A Phase II Study Done at Northwestern Hospital Shows Potential Relief for Diabetics with Painful Condition
Northwestern Memorial Hospital (Northwestern University's Feinberg School of Medicine) announced the results from a new phase II clinical study published in the journal Annals of Clinical and Translational Neurology on March 5th. The study, “Double-blind, Placebo-controlled Study of HGF Gene Therapy in Diabetic Neuropathy”, reviewed the results of the study from the US and Korea involving 103 painful diabetic neuropathy (PDN) patients from 17 hospitals.
According to the report, patients who received low dose (16 mg) of the gene therapy drug VM202-DPN, developed by ViroMed (KOSDAQ:084990), experienced a significant pain reduction in 3 months and persisted up to 9 months. The most striking finding was that VM202 had much greater effects on patients not on conventional medicines. Patients who were not benefitting from current treatment options now have hope.
20 ~ 25% of diabetes patients suffer from the disease and feel intense pain with a slight graze or touch due to damaged nerve cells, but no treatments are available yet. Painkillers such as Lyrica and Cymbalta are used to only temporarily alleviate the pain, but these drugs are well known for the intolerable side effects. It is reported that because of the not-so-trivial side effects and/or the inconvenience associated with taking the drug daily, 60 ~ 70% of DPN patients do not or cannot take these drugs (Nature Reviews Drug Discovery, 2012(11)).
Results from this clinical study show that VM202-DPN, with only 2 treatments with 2 weeks interval, can induce high level of pain reduction for 3 - 9 months. As the results show signs of recovery of damaged neurons with almost no adverse effects associated with the drug, VM202-DPN is considered to become a very safe and effective drug. For these reasons, if the drug enters the market after phase III, it may transform the current PDN market.
Dr. Senda Ajroud-Driss, associate professor in neurology at Feinberg, an attending physician at Northwestern Memorial Hospital and an author of the study said “We are hoping this therapy increases the production of the growth factor to help treat the pain and help grow blood vessels, with little or no side effects” to emphasize the need for drugs like VM202.
According to ViroMed, the published paper reports that VM202 had no drug related adverse effects and VM202 administered group had significantly better results compared to the placebo group. Pain reduction level and rate of patients who experience 50 % or more pain reduction (50% responder rate) are some of the important measurements for efficacy.
It is commonly acknowledged that when the pain level decreases by more than 1, it is considered clinically meaningful. In the Daily Pain Diary, which measures the changes in pain over 24 hour period, the differences in pain level between baseline and 3 months after injection were 1.5 for placebo group, 3.0 for VM202 16 mg group, and 1.9 for VM202 32 mg group. When compared to the placebo group, VM202 16 mg group showed increased pain level reduction of 1.5.
Also, while only 17.6 % of patients in the placebo group showed 50 % or more pain reduction, 48.4 % of patients in the VM202 16 mg group showed 50 % or more pain reduction. The difference in percentage between the two groups is 30.8 %, which is higher difference than that of Lyrica1).
1)Lyrica: Percentage of patients experiencing 50% or more pain reduction
- Placebo: 14.5%, Lyrica 300 mg: 40%, difference of 25.5%. Neurology, 2004, Lesser H, et al.,
One of the most important outcomes of this clinical study was that the percentage of patients showing 50 % or more pain reduction in VM202 treated groups increased significantly when only taking into accounts the patients who were not taking Lyrica or Neurontin. For patients not taking Lyrica or Neurontin in the VM202 16 mg group, the pain level was reduced by 3.6 with 68.4 % of patients showing 50 % or more pain reduction 3 months after injection. This shows that VM202 has an excellent pain reduction effect without the use of commonly prescribed drug treatments and could possibly expand the current market.
“I can now go to a beach and walk on the sand without feeling like I am walking on glass,” said Keith Wenckowski, one of the patients who participated in the study.
“Those who received the therapy reported more than a 50 % reduction in their symptoms and virtually no side effects,” said Dr. Jack Kessler, lead author of the study. “Not only did it improve their pain, it also improved their ability to perceive a very, very light touch. Right now there is no medication that can reverse neuropathy. Our goal is to develop a treatment."
Dr. Kessler is the Ken and Ruth Davee Professor of Stem Cell Biology in the department of neurology and a professor in the department of pharmacology at Northwestern University Feinberg School of Medicine. He also is an attending physician at Northwestern Memorial Hospital.
About Diabetic Peripheral Neuropathy
DPN is a neuronal disorder caused by abnormally high level of glucose in diabetes patients, mostly occurring in lower limbs. The high level of glucose can be toxic and damages microvasculature of the diabetes patients, which in turn damages nerve cells due to lack of supply of nutrients to these cells. These damaged nerve cells send out abnormal signals, causing the patients to feel abnormal pains that progresses with the disease. Patients with painful DPN, the most extreme form of the disease, feel extreme pain with a slight graze or touch. There are currently no fundamental treatments for the disease and maintaining glucose level in blood through strict diet is the only known method to diminish the disease incidence. Pain killers such as Lyrica and Neurontin are prescribed as an adjuvant therapy to help patients cope with pain, but are only symptomatic treatments and are not effective for all patients. The disease occurs in 5 ~ 20 % of diabetes patients (worldwide: 387 million, US: 26 million). When VM202 is intramuscularly injected into these patients, it produces HGF protein that is both neurotrophic factor and can induce angiogenesis (formation of new blood vessels). HGF proteins than induce formation of microvasculature and regenerate nerve cells to treat the disease.
VM202-DPN is part of a group of therapeutics derived from VM202. VM202-DPN is a DNA based drug that can create microvasculature and regenerate nerve cells. When VM202-DPN is injected into patients it produces what is called hepatocyte growth factor (HGF) protein that induces angiogenesis and acts as a neurotrophic factor, which leads to formation of new microvasculature and regenerate nerve cells. The results from Phase I clinical study already showed the possibility of VM202-DPN as a new concept drug and the results have already been published (Molecular Therapy 2013, 21: 1279–1286). It is expected that VM202-DPN will ultimately become the new drug that not only fundamentally treats the disease, but also improves pains in DPN patients.
The study was sponsored by ViroMed Co., Ltd. dba VM BioPharma; an R&D focused Biopharmaceutical Company located in Seoul, Korea. ViroMed is developing new and innovative biopharmaceuticals for the treatment of currently untreatable diseases. VM202 has been developed by ViroMed using proprietary vector system and genetically modified HGF gene.