Faster drug development should be measured by whether patients are reached in time
By Garo Armen, PhD
Chairman and Chief Executive Officer, Agenus Inc.
The FDA’s Operation TrialBlazer initiative is being discussed largely through the lens of global competitiveness. The United States is moving to streamline drug development at a time when China and other countries are accelerating clinical research and attracting more biomedical innovation.
That concern is real. The United States should not accept unnecessary delay, unclear expectations or avoidable regulatory friction while other countries move faster.
But the deeper reason to modernize drug development is not national pride or industry competition. It is patients.
A faster system matters because people with life-threatening disease can run out of time long before credible evidence completes the final steps of the regulatory process. In oncology, that time is not abstract. It is the difference between being well enough to receive another therapy and being too sick to try. It is the difference between another chance and no remaining options.
The goal should not be speed for its own sake. Speed without evidence is not progress. It is risk. But evidence without urgency is also harmful, particularly when patients have serious disease and no satisfactory alternatives exist.
The standard worth setting is both at once: move faster because the evidence is strong enough to justify action, and preserve rigor by requiring confirmation.
The real test is whether patients are reached in time
Operation TrialBlazer includes important reforms: clearer expectations for early development, more efficient and urgent regulatory interactions, and greater willingness to consider the totality of evidence. These steps can reduce unnecessary delays and strengthen the U.S. development system.
But the measure of success should not be whether America simply moves faster than China. The measure should be whether American patients can access promising therapies with urgency that reflects patients’ needs.
That distinction matters.
In oncology, FDA already has tools to consider the totality of evidence in serious diseases. For many late-stage cancer patients, the issue is not simply whether FDA can accept one pivotal study or whether early development can be streamlined.
The more immediate question is whether existing pathways, especially accelerated approval, can be applied with urgency, consistency and rigor when the evidence supports it — including the views of a critical mass of experts who treat these patients every day.
Accelerated approval exists. It is not being used with the urgency patients need.
The United States does not need to invent an entirely new regulatory philosophy to reach patients sooner. It already has a mechanism designed for this purpose: accelerated approval.
Properly used, accelerated approval is not a shortcut around evidence. It is a disciplined way to allow earlier access for serious diseases with unmet need while confirmatory trials proceed. However, waiting for every final step of traditional development can deny patients access to therapies that may offer meaningful benefit while confirmation is still being generated.
The pathway is sometimes criticized as if it were a failed experiment. That critique misses the full record. Accelerated approval has delivered important cancer medicines to patients earlier than would otherwise have been possible. The answer is not to retreat from accelerated approval. The answer is to use it with greater discipline.
The cases that should raise concern are those built on thin initial signals and limited durability, poorly understood biology, or surrogate endpoints that do not meaningfully predict patient benefit. Those concerns should inform how the pathway is applied.
But they do not argue against accelerated approval. They argue for reserving it for the strongest cases: serious or life-threatening disease, no satisfactory treatment alternatives, durable clinical signal, coherent mechanism, manageable safety, and an active confirmatory trial designed to verify benefit.
That is the standard a faster system should reward.
For patients with no options, delay is not acceptable
For patients with refractory cancer where available treatments have failed, waiting is not a cautious default. It is a decision with consequences.
When a person with late-stage cancer cannot access an active investigational therapy, the alternative is often not a better or safer treatment. It may be more chemotherapy with cumulative toxicity. It may be radiation, surgery, a permanent colostomy, or hospice. In many cases, it is simply disease progression while administrative and regulatory processes continue.
This is particularly true in microsatellite-stable colorectal cancer, a disease that has historically not responded to conventional immunotherapy and where patients in later lines have limited or no viable options left. These patients often decline quickly. A delay of months can mean the difference between being eligible for treatment and being too sick to receive it. And when we compound these facts with more and more younger patients being diagnosed with metastatic colorectal cancer, the urgency for meaningful advances such as immunotherapy becomes a national priority.
Regulators and companies experience time as process. Patients experience it as a choice with irreversible consequences.
A modernized FDA should recognize that distinction. The goal is not to lower standards for patients with no options. It is to ensure that strong evidence reaches them before they lose the chance to benefit.
The United States needs a better bridge between trials and approval
The United States has mechanisms intended to help patients access investigational therapies outside clinical trials, including expanded access and Right to Try. These programs are important, but they are not enough and in most cases they do not work by offering desperately needed urgent intervention.
Right to Try does not require a sponsor to provide an investigational medicine. Expanded access can involve substantial physician coordination, institutional review, regulatory documentation, supply constraints and uncertain reimbursement. For smaller biotechnology companies, providing drug for free indefinitely can be financially untenable. For patients with advanced cancer, the time required to navigate paperwork and logistics can be clinically consequential. Some patients progress before access can be completed.
This creates an ethical and practical gap.
Other countries have recognized this problem more directly. France’s early-access framework, known as AAC, allows certain investigational medicines to be made available before full approval under defined criteria, physician oversight, national protocols, reimbursement and required follow-up.
The lesson is not that the United States should copy France’s system wholesale. The lesson is that access can be structured, regulated, data-generating and financially sustainable. Compassion and rigor do not need to be be opposites.
A serious modernization agenda should address this gap. Patients who have exhausted standard options should not have to depend on free-drug charity, fragmented compassionate-use requests, or their ability to navigate paperwork quickly enough before their disease advances.
BOT/BAL is one example of why this matters
At Agenus, we have spent years developing botensilimab plus balstilimab, or BOT/BAL, for patients whose tumors have historically been resistant to immunotherapy. Botensilimab is an Fc-enhanced anti-CTLA-4 antibody, and balstilimab is an anti-PD-1 antibody. Together, they are being studied across difficult-to-treat solid tumors, including microsatellite-stable colorectal cancer, ovarian cancer, sarcoma and others.
BOT/BAL remains investigational. It is not approved by the FDA. But the evidence generated to date is substantial and multidimensional. It is not a single isolated response signal.
Across more than 1,300 patients treated in clinical studies, BOT/BAL has shown evidence of durable activity in tumor types where conventional immunotherapy has historically had no or limited effect. Data have been presented at major medical meetings and published in peer-reviewed journals. The clinical signal has been observed across multiple tumor settings, multiple centers, and heavily pretreated patient populations, reducing the likelihood that it reflects a single-site anomaly or isolated patient-selection effect. In select patients results have been profound.
BOT/BAL has generated durable survival and response data in a population with few remaining options. In the neoadjuvant setting, short-course treatment has produced major pathologic responses in patients with resectable colorectal cancer, suggesting that the regimen may be engaging the immune system in a tumor type long considered resistant to immunotherapy. Across the broader program, the safety profile has been characterized, with immune-mediated toxicities such as colitis identified and managed through early, protocolized intervention.
This is the kind of evidence package that should trigger serious consideration under a disciplined accelerated approval framework: serious disease, high unmet need, biologic rationale, durable clinical signal, characterized safety and an active randomized confirmatory trial.
The question is whether patients who have no satisfactory alternatives should be required to wait for every remaining step when the evidence is credible, the disease is urgent and the confirmatory trial is already in motion.
International access shows the gap in the U.S. system
Physicians in the United States and outside the United States are already requesting BOT/BAL for patients who have exhausted available options. In France, BOT/BAL has been authorized under the AAC early-access framework in defined late-line settings, including microsatellite-stable colorectal cancer, ovarian cancer and sarcoma. Patients have also received access through named-patient programs in certain countries where such programs are permitted.
What these do show is that physicians treating patients with no remaining options see enough scientific and clinical rationale to seek access through regulated pathways. They also show that access can be governed, physician-directed and structured rather than improvised.
That contrast should matter to the United States. American patients should not be disadvantaged because our access mechanisms are either too fragmented, too slow or too dependent on whether a sponsor can absorb the cost of free drug.
If the United States wants to lead, it should lead first for patients, because competitiveness follows from moving strong evidence to patients sooner, not the other way around. Today the order is reversed. Treatments an American patient can obtain only by traveling to London or Zurich are already available to patients in those cities. Asking the sick to cross an ocean for access we could provide at home fails any standard of compassion, and any claim to leadership.
The call to action
Operation TrialBlazer should be the beginning of a broader modernization effort, not the endpoint.
FDA should clarify and apply accelerated approval with urgency in late-stage oncology when several conditions converge: serious or life-threatening disease, no satisfactory available therapies, credible evidence of durable clinical benefit, coherent biologic rationale, manageable and protocolized safety, and an enrolling confirmatory trial.
Policymakers should also examine how the United States can create a more sustainable access bridge for patients who cannot wait and cannot enter clinical trials. Such a framework should be narrow, evidence-based, physician-directed, financially sustainable and paired with real-world safety and outcomes collection. It should not weaken FDA standards. It should make those standards actionable before patients run out of time.
Companies have responsibilities as well. We must generate credible evidence, publish it, present it transparently, characterize safety honestly, complete confirmatory trials and avoid turning access into promotion. Patients deserve urgency, but they also deserve discipline.
At Agenus, we are committed to that standard. We continue to generate and disclose data and work within appropriate regulatory frameworks to help patients with no satisfactory options access investigational therapy responsibly.
The United States should not try to compete globally by lowering the bar. It should lead by proving that speed and rigor can coexist when evidence is strong, unmet need is urgent and confirmatory science is already in motion.
The purpose of modernization is not to win a race for its own sake. It is to reach patients in time and not lose sight of the goal: better outcomes, longer survival, and, where possible, cures.
Speed and rigor are not opponents. Together, they are how America should lead — by ensuring that patients who cannot wait are not left behind.