Today's post from the always excellent sciencedaily.com (see link below) is another article about VM202 - (that unattractively-named, new non-viral gene therapy we've mentioned a couple of times in the last 2 weeks). The difference here is that it is relatively easy for the casual reader to understand and certainly seems to be something to start becoming cautiously excited about. Remember too, that just because the title includes the word 'diabetics' doesn't mean that it doesn't apply to most other forms of neuropathy too.
Neuropathy: Relief for diabetics with painful condition
Date:March 5, 2015 Source: Northwestern University
Summary:
Those with painful diabetic neuropathy who received two low dose rounds of a non-viral gene therapy called VM202 had significant improvement of their pain that lasted for months, researchers report. "Right now there is no medication that can reverse neuropathy," the study's first author said. "Our goal is to develop a treatment. If we can show with more patients that this is a very real phenomenon, then we can show we have not only improved the symptoms of the disease, namely the pain, but we have actually improved function."
Walking barefoot on sand "felt like walking on glass" for Keith Wenckowski, who has lived with type-one diabetes for more than two decades.
One of the participants in a new Northwestern Medicine study who suffered from painful diabetic neuropathy (PDN), Wenckowski finally found relief from the constant foot pain that required him to wear shoes at all times, even to the beach.
The study found that those with PDN who received two low dose rounds of a non-viral gene therapy called VM202 had significant improvement of their pain that lasted for months.
"I can now go to a beach and walk on the sand without feeling like I am walking on glass," Wenckowski said.
The results of this phase two, double-blind, placebo-controlled study will be published March 5 in the journal Annals of Clinical and Translation Neurology.
Right now there is no treatment for this disease of the peripheral nerves that affects 20 to 25 percent of diabetics. Patients with the most extreme form of the disease feel intense pain with a slight graze or touch. The pain can interfere with daily activities, sleep, mood and can diminish quality of life.
"Those who received the therapy reported more than a 50 percent 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."
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.
VM202 contains human hepatocyte growth factor (HGF) gene. Growth factor is a naturally occurring protein in the body that acts on cells -- in this case nerve cells -- to keep them alive, healthy and functioning. Future study is needed to investigate if the therapy can actually regenerate damaged nerves, reversing the neuropathy.
Wenckowski had continuous numbness, but now, more than a year since he received the therapy, his symptoms have not returned. "I am hoping the effects I am feeling do not cease," he said.
Patients with painful diabetic neuropathy have abnormally high levels of glucose in their blood. These high levels of glucose can be toxic.
Damaged nerve cells send out abnormal signals, causing the patients to feel pain, usually in their lower limbs and fingertips. The condition can lead to injuries, chronic foot ulcers and even amputations.
Painkillers and other medications can alleviate symptoms, but those drugs often come with undesirable side effects.
"We are hoping that the treatment will increase the local production of hepatocyte growth factor to help regenerate nerves and grow new blood vessels and therefore reduce the pain," said Dr. Senda Ajroud-Driss, associate professor in neurology at Feinberg, an attending physician at Northwestern Memorial Hospital and an author of the study.
Eighty-four subjects with PDN completed this study. They went to a clinic twice in a two-week timespan for a series of injections into the back of their calf muscles and lower legs. Some received injections of a saline placebo, others a low dose of the therapy and others a higher dose.
"We found that the patients who received the low dose had a better reduction in pain than the people who received the high dose or the placebo," Ajroud-Driss said. "Side effects were limited to injection site reaction."
The subjects reported their pain symptoms to the researchers over the next nine months. At three months, patients in the low-dose group experienced a significant reduction in pain compared to the placebo group. The effect persisted at six and nine months in the low-dose group, the scientists said.
A future, much larger phase three study will soon be underway.
"Right now there is no medication that can reverse neuropathy," Kessler said. "Our goal is to develop a treatment. If we can show with more patients that this is a very real phenomenon, then we can show we have not only improved the symptoms of the disease, namely the pain, but we have actually improved function."
Story Source:
The above story is based on materials provided by Northwestern University. Note: Materials may be edited for content and length.
Journal Reference:
John A. Kessler, A. Gordon Smith, Bong-Soo Cha, Sung Hee Choi, James Wymer, Aziz Shaibani, Senda Ajroud-Driss. Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy. Annals of Clinical and Translational Neurology, 2015; DOI: 10.1002/acn3.186
http://www.sciencedaily.com/releases/2015/03/150305110534.htm
A new development in DNA medication for neuropathy is on the way. This article from 4-traders.com (see link below) tells that the Korean FDA has approved trials of VM202-DPN, which has shown extremely promising results in preliminary testing. Only two injections given over two weeks, produced long-lasting relief from pain. Approval from the American FDA is the bench mark generally for the rest of the world but it looks good so far. Hopefully by the time ViroMed get it on the market, it will have a more customer friendly name! 
Approval from the Korea FDA for a Phase II clinical trial for diabetic peripheral neuropathy
04/13/2012 |
Its great potential has already been shown by the groundbreaking results from the Phase I/II clinical trial conducted in the US which confirmed the safety as well as the efficacy of VM202-DPN. Only two injections (at 2-week intervals) produced prolonging pain-reduction effects which were still lasting by the end of the 1-year follow-up period. ViroMed received approval for Phase II trial last year in the US based on these exciting and promising Phase I/II results. John A. Kessler, MD., of Northwestern Memorial Hospital, Chicago, US, will be the principal PI of this multinational Phase II study, and a total of 100 patients will be enrolled to evaluate the efficacy of VM202-DPN. About 7 hospitals in the US including Northwestern Memorial Hospital, Beth Israel Deacons Medical Center (Harvard Univ.), and the Mount Sinai Hospital, and 4-5 hospitals in Korea including Yonsei Univ. Severance Hospital will be participating for this study.
"This is an exceptional case among Korea's new drug development biotech companies." commented Jong-Mook Kim, the Director of Clinical Development Department of ViroMed. "Pre-existing drugs are only effective for temporary pain-relief and not without serious side-effects. With VM202-DPN's disease-modifying capabilities which would enable us to provide the fundamental cure for DPN patients, VM202-DPN will set a new trend in the current analgesic-driven diabetic neuropathy market."
According to the UK consulting firm Pelham Smithers Associates, the sales of existing medicines currently used to treat diabetic neuropathy were $1.5 billion in 2009. Since these drugs are symptomatic treatments which can only alleviate symptoms temporarily but cannot cure the underlying disease, it is expected that their market will not grow to over $2 billion. On the other hand, it is forecast that the global launching of disease-modifying drugs like VM202-DPN (estimated launching year: 2016) will drive the explosive growth of the market, expanding to be over $3 billion in 2020, and reaching $12 billion in 2025.
About VM202-DPN
VM202-DPN is ViroMed's proprietary DNA medicine using Hepatocyte Growth Factor (HGF), a gene that stimulates the growth of arteries. Recent experiments have shown that HGF also stimulates the growth and recreation of nerve cells, which raises exciting possibilities as a therapeutic for diabetic peripheral neuropathy. VM202-DPN has also been designed to have minimal side effects and to safely disappear from the body after its intended therapeutic effect has been produced.
Diabetic Peripheral Neuropathy market
There are approximately 285 million diabetes patients around the world, 50% of whom are also suffering from diabetic peripheral neuropathy (DPN) as a complication of diabetes. The number of DPN patients reaches 3.9 million in the US alone. (Diabetes Research and Clinical Practice, 2010)
According to Pelham Smithers Associates, an UK consulting firm specialized in data analysis, the sales of existing medicines currently used to treat diabetic neuropathy were $15 billion in 2009. After disease-modifying drugs like VM202-DPN are out to the global market (estimated launching year: 2016), it is forecast that the size of the market will be $2.5 billion in 2017, and grow to $5 billion in 2020.
Competitiveness of VM202-DPN
Existing drugs prescribed for the treatment of DPN are mostly pain killers, and the most-often-used of all is Pfizer's own "Lyrica" (worldwide sales of $1 bil/yr), a drug originally developed as epilepsy treatment. However, as "Lyrica" is the drug that temporarily relieves pain by blocking neurotransmitters, it must be used at twice-a-day basis for decades, and it is reported to produce nervous system-related side effects such as headache, insomnia and depression. Consequently, there have been high demands for safe and effective novel medicine for DPN as there are no fundamental treatments for it. To attend to those unmet needs, VM202-DPN is designed to treat the underlying disease by producing hepatocyte growth factor (HGF) that induces repair of damaged nerve cells and generation of micro-vessels in the affected regions of human body. Its great potential has already been shown by the resulting data from the Phase I/II clinical trial conducted in the US. It is reported that there were only 35% of the patients who experienced 50% or more reduction in pain level during clinical studies for "Lyrica"; however, 65% of the VM202-DPN treated patients experienced pain reduction only after two injections at 2-week intervals.
About ViroMed
ViroMed Co., Ltd. is a leading biotechnology company located in Seoul, Korea with a US presence in Atlanta and the San Francisco Bay Area. The company has two main areas of focus: DNA/protein-based biopharmaceuticals and phytotherapeutics (botanical drugs/nutraceuticals). ViroMed now has five main products in its pipeline targeting cardiovascular disease, cancer, and immune-related disorder, with clinical trials ongoing in the US, Korea, and China.www.viromed21.com.
http://www.4-traders.com/news/Approval-from-the-Korea-FDA-for-a-Phase-II-clinical-trial-for-diabetic-peripheral-neuropathy--14270738/
We've mentioned the subject of today's post from endocrinologyadvisor.com (see link below) several times already but this article explains this exciting new development in terms that almost everybody can understand. Certainly worth talking over with your doctor or specialist and maybe even getting your name onto some trial lists in your area (you may have to fight for that one). However, the idea of 8 injections per year taking away most of our pain, is a very attractive one - let's hope this is a development with real substance. Well worth a read.
Can Gene Therapy Reverse Diabetic Neuropathy?
John Schieszer, MA July 24, 2015 A nonviral gene therapy may relieve symptoms of painful diabetic neuropathy.
Gene therapy in the form of a plasmid containing two human hepatocyte growth factor isoforms administered via intramuscular injection may alleviate symptoms and improve quality of life in patients with painful diabetic neuropathy.
In addition, the plasmid —VM202 — may be particularly beneficial in those patients not taking gabapentin or pregabalin, according to researchers at Northwestern University.
In a recently completed double-blind, placebo-controlled study, 84 patients were randomly assigned to receive injections of 8 mg or 16 mg of VM202 per leg (calf muscles and lower leg) or placebo, with doses administered on days 0 and 14.
At 3 months, patients in the low-dose group experienced a significant reduction in pain compared with the placebo group, the researchers found.1
“I am very excited about it. This is an enormous problem, and it has a huge impact on people's lives. [These patients] spend so much time in agony,” said study investigator Jack Kessler, MD, who is a professor in the department of neurology at Northwestern University Feinberg School of Medicine in Chicago.
“The data are very, very strong. One issue that remains to be resolved is if we are modifying the disease, and at this time, the jury is still out. In our last study, we had some improvement in patients to feel light stimuli, but we need additional data to say we are altering the course of the disease. If our phase 3 study gives us the same results, then this treatment will be the best option for treating diabetic neuropathy.”
Study Results
The primary outcome for this current study was change in the mean pain score measured by a 7-day pain diary. The analysis also included quality of life and pain measures, and measurement of intraepidermal nerve fiber density, according to Kessler.
The study showed that patients receiving 8 mg of VM202 per leg improved the most in all efficacy measures, including a significant reduction at 3 months in the mean pain score. The reductions in pain continued but were not statistically significant at 6 and 9 months.
“We would probably inject patients four times a year. If it turns out that we are actually making the neuropathy better, then it is reason to think patients would graduate from this, but if it turns out we are just treating the symptoms and not the disease, then we would see injecting the patients four times a year,” Kessler said in an interview with Endocrinology Advisor.
The mean age of the patients in this study was 60 years (approximately 75% men), and the mean duration of diabetes was 15 to 16 years.
The researchers found that 48% of the patients experienced at least a 50% reduction in pain in the treated group compared with 17% in the placebo group. The study also demonstrated significant improvements in the brief pain inventory and the questionnaire portion of the Michigan Neuropathy Screening Instrument.
The researchers noted that the largest reductions in pain were found among patients not on pregabalin or gabapentin.
There were no significant adverse events attributable to VM202 and this treatment was deemed safe and well tolerated.
More to Learn
It is hoped that VM202, which contains a human hepatocyte growth factor gene, will increase the local production of hepatocyte growth factor to help regenerate nerves and grow new blood vessels and subsequently reduce the pain.
“We believe we are getting a two-for-one treatment. We are supplying nourishment to the nerves, but we are also helping to improve blood vessel function,” said Kessler. “The most remarkable thing is that we pushed the dose up and we had literally not one serious side effect in the entire trial, only [injection] site soreness.”
A large trial is now planned, and the researchers hope to enroll 475 patients at 20 sites across the United States starting in December.
Amanda Peltier, MD, who is an assistant professor of neurology at Vanderbilt University in Nashville, Tennessee, said these study findings are interesting, and this approach could represent a new way of treating diabetic neuropathy with fewer treatment-related adverse effects.
“There is a huge unmet need for diabetic neuropathy as the current medicines have side effects and do nothing to improve or retard the progression of the underlying neuropathy, only treat the pain. In addition, our understanding of diabetic neuropathy has improved for type 1 diabetes, but there has been little headway in improving neuropathy for patients with type 2 diabetes,” Peltier told Endocrinology Advisor.
Looking Ahead
According to M. Sue Kirkman, MD, who is a clinical professor of medicine and the medical director of the Diabetes Care Center Clinical Trials Unit at the University of North Carolina School of Medicine in Chapel Hill, this is a quality of life issue.
Although there are several medications that may help symptoms, they are not effective in all patients and may come with significant side effects, Kirkman said.
“This trial showed promising results, but was relatively small and short-term. Larger and longer-term trials will be important to see if the benefits pan out, and also to get a better feel for potential adverse events. Up to now, treatments for diabetic neuropathy have been purely palliative, with no interventions that seem capable of actually improving nerve function,” Kirkman told Endocrinology Advisor.
“There are some hints from this study that this agent could actually improve nerve function. If that pans out in larger trials, it would be very exciting, since lack of feeling in the feet from advanced diabetic neuropathy is a risk factor for foot ulcers and amputations.”
Reference
Kessler JA et al. Ann Clin Transl Neurol. 2015;2(5):465-478.
http://www.endocrinologyadvisor.com/diabetes/painful-diabetic-neuropathy-gene-therapy/article/428342/
