Part 1 of 2:
Patients Against Lymphoma: 2012 overview of new classes of drugs on the Critical Path to approval
and our role in research advocacy
An important part of our mission is to partner with researchers in the fight against lymphoma … such as, to provide patient perspectives on clinical trial design, raise awareness about trials, and to advance the routine and informed consideration of trials by patients and treating oncologists.
Fostering well-informed consent and awareness of trials also helps patients to understand the benefits and the limitations of standard therapies – helping patients to become more informed partners in their care.
We recognize that participation in a trial is not always appropriate and that enrolling in a study is a difficult decision that must be guided by trained physicians with first-hand information about the patient’s clinical circumstances.
… However, we believe that there are at least 7 clinical circumstances where participation in a trial can compare favorably to standard approaches.
What progress has been made in research
and what has been PAL’s role?
In short, many very promising new approaches to the treatment of lymphoma are emerging that will help us to manage lymphoma better and cure more patients – the classes of these drugs we list below.
PAL’s role in supporting clinical research is challenging to measure directly, due in part to privacy constraints. So we rely on feedback from the community and measuring how often our educational materials and tools are used (clicked).
2012 Website usage statistics for lymphomation.org:
Number of visits
See also About Our Trial Tools:
We also estimate our positive contribution to clinical research by the number of invitations to participate in the review of trial concepts and study by professional organizations (ASCO, AACR, SU2C, and the Alliance) and the National Cancer Institute.
Before stepping through the exciting new developments in clinical research, a little background is needed to appreciate what it takes to bring a new drug forward – and therefore what it will take to make good on new insights into the biology of the disease and also the host environment, notably the immune system.
The “Critical Path” – from bench-side to bedside and the role of patients
Clinical science is an ongoing building process. To use an analogy, each beam must be tested for safety and efficacy before being accepted as part of the structure – something secure for clinicians to prescribe for their patients and for science to build on.
Basic science has increased our understanding of the mechanisms or pathways that drive tumor growth and survival. The goal of clinical research is to design drugs that target disease pathways in order improve efficacy and reduce toxicity.
… Two example of “targeted drugs”: Rituxan, binding to cd20, AND the btk-inhibitor, which bind to part of the malignant cell that is overactive and causing sustained growth.
Clinical-phase testing begins with important basic questions: How much of the drug can you give the patient without causing bad effects? How long does the drug stay in the body? What signs of toxicity are seen in liver and kidney tests? Are other important organs affected … the heart, lungs, brain … and so on?
Fast-forwarding to phase-III tests, the ultimate questions: Do we live better or longer when using the new protocol compared to the standard of care? Almost any drug that has activity against a disease process will also have side effects. Do these bad effects offset the positives?
The FDA, the independent reviewers of clinical studies, has provided a whitepaper on the drug discovery and testing process – the path of a new drug from the lab to the clinic. This is called the “Critical Path.”
The timeline from basic discovery to approval of a new drug can be 5, 10, or 15 years. It is the clinical-phase of testing that takes the longest – about 7 years.
Unfortunately, some clinical trials never enroll enough patients and are terminated with the study question unanswered. So progress against lymphoma takes great science, but it also requires our participation. The scientists simply can’t make progress against lymphoma without our help!
Independent and rigorous review of clinical trial outcomes is an essential process that weeds out unsafe or ineffective new drugs, a process that takes about 6 months. Low referral in trials has many causes, but is largely a consequence of our fragmented and uncoordinated medical system.
Contrary to public perception it is the low referral rate by clinicians that delays and limits progress, not Regulatory Review.
Finally to an overview of the classes of new and approved drugs for lymphoma on the Critical Path:
- Antibodies – that bind to receptors on lymphoma cells
- Antibodies-drug conjugates – that deliver poisons to cancer cells via antibody
- Antibodies that are radio-labeled – delivering radiation to cancer cells via antibody (radio-immunotherapy)
- Cytotoxic therapy – that induce dividing cells to die by damaging the DNA
- Epigenetic therapy – that turn on or off genes that promote or suppress malignant behavior of the cells
- Kinase inhibitors – targeting aberrant (bad-acting) pathways in malignant cells
- Immune-modulating therapy – enhancing the number and activity of immune cells involved in antibody-induced immunotherapy.
- Immune-checkpoint-blockade – blocking the ability of tumor cells to evade or suppress the immune system
- Adoptive T-cell therapy – engineering t-cells to become an army programmed to kill tumor cells
Note: Here we provide a tool to help patients locate trials based on the type of agent
Thank you for your attention to the first installment of our 2012 report – and for your financial support that makes it possible.
See How to help
In the next installment we will give an overview of the progress that has been made in recent years based on new drug approvals and encouraging clinical outcome reports, along with very exciting recent discoveries.
President, Patients Against Lymphoma