One of the things I love about Cure HHT is the focus on research and clinical trials for patients. I’d like to use this post to talk about the Avastin clinical trial, which I recently saw posted on Cure HHT’s media pages.
Before delving into the background on this drug and its potential benefits to HHT patients, let me put out a disclaimer. Please talk with your physician if you think you may benefit from participating in a clinical trial. I am not a physician, nor am I a practicing medical professional. I am a scientific researcher and this post serves the purpose to summarize information about Avastin and its potential uses for the HHT community.
If you search for bevacizumab, or its brand name, Avastin, you’ll see it’s an FDA approved drug given to cancer patients to help minimize tumor growth. Your first thoughts may be ‘I don’t have cancer. Why should I try to take a cancer drug to stop my nose bleeds? Cancer drugs are harsh and scary!’
Bevacizumab is something called a monoclonal antibody, meaning it will bind to a specific target. Its target is vascular endothelial growth factor, or VEGF. In cancer, tumors secrete a lot of VEGF and it helps grow blood vessels, and therefore helps grow and spread the tumor. Bevacizumab binds to VEGF and tries to stop blood vessel formation.
About 10 years ago, a couple case studies were published after HHT patients treated for cancer with bevacizumab saw dramatic improvements in the frequency and severity of nosebleeds and hepatic bleeding (Bose, Holter, & Selby, 2009; Flieger, Hainke, & Fischbach, 2006). These patients received the drug through an IV at a high dose to treat their cancer, but the unexpected benefits to HHT symptoms sparked interest in the drug as a therapy for epistaxis.
There are a lot of drugs that have had intended uses, but researchers saw positive effects on an unrelated symptom and changed the drug’s intention. Viagra, for example, was developed as a drug to treat high blood pressure and chest pain, as it dilates blood vessels. However, blood vessel dilation in other areas were a happy side effect and now the drug has a different use!
This is one of the many reasons why clinical trials are so important. Not only can a well-developed research study pinpoint good side effects, it can also pinpoint negative ones as well.
With science, nothing is ever simple and there are always a lot of caveats. It would be great if this drug could be given in an IV and nosebleeds would get better, right? The tricky part is VEGF is something we need to be healthy, so if we try to disable it throughout our entire body, there could be other serious complications.
Researchers have tried administering the drug in a lower dose IV as well as with nasal spray, topical ointment and a submucosal injection. All have been shown to improve nosebleeds in patients with HHT, and since the dose of Avastin is so low there were no negative side effects.
Case closed, right? Well, these research studies did not directly compare its effects to a control, they did not have very many patients and some were merely case studies of a single patient (Simonds, Miller, Mandel, & Davidson, 2009; Suppressa, Liso, & Sabba, 2011; Thompson et al., 2014).
This does not mean these research studies should be discredited. They are all important pieces of information along the journey to see bevacizumab used as a treatment for HHT.
These studies and their findings led to the initiation of a clinical trial across six HHT centers of excellence comparing bevacizumab with a placebo and two other drugs in the North American Study on Epistaxis (NOSE) (Whitehead et al., 2016). In this study, patients either received a saline spray (the control for the study) or one of three drugs to spray in their nose twice a day.
The study concluded and found there were no differences between the four groups of patients receiving the different medicines or placebo. The study lists a couple of important limitations: 1) they did not have patients keep a diary of nosebleeds before the study started, so there was no way to quantitatively compare patients before and after treatment and 2) they were not sure how effective the drug delivery was because the nose can be pretty crusty in HHT patients due to dried blood that may block the medicine’s entry.
After all this (and much more past research), a phase IV clinical trial is now ongoing to study bevacizumab injection in the nose right after electrocautery treatment. All patients will receive electrocautery treatment, half will get an injection of bevacizumab and the other half will receive a placebo. This should ideally enhance the drug’s effects, as the nose will be cleaned of debris, cauterized and injected with the medicine.
Researchers at Stanford need several more volunteers in order to help complete this clinical trial. If you have talked with your physician, met the eligibility criteria for the study found here and are interested in helping advance the science behind this drug, I encourage you to contact the study team! If you were on the fence about participating in this trial, I hope the interesting background of Avastin has helped you make a decision!
Bose, P., Holter, J. L., & Selby, G. B. (2009). Bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med, 360(20), 2143-2144. doi: 10.1056/NEJMc0901421
Flieger, D., Hainke, S., & Fischbach, W. (2006). Dramatic improvement in hereditary hemorrhagic telangiectasia after treatment with the vascular endothelial growth factor (VEGF) antagonist bevacizumab. Ann Hematol, 85(9), 631-632. doi: 10.1007/s00277-006-0147-8
Simonds, J., Miller, F., Mandel, J., & Davidson, T. M. (2009). The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope, 119(5), 988-992. doi: 10.1002/lary.20159
Suppressa, P., Liso, A., & Sabba, C. (2011). Low dose intravenous bevacizumab for the treatment of anaemia in hereditary haemorrhagic telangiectasia. Br J Haematol, 152(4), 365. doi: 10.1111/j.1365-2141.2010.08481.x
Thompson, A. B., Ross, D. A., Berard, P., Figueroa-Bodine, J., Livada, N., & Richer, S. L. (2014). Very low dose bevacizumab for the treatment of epistaxis in patients with hereditary hemorrhagic telangiectasia. Allergy Rhinol (Providence), 5(2), 91-95. doi: 10.2500/ar.2014.5.0091
Whitehead, K. J., Sautter, N. B., McWilliams, J. P., Chakinala, M. M., Merlo, C. A., Johnson, M. H., . . . Gossage, J. R. (2016). Effect of Topical Intranasal Therapy on Epistaxis Frequency in Patients
With Hereditary Hemorrhagic Telangiectasia: A Randomized Clinical Trial. JAMA, 316(9), 943-951. doi: 10.1001/jama.2016.11724