073 | Digitalizing clinical trials, dangerous vaccines and hope for HIV

Happy 2018 from Biotechnology Focus! Ahead on today’s episode are some of the headlines that are shaking things up in the new year.   Sanofi launches digital clinical trials for increased probability of participation  A repurposed drug could be the key to successful stem cell transplants  Experts advise caution of the use of Sanofi’s dengue vaccine as new warnings are added to the label  Virus vs. Virus – could Maraba knock out HIV?  Welcome to another episode of Biotechnology Focus radio. I am your host, Michelle Currie, here to give you a run-down of the top stories of Canada’s biotech scene.  +++++  First up this week, Sanofi launches a digital way to partake in clinical trials – to make participation more widely available and lower the duration of the trial itself. Clinical trials are a crucial step to putting the potentially life-saving medication on to shelves. However, due to the specifics required for each participant and their proximity to a research centre, 80 per cent of clinical trials are delayed due to recruitment problems in the US alone according to a study by the Centre of Information and Study on Clinical Research Participation (CISCRP).  Unfortunately, these delays prevent some of these innovative medicines from reaching its patient base or taking longer than necessary. Sanofi, partnering with Science 37 decided to tackle this problem head-on by taking a digital approach.  According to the study by Centre of Information and Study on Clinical Research Participation, 87 per cent of patients are willing participants for clinical studies, but yet 70 per cent of them live over two hours away from a research centre – deterring them. Many studies require the participant to check in a few times a week, which is too far for most people to attend during their busy lives.  Science 37’s approach allows patients to be monitored and report to researchers via an Apple iPhone equipped with the company’s NORA technology. Qualified study participants are provided with the phone, a data plan, any sensors or any devices needed to obtain the information for the study. With quick access to researchers, mobile nurses and under the care of local health care professionals, this could be a solution the geographical gap.  Sanofi’s agreement with Science 37 covers use of its Metasite model and NORA technology across the U.S. with plans to expand internationally in the future. By eliminating months of searching for patients and long travel time to study sites, virtual clinical trials could reduce total trial time by as much as two years.  +++++  Canada is known for its long track record of success in stem cells, specifically in blood stem cells, and the research from British Columbia will be no exception. Peter Zandstra, a founder and chief scientific officer at the Centre for Commercialization of Regenerative Medicine (CCRM) and director of UBC’s new School of Biomedical Engineering, as well as researchers from UofT and UBC, publish in Science Translation Medicine, a potential way to repurpose an anti-inflammatory drug for blood stem cell transplants.  Earlier work looked at cell interaction and signaling between cell population where the researchers noticed that one of the growth factors tumour-necrosis-factor-alpha (TNF-a) – a protein that cells deploy against infection, which is sometimes overproduced, killing healthy cells – had a negative effect on blood stem cells. This observation emerged when the researchers did not get the expected number of stem cells to rise to mature blood cells during blood stem cell transplantation. This finding influenced Zandstra to explore whether one of several existing drugs that block TNF-a would allow human blood cells to thrive in a new host.  Zandstra and his team added the blocking agent either with the transplant or up to two weeks later. The results they received from testing on animal models far surpassed expectations. The mice had numerous more blood stem cells, and more importantly, diversification – more rapid T and white blood cells, which suggested a healthy transplant.  Zandstra had stated that this could lead to using smaller grafts, and would provide two main benefits. The first being that there are many of those available with a large pool from which to choose; and second, the potential to have better matches from those existing pools. A significant portion of banked umbilical cord blood is simply not suitable for use on adults because they are either too small or not appropriately matched.  These results provide a strong basis to advance the research to clinical trial and observe whether TNF-a blockers improve patient outcomes or save lives. This repurposed drug could be the key to successful stem cell transplants.    +++++  If you’re thinking about going on holiday this winter season and deciding which vaccines to get for your trip – experts at World Health Organization are advising caution of the use of Sanofi’s dengue vaccine, at least for now. The vaccine, could be putting people, especially children, at a heightened risk of severe disease.    Sanofi recently changed the warnings on the label of their vaccine, Dengvaxia, even though experts from the World Health Organization (WHO) had told them a year previously that the vaccine had safety risks and should only be used in people who have had a previous dengue infection.  Based on six-years of clinical data, the analysis from Sanofi that evaluated the long-term safety and efficacy of Dengvaxia in people who had been infected with dengue previously and with those who had not, confirmed that it should only be used in people who had a previous infection and over the age of 9 in dengue-infested regions. The age recommendation coming from surveillance data which indicated that 70-90 per cent of people will have been exposed to dengue by the time they reach adolescence.  Dengue, a mosquito-borne viral disease is painful and debilitating, for which there is no treatment. Approximately 4 billion people are at risk of dengue fever. It hits hardest in rainy seasons around tropical areas and can be lethal. There are five strains of the virus, but only one will provide the infected with anti-bodies for lifelong immunity. The other strains will, unfortunately, have a short-term immunity, leaving the infected with the potential of subsequent infections that can cause severe complications.  The vaccine, which can act as a first infection to those who have not been infected with dengue before, has been approved in 19 countries and launched in 11. The Philippines, who had invested a hefty sum into the dengue vaccination program recently pulled the vaccine off the shelves after Sanofi’s statement that the vaccine could cause “severe disease” was released. The country braces for the worst after hearing this news and after the immunization of over 730,000 children.  Sanofi urges physicians and health authorities to update the information regarding the vaccine.  +++++  Researchers at the University of Ottawa and the Ottawa Hospital discover that the Maraba virus, or MG1, is effectively targeting and destroying the kind of HIV-infected cells that standard antiretroviral therapies can not reach. These findings were published in the Journal of Infectious Diseases and may very well help lead to a cure for HIV in humans.  While there are certain “cocktails” that are taken daily by people who have been diagnosed with HIV, there is no current cure for the disease, even when the cells lie dormant and a person is deemed “undetectable”. “Undetectable” meaning that they are undergoing antiretroviral therapy and their white blood cell counts have increased and their viral load significantly decreased to an “undetectable” level – but there it lies in wait – for the virus load will quickly rebound if one of these “cocktails” are missed.  These latent HIV-infected cells are hard to target because they are not distinguishable from normal cells. Dr. Jonathan Angel’s team had decided to try an innovative approach to identifying these dormant cells using the MG1 virus. This virus attacks cancer cells that have defects in their interferon pathway, which makes the cells more vulnerable to viruses. Previously, Angel and his team had discovered that latent HIV-infected cells shared this defect.  The research group used several laboratory models of latent HIV-infected cells to discover that the MG1 virus targeted and eliminated the HIV-infected cells and left the healthy cells unharmed.  While most of these cells in patients are in the lymph nodes and other organs, a tiny number are found in the blood. When the researchers added MG1 to relevant blood cells taken from HIV-positive individuals, the levels of HIV DNA in the sample dropped. This indicated that the HIV-infected cells had been eliminated.  Pending funding and approvals, the research team’s next step is to try the virus in animal models of HIV or move directly to clinical trials. Further examination and time will tell whether this is a knockout solution for combating HIV.  +++++  Canada is known for its long track record of success in stem cells, specifically in blood stem cells, and the research from British Columbia will be no exception. Peter Zandstra, a founder and chief scientific officer at the Centre for Commercialization of Regenerative Medicine (CCRM) and director of UBC’s new School of Biomedical Engineering, as well as researchers from UofT and UBC, publish in Science Translation Medicine, a potential way to repurpose an anti-inflammatory drug for blood stem cell transplants.  Earlier work looked at cell interaction and signaling between cell population where the researchers noticed that one of the growth factors tumour-necrosis-factor-alpha (TNF-a) – a protein that cells deploy against infection, which is sometimes overproduced, killing healthy cells – had a negative effect on blood stem cells. This observation emerged when the researchers did not get the expected number of stem cells to rise to mature blood cells during blood stem cell transplantation. This finding influenced Zandstra to explore whether one of several existing drugs that block TNF-a would allow human blood cells to thrive in a new host.  Zandstra and his team added the blocking agent either with the transplant or up to two weeks later. The results they received from testing on animal models far surpassed expectations. The mice had numerous more blood stem cells, and more importantly, diversification – more rapid T and white blood cells, which suggested a healthy transplant.  Zandstra had stated that this could lead to using smaller grafts, and would provide two main benefits. The first being that there are many of those available with a large pool from which to choose; and second, the potential to have better matches from those existing pools. A significant portion of banked umbilical cord blood is simply not suitable for use on adults because they are either too small or not appropriately matched.  These results provide a strong basis to advance the research to clinical trial and observe whether TNF-a blockers improve patient outcomes or save lives. This repurposed drug could be the key to successful stem cell transplants.  +++++  Well that wraps up another episode of Biotechnology Focus. For the full stories, please visit the website biotechnologyfocus.ca. From my desk to yours – this is Michelle Currie.