Category Archives: Epidemiology

Bristol diabetes spin-out company acquired by Novo Nordisk

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The global healthcare company has acquired all of the shares of the Bristol supramolecular chemistry company, of which total payments under the agreement could ultimately exceed $800 million.

Novo Nordisk has acquired all of the shares of Ziylo, a University of Bristol spin-out company based at the Unit DX science incubator in Bristol, UK.

Ziylo has been pioneering the use of its platform technology – synthetic glucose binding molecules – for therapeutic and diagnostic applications.

The acquisition gives Novo Nordisk full rights to Ziylo’s glucose binding molecule platform to develop glucose responsive insulins.

The development of glucose responsive insulins is a key strategic area for Novo Nordisk in its effort to develop this next generation of insulin, which would lead to a safer and more effective insulin therapy.

A glucose responsive insulin would help eliminate the risk of hypoglycaemia, which is the main risk associated with insulin therapy and one of the main barriers for achieving optimal glucose control. Thus, a glucose responsive insulin could also lead to better metabolic control and overall reduce the burden of diabetes for people living with the disease.

Prior to closing of the acquisition, certain research activities have been spun out of Ziylo to a new company, Carbometrics. Carbometrics has entered into a research collaboration with Novo Nordisk to assist with ongoing optimisation of glucose binding molecules for use in glucose responsive insulins.

Carbometrics has licenced rights to develop non-therapeutic applications of glucose binding molecules, with a focus on developing continuous glucose monitoring applications.

Ziylo’s glucose binding molecules are synthetic molecules that were designed by Professor Anthony Davis at the University of Bristol. These stable, synthetic molecules exhibit an unprecedented selectivity to glucose in complex environments such as blood.

The combination of this technology with engineered insulin pioneered by Novo Nordisk aspires to realise the world’s first glucose responsive insulin and transform the treatment of diabetes.

“We believe the glucose binding molecules discovered by the Ziylo team together with Novo Nordisk world-class insulin capabilities have the potential to lead to the development of glucose responsive insulins, which we hope can remove the risk of hypoglycaemia and ensure optimal glucose control for people with diabetes,” said Marcus Schindler, senior VP, Global Drug Discovery, Novo Nordisk.

“Novo Nordisk is the ideal company to maximise the potential of the Ziylo glucose binding molecules in glucose responsive insulins and diabetes applications, and it brings hope of a truly groundbreaking treatment to diabetes patients,” said Dr Harry Destecroix, CEO and cofounder of Ziylo.

Novo Nordisk has acquired all shares in Ziylo for an upfront payment and earn-outs with contingent milestone payments. Total payments under the agreement could ultimately exceed $800 million upon the achievement of certain development, regulatory and sales milestones by Novo Nordisk.

SOURCE: www.manufacturingchemist.com/news

Long-term prostate cancer prevention benefits of finasteride seen in insurance claims

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Men who take the medication finasteride get a prostate cancer prevention benefit that can last 16 years – twice as long as previously recorded, according to SWOG clinical trial analysis published in the Journal of the National Cancer Institute.

This finding was made possible by a new research strategy – linking Medicare claims data to clinical trial data, in this case from a landmark study run by SWOG, the federally funded cancer clinical trial network.

The SWOG study, known as the Prostate Cancer Prevention Trial, or PCPT, set out to see whether finasteride, a drug used to treat symptoms of prostate enlargement as well as male pattern baldness, would prevent prostate cancer in men over the age of 55.

The study enrolled 18,882 men from 1993-1997.

It was stopped in 2003 when investigators learned that finasteride reduced prostate cancer risk by 25 percent when compared with a placebo.

SWOG leader Ian Thompson, Jr., MD, of CHRISTUS Santa Rosa Hospital Health System, was the study chair of PCPT.

Joseph Unger, PhD, a SWOG biostatistician and health services researcher from Fred Hutchinson Cancer Research Center, has a track record of using new research methods to answer bigger, bolder questions about cancer prevention and treatment.

Along with SWOG colleague Dr. Dawn Hershman, Unger has pioneered for a decade the use of secondary sources of data, such as Medicare claims, U.S. Census Bureau data, and public health statistics from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program, to examine new hypotheses.

For this study, Unger wanted to know if the protective effects of finasteride lasted longer than seven years – the amount of follow-up evaluated in the PCPT.

Answering this question would typically require reopening the old study, reconnecting with patients, and conducting extensive follow-up – an expensive and time-consuming proposition.

But Unger took another tack, requesting and obtaining a data use agreement from the federal Centers for Medicare & Medicaid Services to access to records from Medicare, the health insurance program for people over 65.

Using patient information from the PCPT, Unger linked patients enrolled in the PCPT to their Medicare claims from 1999 through 2011.

The team was surprised to find they were able to successfully link 75 percent of PCPT trial participants.

Unger and colleagues at Fred Hutch created an algorithm to flag a prostate cancer diagnosis in the Medicare data, and examined the diagnoses over time.

The team identified 3,244 PCPT participants who were later diagnosed with prostate cancer over a median follow-up of 16 years, and found that participants on the PCPT that took finasteride had a 21 percent decreased risk of getting prostate cancer, compared to those who took a placebo drug, over the course of those 16 years.

“These findings raise the intriguing possibility that seven years of finasteride can reduce prostate cancer diagnoses over a much longer period than was previously shown,” Unger said. “It’s a low-cost generic drug, with minimal side effects, that can have a benefit that lasts long after men stop taking it.”

At the same time, Unger said, the SWOG study shows the value of using Medicare claims to extend follow-up for trial participants and answer new questions about cancer care and prevention.

“These secondary data sources are emerging as a new paradigm for long-term follow up for cancer clinical trials,” he said. “It’s an exciting new avenue of research.”

SOURCE: www.ecancer.org/news

Albendazole-antibiotic combination shortens therapy for parasitic diseases

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Researchers have found a way of reducing the treatment required for lymphatic filariasis and onchocerciasis from several weeks to seven days.

Researchers have found a way of significantly reducing the treatment required for lymphatic filariasis and onchocerciasis from several weeks to seven days.

By targeting Wolbachia, a bacterial symbiont that the filarial parasites need to live, the team has discovered a drug synergy that enables effective treatment over a shorter time.

Researchers provide proof-of-concept of a radical improvement to the targeting of Wolbachia via a drug synergy between the anthelmintic drug albendazole and antibiotics.

As part of the A*WOL programme, we have screened all registered drugs for anti-Wolbachia activity, which has allowed us to look at repurposing existing and registered drugs against these debilitating conditions.

The combination of an antibiotic and the anti-worm drug albendazole provided the greatest surprise when they acted synergistically to reduce the treatment time from weeks to days, opening up the opportunity to scale-up this approach at the community level” said Professor Mark Taylor from the Liverpool School of Tropical Medicine.

The team believe that their work is of immediate public health importance because the drugs that have been used, rifampicin and albendazole, are already registered. “These drugs can be tested in infected people as soon as possible,” continued Prof Taylor.

Dr Joe Turner, LSTM first author on the paper, added, “The discovery of drug synergy between a common anthelmintic and different classes of antibiotics is also exciting because even more, potent synergism may be evident when we combine with our next generation, ‘designer’ anti-Wolbachia drugs currently in development as part of the A*WOL programme. Potentially, we may be in a position to reduce curative treatment time frames down to five days or less for filariasis, with better acceptability and reduced costs for patients and local health systems”

What is Lymphatic filariasis?

Lymphatic filariasis (LF), which can cause elephantiasis or hydrocele, swelling of the limbs or scrotum and onchocerciasis, also known as river blindness affect millions of people in some of the world’s poorest communities. Both are caused by filarial parasites for which the bacterial symbiont Wolbachia is essential for development.

Filarial Neglected Tropical Diseases are prioritised for elimination, in line with fulfilment of the 2030 United Nations Sustainable Development Goals. A consensus of expert opinion, including the WHO, and major donors, USAID and UK DFID, considers that successful implementation of a macrofilaricidal or permanent sterilising drug would greatly accelerate the endgame elimination of lymphatic filariasis and onchocerciasis.

Traditional treatment for these conditions require repetitive, long-term mass drug administrations, and although targeting the symbiont with doxycycline has proved clinically effective, it is programmatically challenging due to the long treatment time and exclusion of pregnant women and children.

SOURCE: www.europeanpharmaceuticalreview.com/news/68466

Epidemic preparedness: Protecting the world from the next infectious disease

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Dr Richard Hatchett, CEO of the Coalition for Epidemic Preparedness, details the lessons learned from the Ebola outbreak and the urgent need to equip the world to face future epidemics.

How did CEPI come about?

CEPI was formally established at Davos 2017 in January, and initially with funding close to $500 million, provided by five major investors. The original investors were the Wellcome Trust and the Bill & Melina Gates Foundation, and three sovereign investors: Germany, Norway and Japan. We also received the extensive support of the World Economic Forum and the government of India as additional founding partners.

About a year’s worth of prior planning had gone into setting CEPI up; the day that it was formally established, we also issued our first call for proposals to develop vaccines against three high-priority pathogens – Mers, Lassa and Nipah. These pathogens have been identified by WHO on a shortlist that was published as part of their R&D blueprint, as part of their action against epidemic diseases.

CEPI has had a tremendously active year – we’re still very much in our initiation stage. I came on board as CEO in the middle of April and the major activities have been centred around building the organisation, developing a more structured internal organisation chart. When I was appointed at the February board meeting, the initial charge to me was to come back with some revisions to CEPI’s governance, which was specifically and explicitly an interim government structure designed for the initiation stage. The board recognised that the needs of the organisation would evolve over time and so they asked me to come back with recommendations as we move towards a steady-state phase.

How did the collaboration with sovereign investors arise and how many more countries do you hope to get on board?

Currently, the original investors all have well-established connections to global public health – both philanthropic and the sovereign investors. Norway and Germany play outside roles in supporting global public health, and Japan has major commitments in this area, having long made investments in epidemic preparedness. Norwegian scientists and public health officials were instrumental in the only clinical trial for a vaccine during the Ebola crisis that generated definitive data on efficacy – that was the trial that took place in Guinea.

There was a global consensus that things did not go well with Ebola and that we didn’t want to be in a position again where we had vaccines that were almost ready but not quite. There was a real commitment to ensuring that we could buy the world a better insurance policy.

We’ve been actively engaged in further resource mobilisation efforts, and have had three further countries sign up to the coalition: Australia, Belgium and Canada. The collective commitment of these countries is smaller than the original investors and is, initially, limited to one year of investment but we are in active discussions to further this agreement with them. We are pursuing agreements with a number of sovereign partners and hopefully will be able to make announcements in the not too distant future about additional funding.

At present, we have secured $620 million towards our initial funding goal of $1 billion dollars. With the exception of the three smaller investments mentioned, all of our investors have committed to a five year agreement. To be clear, the $620 million will be used over a five-year time horizon.

What is the driving force behind CEPI?

I think Ebola is a really good illustration of the risk epidemic diseases represent and the unpredictability of that risk. Ebola is a disease that we’ve been familiar with for forty years, with around 30 outbreaks over this period. Some of these outbreaks had been fairly large, with the most significant causing around 400 deaths. However, all of those outbreaks had been contained within several months and it’s possible that the world had become a little bit complacent over Ebola. We hadn’t realised the importance of the social milieu and context to whether the outbreak would propagate. What happened in West Africa was there was a disease, which we thought we understood and thought we could control, which got into an environment where public health systems were poor but the road networks were good and the populations were concentrated. Suddenly, a disease that we thought we understood completely exploded.

There are other diseases, like Mers, Lassa and Nipah, that have been manageable to date but have characteristics that make them scary. We’ve seen this in quite public ways, for example in the epidemic in South Korea, where an individual instance gets into the hospital environment and becomes a super-spreader – suddenly, one case becomes a hundred cases. We went through a very careful selection process looking at the diseases on the WHO R&D blueprint list, thinking about their potential for outbreaks and the impact that they might have, as well as the likelihood that vaccines could be successfully developed. We went through a comprehensive screen of all the 11 diseases on the WHO list and mapping against those two dimensions, we prioritised the three diseases we are now focused on.

Is there now a growing concern over the threat infectious diseases pose?

There is a strong sense among public health officials, and there is data to back this up, that the tempo of these disrupting epidemics is increasing and it relates to many factors: growing population, intrusion into previously remote areas, better transportation networks, and greater concentrations of populations. We’ve seen the potential for, not just potential loss of life, but also significant disruption of national economies by epidemic diseases. All of these factors converge to increase the risk to a level greater than it has been previously. There’s always the risk that there will be a diseases that hasn’t had much focus, such as Zika or a new disease, to emerge and spread rapidly.

How is CEPI helping the world to prepare for such an eventuality?

We talk about our investments in terms of two categories: ‘just-in-case’ and ‘just-in-time’. Investments against Mers, Lassa and Nipeh, are ‘just-in-case’ investments, where we want to advance these vaccines to bring them much closer to being ready to deploy, either into clinical trials or emergency use authorisation.

Our investment in rapid-response platforms are part of the ‘just-in-time’ approach. The only vaccine platform that has been accepted by regulators is the influenza platform because they have to manufacture a new influenza vaccine every year. The regulators have become very comfortable if you swap in a new flu virus antigen, then they’ll accept the vaccine with a defined, but limited, amount of testing.

In 2009 in the US, it took about 26 weeks from the identification of H1N to the first doses of vaccine becoming available to the general public. At this time, there weren’t enough vaccines for the public before the late autumn wave of incidents had already come and gone. This means that even in influenza 26 weeks is not a long enough period of time to develop a vaccine and that’s on a platform that we are already familiar with.

Ebola began in late 2013 and really imprinted itself in the world’s consciousness in April/May time and then accelerated through the summer. The first large-scale clinical trials for an Ebola vaccine began in West Africa in early 2015, by that time the epidemic had basically been brought under control. The Ebola vaccines that entered clinical trials had been under development for the better part of a decade and had been developed not for epidemics but to combat the potential of bioterrorism. By the time things began to speed, there was over a decade’s worth of investment before they could be brought into clinical trials, and that was clearly too long.

That is the state of play today. CEPI wants to have these high-priority vaccines ready and sitting in stockpiles so that if there’s ever an epidemic then we can roll them right into clinical trials within weeks, not months or years.

Do we have a tendency to focus on the high-profile epidemics in high-intensity until they fade as a threat rather than being pre-prepared for emerging threats?

I think there has been a drum beat over the last 10 or 15 years, like SARS, Avian Influenza, Ebola, Mers, and Zika – you can’t predict the disease but there is a periodicity to threats emerging to global stability. There is a general awareness among global leaders across the political spectrum that infectious diseases pose global public health threats and security threats. Due to the latter risk, there is the possibility to secure sustained funding even when administrations change or political winds shift.

The concern with the general public is that infectious disease threats have a very limited hold on the public attention. When a public health threat is present or imminent they really want a vaccine but when the threat goes away, people tend to blot it out. Infectious diseases don’t knock buildings down, they just fill up graveyards. The memory of epidemics is very effervescent and that’s a problem when it comes to sustaining political will when it comes to preparedness.

SOURCE: www.pharmafile.com/news/515368

Global campaign to reduce cholera deaths by 90%

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A new campaign, launched by the WHO, has begun today to reduce deaths from cholera by 90% through to 2030.

The action will be instigated by the Global Task Force on Cholera Control (GTFCC), which is a network of 50 UN and international agencies, academic institutions, and NGOs that work to help countries struggling the most with the disease.

The push comes at a time when war-torn Yemen is facing the worst recorded outbreak of cholera that the world has ever seen – with 771,945 reported cases and 2,132 deaths. Globally, there are 2.9 million cases and approximately 95,000 deaths every year from the infection.

Cholera predominantly affects areas that have poor access to clean water supplies and poor sanitation facilities, it is most common in the poorest areas of the globe (see map above). The infection is relatively simple to treat, with rehydration salts offering a quick solution, and there has also been vaccine developed that offers protection from the bacteria for three years at a time.

The oral vaccine itself is cost effective, working out at only $6 per person – a development that the WHO referred to the availability of two vaccines as a “game-changer in the battle to control cholera, bridging the gap between emergency response and longer-term control”.

Cholera itself is an acute diarrhoeal infection, caused by the bacterium Vibrio cholera. It spreads through the contamination of water or food with the bacteria, in areas with poor sanitation, it can spread rapidly.

As can be seen in the map above, the infection is isolated to a select group of countries, with 47 countries affected by cholera and in 20 of these the disease is endemic; the Roadmap put forward by the WHO aims to rid up to 20 of the infection.

“WHO is proud to be part of this new joint initiative to stop deaths from cholera. The disease takes its greatest toll on the poor and the vulnerable – this is quite unacceptable. This roadmap is the best way we have to bring this to an end,” said Dr Tedros Adhanom Ghebreyesus, Director-General of WHO.

It is noted that Northern Europe and the US have managed to eliminate cholera 150 years ago. It is estimated that to provide all individuals with clean water, sanitation and hygiene the cost would amount to $40 per person.

SOURCE: www.pharmafile.com/news/515278

US steps up Ebola response

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The US government has bolstered its response to a potential Ebola outbreak by announcing plans to buy up more than a million doses of various treatments against the fatal virus.

The Biomedical Advanced Research and Development Authority (BARDA), which is part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the US Department of Health and Human Services, is to add four products to its stockpile.

These are a single-dose vaccine from Merck Sharp & Dohme, a two-dose one from Janssen Vaccines and therapeutic drugs from Mapp Biopharmaceutical (ZMapp) and Regeneron Pharmaceuticals (REGN3470-3471-3479).

The companies will be provided with so-called Project BioShield funding by BARDA to help with late-stage development and submission for regulatory approval with the US Food and Drug Administration.

Merck will receive $39.2 million, Janssen $44.7 million, Mapp $45.9 million and Regeneron $40.4 million. Part of the money will also be used to purchase the products themselves: BARDA can buy up to 1.13 million regimens of the drugs for a potential public health emergency.

Project BioShield is designed to protect Americans from bioterrorism, as well as naturally-occurring outbreaks, and this is the first time that Ebola – which US authorities believe could be a threat on both counts – has been included in funding.

“This marks a pivotal moment in US and global preparedness for future public health emergencies from viral haemorrhagic fevers like Ebola,” said BARDA Director Rick Bright. “We reached this point at unprecedented speed, and that’s a direct result of innovative approaches to product development and to partnering across the US government, other nations and private industry.”

Ebola outbreaks usually occur in African countries: in the most recent, from 2014-16, more than 28,600 cases of Ebola virus infection were either suspected, probable or confirmed and more than 11,000 people died, according to the World Health Organisation.

SOURCE: www.pharmatimes.com/news

‘Super malaria’ sweeps South East Asia

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There has long been concern over cases of drug-resistant malaria emerging in Asia and now it has been revealed that a particular strain of ‘super malaria’ has spread from Cambodia to Vietnam. 

The strain of malaria has developed to be resistant to both artemisinin and its partner treatment, piperaquine.

The incidence within Cambodia of the malaria is particularly high, with treatment alleged to be failing as often as 60% of the time. The spread to the south of Vietnam has caused concern that the multidrug resistant malaria may well spread further within Asia and potentially crossover to higher risk areas, such as India and, of more concern, Africa.

A recent letter to The Lancet, contained the following warning from researchers: “Artemisinin resistance is associated with mutations in the PfKelchgene. Initially multiple independent Kelch mutations were observed, but in a recent sinister development, a single dominant artemisinin-resistant P falciparum C580Y mutant lineage has arisen in western Cambodia, outcompeted the other resistant malaria parasites, and subsequently acquired resistance to piperaquine.”

The letter later goes onto state that the rise in cases are of “international concern”.

There are an estimated 214 million cases of malaria worldwide, which result in approximately 438,000 deaths. It is judged that 90% of these deaths occur in Africa and has experts worried that should this type of malaria manage to spread to the continent, it could have a devastating impact.

Already there is a 30% failure rate of the combination treatment in Vietnam, and the malaria has also spread into neighbouring Laos.

Co-author Professor Sir Nicholas White, of Mahidol and Oxford universities, said: “We are losing a dangerous race. The spread of this malaria ‘superbug’ has caused an alarming rise in treatment failures, forcing changes in drug policy and leaving few options for the future.”

The development of this treatment-resistant malaria is just part of a wider global trend towards ‘superbugs’ that are no longer manageable with current therapies. Around 700,000 people die per year as a result of drug-resistant infections.

SOURCE: http://www.pharmafile.com/news/515209

Pulses of light may offer ward against mosquitos

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Research emerging from scientists at the University of Notre Dame has found that exposing mosquitos to light during the night may dramatically change feeding habits of mosquitos.

It was found that just 10 minutes of exposure to light resulted in a greatly reduced habit to feed by the mosquitos.

The mosquitos used in the trial were Anopheles gambiae, which are the major contributors to the spread of malaria in sub-Saharan Africa – where 90% of deaths from malaria take place. It is hoped that by targeting this type of mosquito, the researchers can bring about actionable preventative measures that can be used in areas of high malaria occurrence.

The results are of some significance, as the researchers highlighted that traditional methods of keeping mosquitos at bay in the evening are becoming less effective as mosquitos adapt.

“Anopheline mosquitoes are adapting to these current methods by developing resistance to insecticides and by shifting feeding to earlier in the evening or later into the early morning, times of the day when people are not in bed and therefore not protected by a net. So what used to be an efficient method is becoming less effective,” said Giles Duffield, Associate Professor of Biology in the Department of Biological Sciences at the University of Notre Dame. “We need to discover new methods to address mosquito control and prevention. The systems and tools we currently have including global distribution and usage of insecticide-treated bed nets and spraying are not enough.”

The team tested two groups of mosquitos, those that were kept entirely in the dark and those that were exposed to pulses of white light for 10 minutes. The researchers then exposed their arms to the mesh lining that allowed mosquitos to feed while remaining contained, finding that the mosquitos exposed to light had a reduced inclination to feed.

In a further experiment, the mosquitos were exposed to light every two hours for a 12-hour period and found that they were also less likely to feed for this extended period.

The research opens the possibility of trialling different wavelengths of light, such as red light, that would disturb the sleep of those in the same room less. Beyond this, there is also scope to research whether different hertz of light may also have a greater effect.

SOURCE: www.pharmafile.com/news/514400