Drug Therapy for Lymphedema Starts Clinical Trials
A new drug intended to cure breast cancer related secondary lymphedema by restoring the damage to the lymphatic system damage caused by lymph node removal during cancer treatment (axillary lymph node dissection) has entered clinical trials in Europe.
Lymfactin is intended to improve growth of new lymphatic vessels and restore lymphatic system function by using adenovirus-based gene therapy to increase levels of biological signal VEGF-C, a growth factor that is specific to the lymphatic system. A single dose of Lymfactin is administered during a surgical operation where the patient’s own lymph node tissue is transferred into the damaged area (autologous lymph node transfer).
Herantis has launched a phase I clinical study at three European clinical sites. While the primary endpoint of the study is to assess the safety and tolerability of Lymfactin the study will also assess the preliminary efficacy of the treatment. The first site opened for patient recruitment in May 2016 is Helsinki University Central Hospital. Two further study sites in Finland are planned for later this year. The study intends to recruit at most 18 patients with breast cancer related lymphedema.
Preclinical studies in animal models of breast cancer related lymphedema have confirmed that Lymfactin promotes growth of new lymphatic vessels and functional improvement of lymphatic flow. Lymfactin is based on the academic research of Professor Kari Alitalo and his research group at the University of Helsinki.
Drug development can take 10–15 years starting with preclinical studies, followed by three phases of the clinical stage, and market approval. This drug has completed the preclinical stage and entered the clinical stage involving human subjects. The current Phase 1 clinical study assesses the safety of a drug candidate in human subjects. In Phase 2, the optimal dosing and possible efficacy in the treatment of a particular disease is studied. Phase 3 studies aim to establish a statistical proof of safety and efficacy for market approval and may require hundreds or thousands of patients.
VEGF, or vascular endothelial growth factor, is a biological signal that influences growth of the blood and lymphatic vascular system. VEGF also supports many physiological functions including bone formation, wound healing, and development.
There are six types of VEGF signals (VEGF-A to VEGF-D and placental growth factor (PGF)) and three different types of VEGF receptors (VEGFR-1 to VEGFR-3). Each type of VEGF signal supports different functions. Lymfactin targets VEGF-C, the signal associated with healthy lymphatic growth.
Abnormal VEGF-A signals are produced by tumor cells to create a blood supply for tumors by growing new blood vessels and to enable tumors to spread (metastasize) via abnormal lymphatic vessels. VEGF-A levels are also elevated in people with rheumatoid arthritis, diabetes, and other conditions. Anti-angiogenic drugs and foods fight cancer and other diseases target by countering abnormal VEGF-A signaling. See Chapter 2 of the Lymphedema and Lipedema Nutrition Guide (Lymph Notes 2016).
References
- Herantis product description: http://herantis.com/pipeline/lymfactin-for-lymphedema/
- Heranatis press release: http://herantis.com/release/finnish-medicines-agency-authorization-of-first-in-man-clinical-study-with-lymfactin/
- Herantis press release: http://herantis.com/release/herantis-pharma-initiates-patient-recruitment-for-clinical-study-with-lymfactin-in-breast-cancer-associated-lymphedema/
- Visuri MT, et al. VEGF-C and VEGF-C156S in the pro-lymphangiogenic growth factor therapy of lymphedema: a large animal study. Angiogenesis. 2015 Jul;18(3):313–26. http://www.ncbi.nlm.nih.gov/pubmed/26018927
- Tervala TV, et al. Growth factor therapy and lymph node graft for lymphedema. J Surg Res. 2015 Jun 1;196(1):200–7. doi: 10.1016/j.jss.2015.02.031. Epub 2015 Feb 19. http://www.ncbi.nlm.nih.gov/pubmed/25777822
