tumor Neoantigen Selection Alliance (TESLA) to boost the development of breakthrough immune therapies, including cancer vaccines. And in January 2023, the U.K. government signed a memorandum of understanding with the biotech firm BioNTech to accelerate clinical trials for personalized mRNA immunotherapies, with the goal of providing personalized treatments for up to 10,000 patients by the end of 2030—either in clinical trials or as approved treatments.

The development and delivery of INTs, however, pose unique challenges. Identifying neoantigens, manufacturing a custom product and delivering it to patients is a complex, time-consuming and expensive process. The logistics of storing and administering these INTs, which often require cold-chain storage, present additional hurdles. So, how should INT manufacturers think about distribution to encourage widespread access to these treatments when they become available?

Given that side effects from INTs are expected to be more manageable than those associated with CAR-T infusions, it should be feasible to administer them on an outpatient basis in community settings. This will become relevant because some INTs will be paired with other therapies, such as checkpoint inhibitors. Leveraging existing infrastructure for these combined therapies, and complementing it with tailored support, will be key to facilitating widespread uptake.

INT manufacturers will need to navigate three challenges:

Logistics. Storage of multi-dose INT vaccines will present a significant challenge, so manufacturers should be prepared to provide logistical support. Providers with robust ultra-low-temperature storage capabilities may only need help handling the increased patient load. Those with more limited resources, meanwhile, may need to turn to third-party services to help overcome logistical complexities. Many third-party logistics companies and specialty distributors have local storage solutions, but manufacturers will need to tailor distribution models to overcome logistical challenges and contract appropriately with providers to minimize burden.

Liability. Multi-course therapies introduce compliance risks and raise questions about who’s financially responsible for unused product, for example if patients fail to complete their full course of treatment. Determining the party responsible for the product post-manufacturing will be crucial, especially for multi-dosed INTs.

Provider economics. While gene therapy manufacturers have been partnering with specialty pharmacies to support logistics and alleviate cash-flow risks associated with expensive therapies, this model may not work for everyone. Some providers likely will prefer the buy-and-bill model, allowing them to directly manage procurement and reimbursement, enabling better cost control and potentially enhancing financial performance.

For INTs to achieve widespread uptake, manufacturers will need to offer a range of flexible distribution models tailored to meet the unique needs and capabilities of various providers. By offering a range of flexible distribution models, INT manufacturers can help facilitate the smooth integration of these medicines into the existing provider ecosystem.

In 2010, the National Breast Cancer Coalition (NBCC) set an ambitious goal of developing a preventive vaccine for breast cancer by 2020. Four years after their deadline, the only preventive cancer vaccines we have are for those targeting virus-induced cancers like Hepatitis B and HPV. However, the landscape is changing, with trials focused on patients at risk of developing cancer or preventing relapses in those in remission showing promising early results.

While we’re not there yet, these developments suggest a potential paradigm shift in oncology away from treatment and towards prevention. Preventive vaccines could become an important part of a multifaceted approach to cancer management. As research advances, integrating preventive strategies into the standard of care could become a realistic goal, contributing to a more comprehensive and proactive approach to cancer care.

Even without preventive cancer vaccines, the advent of therapeutic cancer vaccines places oncology on the cusp of a paradigmatic shift. While demonstrating value, establishing appropriate pricing frameworks and ensuring equitable access create challenges, the potential for these vaccines to revolutionize cancer care is immense. The journey ahead is complex, but the promise is undeniable, as the rewards could be life changing for millions of patients around the world.