When a phase 3 confirmatory trial by Southwest Oncology Group (ClinicalTrials.gov Identifier: NCT00085709) not only failed to show an improved benefit for gemtuzumab ozogamicin (Mylotarg™) in combination with chemotherapy in acute myeloid leukemia (AML) but also revealed major toxicity concerns, the drug was pulled from the US market in 2010, dashing hopes that patients with AML would finally have a new treatment.1

Despite the setback, clinical trials pressed on, evaluating the antibody-drug conjugate at lower, potentially safer doses and with various chemotherapy regimens.1 That persistence paid off in 2017, when the US Food and Drug Administration (FDA) granted full approval to gemtuzumab ozogamicin for adults with newly diagnosed CD33-positive AML and adults and children 2 years and older with relapsed or refractory CD33-positive AML.2

Away from the limelight, however, another study had been going on while the drug was off the market. At the FDA’s request, the manufacturer, Pfizer, had been providing the drug through an expanded access protocol (ClinicalTrials.gov Identifier: NCT02312037) to patients who were at least 3 months old who had relapsed or refractory AML, high-risk myelodysplastic syndrome, or acute promyelocytic leukemia (APL).3,4  As is standard in expanded access protocols, to be eligible for expanded access, patients had to have a serious or life-threatening disease — in this case, a hematologic malignancy — had to be ineligible for ongoing clinical trials, and had to have run out of treatment options.5

A total of 331 patients received the drug free of charge at 1 of 63 participating clinical sites in the United States between 2014 and 2017. The protocol was flexible, allowing patients to take the drug at lower doses and in combination with various chemotherapy regimens. In return, patients consented to have their outcomes collected and reported.5


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At the request of the manufacturer and with the aid of research funding, physicians collected and reported safety data for up to 60 days after the last dose was given and followed treatment-related adverse events until the event had resolved, returned to baseline, was deemed irreversible, or the patient died — all of which went beyond the adverse event reporting normally mandated in expanded access.5

Recently the data that were collected through this expanded access protocol were reported in Leukemia & Lymphoma — but something was clearly lacking.5

A New Purpose

Expanded access became an option for patients in 1987 when the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) crisis made it clear that patients with life-threatening conditions needed an avenue to access investigational therapies outside of traditional clinical trials.6

In all, there are 3 types of expanded access protocols, the most common 1 being when an investigational therapy is provided to individual patients. The second type provides an investigational therapy to an intermediate-size patient population, which is typically done for patients who do not qualify for ongoing clinical trials and may be initiated if FDA receives several expanded access requests from individual patients for the same use. The final type provides an investigational therapy to a larger patient population, under what is known as a treatment protocol.7

Although the goal of expanded access has always been to provide treatment to patients rather than to conduct research, that view has been evolving to include a secondary goal: data collection.

As Cancer Therapy Advisor previously reported, an emerging trend in drug development is the collection of data from patients in expanded access programs and use of these data to potentially support a regulatory approval. In other words, these data are being used for research — research that pharmaceutical company manufacturers are collecting but not necessarily making public or sharing fully.8

A study published earlier this year confirmed the trend, reporting an uptick in the number of FDA approvals that relied, at least in part, on expanded access data, and 4 cases of approved drugs for which expanded access data were the only data submitted to the FDA.9

In fact, third-party companies, such as WideTrial and myTomorrows, have emerged to help manufacturers run expanded access programs.

“We need to find some way to make expanded access a viable option to companies that don’t have the resources to do so,” said Alison Bateman-House, PhD, MPH, MA, assistant professor in the division of medical ethics at NYU Langone Health and co-chair of the Working Group on Compassionate Use and Preapproval Access, told Cancer Therapy Advisor.

In addition to coordinating expanded access programs, third-party companies are also collecting patient data as a form of real-world data. Referring to WideTrial and myTomorrows, Dr Bateman-House said, “I have no insight into either company’s financial models, so I endorse neither, except to say that innovation in this space may get us to a better situation overall.”