A Promising Move Toward Compassionate Access to Drugs

Andre Goy, MD

Editor-in-Chief of Oncology & Biotech News

Chairman and Director Chief of Lymphoma Director, Clinical and Translational Cancer Research John Theurer Cancer Center at Hackensack University Medical Center

On the tail of AACR last month and ACSO coming up at the end of this month, the continued transformation happening in oncology reverberates more and more loudly. As I have reviewed several times in this column, the changes occurring in cancer are unprecedented and will have profound impact. This goes across the board, from novel therapies—small molecules targeting the BCR pathway, such as BTK or PI3K inhibitors (which are changing the field in CLL and likely in MCL), second- or third-generation EGFR inhibitors targeting resistant variants in lung cancer, and BRAF inhibitors in melanoma or hairy cell leukemia, just to name a few—to the amazing development of checkpoint inhibitors (melanoma, lung cancer, Hodgkin lymphoma) and the entire field of cell therapies with CAR-T cells and derivatives.

In many instances, these changes are so dramatic that physicians and patients want access to such compounds or technologies before they receive regulatory approval. Unfortunately, accessing these promising therapeutics can be difficult. Many of the sickest patients with refractory disease do not qualify for clinical trials. Furthermore, entire new paradigms can sometimes develop through the use of unapproved drugs, as illustrated by the thalidomide story in multiple myeloma, where it was first used off study, out of despair in a patient with refractory disease (based on its all-too-well-known antiangiogenesis effect, explaining deformations seen in newborns). The initial results were so impressive that it opened an entire new field with IMiDs in a variety of malignancies.

Mechanisms to gain access to nonapproved drugs exist through the expanded access programs, commonly referred to as “compassionate use.”

The process to make this happen is typically very complicated, involving both the sponsor and FDA, as well as local IRBs. In most cases, however, such requests are denied for a variety of reasons.

The complexity of the issues at stake resides in the multiple aspects involved, from ethical questions to regulators’ concerns over liabilities for allowing access to unapproved drugs. I believe an important step forward was recently made when Johnson & Johnson (J&J) announced its plans to create a Compassionate-Use Advisory Committee (Comp-AC) to streamline and organize this process.

The CompAC committee will consist of 12 members, including doctors, bioethicists and patient representatives. This committee will independently examine all requests submitted (online or through a toll-free hotline) in a timely manner and then render an opinion to J&J.

Although CompAC received positive coverage across the world, including on the frontpage of The New York Times, some critics have emerged arguing that this will not truly help in practice. Concerns mentioned include how many cases will actually benefit (ie, “not everyone can benefit…”), what eligibility criteria will be used, and can a pharma-sponsored bioethics board fairly decide who receives experimental drugs? Others have suggested that before forming an independent, national advisory board, requests at-large for all experimental drugs that appear very beneficial in early trials should be reviewed.

Though compassionate use remains a complex societal issue, I applaud the initiative of J&J to at least offer a first step. If successful, CompAC will serve as a model for others in industry and government to follow in addressing this crucial issue of improving the process of expanded access.

I believe patients—who have been integral to the development of thousands of drugs over the years— deserve a dedicated, simplified process to help those who do not qualify for clinical trials. Additionally, we must also increasingly focus on biomarker-driven studies, which might offer options to patients who do not otherwise qualify for trials, frequently due to having received too many prior lines of therapy.

The mere fact that we are finally openly discussing this issue is progress in itself. This is also definitely the product of the tremendous advancement in oncology— the fact that we have had great success in developing novel agents has been game-changing and means that, logically, we as a society must now make the best effort to help patients with refractory disease benefit from this progress. It is a wonderful problem to have—let’s address it!