Novartis snatches Amgen and BMS veteran for CMO and Drug Development Head

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Dr John Tsai has been welcomed to the fold as Novartis’ new Head of Global Development and Chief Medical Officer, stepping into the role vacated by Dr Vas Narasimhan, who has since taken up the mantle of CEO at the company.

Dr Tsai will report directly to Dr Narasimhan and will also take up a position on the firm’s Executive Committee. He will commence the role on 1 May.

In his previous position, Dr Tsai served as Chief Medical Officer and Senior Vice President of Global Medical at Amgen since May 2017, managing all clinical and medical functions across Novartis sites worldwide. In his new role, Dr Tsai’s primary remit will be the advancement of the company’s drug pipeline, while also lead ongoing transformation within its Global Drug Development organisation which is looking to better leverage advanced data sciences and digital technologies.

Before joining Amgen, Dr Tsai worked for rival pharma firm Bristol-Myers Squibb for 11 years in a range of senior roles. Most recently, he was Global Head of Clinical Development for marketed products and global clinical operations at the company, and before this he served as Chief Medical Officer, Europe, and Head of US Medical and Vice President of Cardiovascular Medical prior to that. Earlier in his career, before his stint with BMS, Dr Tsai worked at Pfizer as a cardiovascular group leader.

“I am delighted to welcome John to Novartis,” remarked Dr Narasimhan. “As we continue to reimagine drug development, his expertise across multiple therapeutic areas, including cardiovascular, oncology and neuroscience combined with his background in electrical engineering will be a source of great strength for Novartis. John has a great track record in nurturing talent across clinical development, medical affairs and development operations and shares our commitment to build an empowered and inspired organisation. I also want to express my sincere gratitude to Rob Kowalski for his excellent ad interim leadership of the GDD organisation.”

Discussing his appointment, Dr Tsai said: “I feel honoured to have the opportunity to lead the Novartis Global Drug Development organisation and do my part in bringing forward the company’s strong pipeline of medicines that address some of humanity’s biggest health challenges. I am also excited to work with my colleagues at Novartis to pioneer novel paradigms for drug development with data and digital technologies at the core.”

SOURCE: www.pharmafile.com/news/517108

FDA clears first therapy for inherited rickets

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US regulators have approved the first drug to treat adults and children with x-linked hypophosphatemia (XLH), a rare, inherited form of rickets.

XLH causes low levels of phosphorus in the blood, leading to impaired bone growth and development in children and adolescents and problems with bone mineralisation throughout a patient’s life.

Ultragenyx Pharmaceutical and Kyowa Hakko Kirin’s Crysvita (burosumab-twza) is an antibody that blocks fibroblast growth factor 23 (FGF23), a hormone that causes phosphate urinary excretion and suppresses active vitamin D production by the kidney.

“The approval of Crysvita is truly a watershed moment for patients with X-linked hypophosphatemia as it is the first therapy directed toward correction of renal phosphate wasting,” said Tom Carpenter, lead study investigator, director of the Yale Center for X-Linked Hypophosphatemia, and Professor of Pediatric Endocrinology at Yale University School of Medicine.

“By targeting this mechanism Crysvita leads to sustained improvements in phosphate metabolism with concurrent repair of the skeleton, even after prior treatment with conventional approaches.

“Most importantly, the dosing regimen for Crysvita is far less burdensome than for currently available therapies and should be readily acceptable by families. I expect it to revolutionise the care of patients with XLH.”

SOURCE: www.pharmatimes.com/news

BRITISH AI FIRM RAISES £80M, VALUING IT AT £1.4BN

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London-based BenevolentAI has closed an £80m funding round which included investment from the US as well as from existing backers.

British artificial intelligence firm BenevolentAI has raised £80.8m, valuing the group at £1.4 bn and marking one of the largest funding rounds in the AI pharmaceutical sector.

The firm secured the funding from investors largely based in the US, as well as from existing backers such as Woodford Investment Management.

BenevolentAI is applying artificial intelligence to develop new medicines for hard to treat diseases. To date, it has raised more than £141m in funding since its launch in 2013.

The company will use this latest cash injection to ramp up its drug development, broadening the disease areas on which it focuses and advance these programmes to the clinic.

The group – Europe’s largest private AI company – will also use the funds to further develop its self-learning system, while also helping the firm to expand outside the pharmaceutical sector to other science-based industries, such as energy storage and agriculture.

Ken Mulvany, founder and chairman of BenevolentAI, said: “We are very pleased with the response to the fundraising. It reflects the rapidly growing global interest in the AI pharmaceutical sector and the recognition of our place as the dominant player within it.

“We have come a very long way since we founded the business in 2013. The capabilities of our technology didn’t exist six years ago.

“We are pioneering this sector and have evolved into a fully integrated, AI enabled drug development company with the ability to deliver better medicines at previously unimaginable speeds – this ultimately means patients will receive the right medicines, at a lower cost, in less time.”

BenevolentAI currently employs 165 people who work in a unique, cross functional environment that incorporates leading edge data scientists, computer scientists, mathematicians and drug development R&D scientists working side by side.

The company is headquartered in London with further offices in New York and Belgium. It also has a research facility at Babraham Science Park in Cambridge.

SOURCE: www.bqlive.co.uk/london-the-south/2018/04/19

Acoustic Cluster Therapy drives drug therapies to cancer cells

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Researchers are testing the use of pulsed sound waves to direct and focus cancer drug therapies.

Using in laboratory tests, researchers will analyse the effectiveness of a technology called Acoustic Cluster Therapy (ACT), a unique approach to targeting cancer cells by concentrating the delivery of chemotherapies, making them more effective and potentially reducing their toxicity.

South Korean manufacturers are developing clinically applicable hardware optimised for ACT, which the researchers at Translational Genomics Research Institute (TGen) will validate.

The researchers are using funding from Innovation Norway to conduct this research in advance of pancreatic cancer clinical trials planned later this year.

“We are very pleased to receive this grant, which will enable us to develop and validate an optimal ultrasound platform for clinical use of ACT. In their respective fields, Humanscan and TGen both represent the cutting edge of science, and we are confident this will contribute to the clinical success of our program,” said Dr Per Sontum, CEO of Phoenix Solutions.

“We are pleased that this research program has become a reality, and look forward to working with ACT. The concept represents a novel approach to targeted drug delivery and looks very promising,” said Dr Haiyong Han, a Professor in TGen’s Molecular Medicine Division and head of the Basic Research Unit in TGen’s Pancreatic Cancer Program.

Among the advantages of ultrasound technology: it is generally painless; non-invasive; does not require needles, injections or incisions; and patients are not exposed to ionising radiation, making the procedure safer than diagnostic techniques such as X-rays and CT scans.

Humanscan CEO Sungmin Rhim said, “We are excited to enter into this collaboration with Phoenix (Solutions) and participate in the development of ACT. Ultrasound-mediated, targeted drug delivery is an emerging therapeutic approach with great potential and we are delighted to be in the forefront of this development.”

The researchers are also is considering this technology for use in addressing other types of cancer, including liver, prostate and triple-negative breast cancer; and other diseases, including those involving inflammation and the central nervous system.

SOURCE: www.europeanpharmaceuticalreview.com/news/73776

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

Skin conditions cost NHS £723m a year

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New research shows that more than three million primary care hours are spent on skin conditions, at a cost to the NHS of £723 million each year.

The research, carried out by the Association of the British Pharmaceutical Industry in collaboration with an independent Dermatology Expert Working Group (EWG), highlights the burden of skin conditions on both patients and the NHS.

According to the findings, around 13.2 million people in England visited their GP with a skin problem in 2016, of which 85 percent said the psychosocial aspects of their condition were a significant part of their illness.

The research also showed that almost 60 percent of patients with severe psoriasis could lose up to 26 days of work a year because of their skin condition.

“Today’s findings bring into sharp focus the staggering amount of time and money the NHS spends on the management of skin conditions in primary care and the significant impact skin conditions can have on people’s lives,” said EQG chair Rt Hon Professor Paul Burstow.

“Ignore dermatology and we miss a huge opportunity to make real and immediate gains for the NHS and for people’s quality of life.”

The group’s report, Making real our shared vision for the NHS: optimising the treatment and care of people with long-term skin conditions in England, makes a stream of recommendations designed to drive efficiencies and improve patient outcomes.

It calls on NHS England to promote and support successful self-management through patient education programmes for specific long-term skin conditions, led by suitably trained healthcare professionals (HCPs), as well as promote promote and incentivise the adoption of technology such as email guidance and smartphone apps.

NHS England should also put in place suitable incentives to encourage commissioners to implement teledermatology pathways to triage patients with skin lesions appropriately and free up face-to-face time for clinicians to see patients with inflammatory skin conditions, it said.

SOURCE: www.pharmatimes.com/news

Celgene bucks trend to strengthen neuroscience pipeline

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Celgene has gone against industry movement to back out of the neuroscience area by putting down a potential $2.2 billion to gain options on three drug candidates held by Prothena.

The deal sees Celgene pay $100 million up front, alongside buying $50 million in shares of Prothena, with milestone payments on the three drugs potentially racking up to a total payment of $2.2 billion.

Whether Prothena will see anything of this money depends on how well each clinical candidate performs in Phase 1 trials.

The neuroscience area has not been blessed with a huge amount of good news of late, with Pfizer pulling out of the space and a raft of Alzheimer’s drugs flopping. Celgene backing the area as a long-term investment is welcome news, particularly in regards to Alzheimer’s research, with fears it could begin to flag after so many failures.

One of the candidates is a protein that targets tau. The build-up of tau protein in the brain is one hypothesis about how best to treat the degeneration linked with Alzheimer’s disease.

Prothena commented in the press release that it has “identified antibodies targeting novel epitopes on the tau protein with the ability to block misfolded tau from binding to cells and to inhibit cell-to-cell transmission, preventing downstream functional toxic effects.”

This could be of huge interest, after a number of the other major alterantive hypothesis, amyloid-targeting Alzheimer’s treatments, failed to show efficacy in trials.

The other named target was the protein, TDP-43, which is associated with amytrophic lateral sclerosis and dementia. There is one other protein that Prothena has chosen not to name as being a target, though this is still within the neuroscience space.

“Prothena has a legacy of innovation in neuroscience and a team with a deep understanding of biological approaches that target protein misfolding disorders. Our collaboration leverages each company’s core expertise in protein homeostasis and protein clearance to target proteins that are the underlying cause of many neurodegenerative and orphan diseases. The programs we have chosen to collaborate on have the potential to provide foundational assets from which we can build new therapeutic approaches to these currently untreatable neurological disorders” said Richard Hargreaves, PhD, Corporate Vice President Neuroscience and Imaging for Celgene.

Should Celgene choose to take any of these candidates further than Phase 1, it will be responsible for all global clinical development and commercialisation. Prothena will, in return, receive $80 million per candidate picked up.

SOURCE: www.pharmafile.com/news/516844

When antibiotics turn toxic

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Commonly prescribed drugs called fluoroquinolones cause rare, disabling side effects. Researchers are struggling to work out why.

In 2014, Miriam van Staveren went on holiday to the Canary Islands and caught an infection. Her ear and sinuses throbbed, so she went to see the resort doctor, who prescribed a six-day course of the popular antibiotic levofloxacin. Three weeks later, after she had returned home to Amsterdam, her Achilles tendons started to hurt, then her knees and shoulders. She developed shooting pains in her legs and feet, as well as fatigue and depression. “I got sicker and sicker,” she says. “I was in pain all day.” Previously an active tennis player and hiker, the 61-year-old physician could barely walk, and had to climb the stairs on all fours.

Since then, she has seen a variety of medical specialists. Some dismissed her symptoms as psychosomatic. Others suggested diagnoses of fibromyalgia or chronic fatigue syndrome. Van Staveren is in no doubt, however. She’s convinced that the antibiotic poisoned her.

She’s not alone. Levofloxacin is one of a class of drugs called fluoroquinolones, some of the world’s most commonly prescribed antibiotics. In the United States in 2015, doctors doled out 32 million prescriptions for the drugs, making them the country’s fourth-most popular class of antibiotic. But for a small percentage of people, fluoroquinolones have developed a bad reputation. On websites and Facebook groups with names such as Floxie Hope and My Quin Story, thousands of people who have fallen ill after fluoroquinolone treatment gather to share experiences. Many of them describe a devastating and progressive condition, encompassing symptoms ranging from psychiatric and sensory disturbances to problems with muscles, tendons and nerves that continue after people have stopped taking the drugs. They call it being ‘floxed’.

For decades, regulatory agencies and the medical profession were sceptical that a brief course of antibiotics could have such a devastating, long-term impact. But after persistent campaigning by patient groups, attitudes began to change in 2008, when the US Food and Drug Administration (FDA) announced the first of what would be a series of strong alerts about the side effects of fluoroquinolone drugs, including tendon rupture and irreversible nerve damage. In 2016, the agency accepted the existence of a potentially permanent syndrome that it calls fluoroquinolone-associated disability (FQAD), and recommended that the drugs be reserved for serious infections. That move has triggered other regulatory agencies to reassess the antibiotics: Health Canada warned doctors of rare cases of persistent or disabling side effects in January 2017, and the European Medicines Agency (EMA) is expected to publish the results of a safety review this year, after a public hearing planned for June.

Fluoroquinolones are valuable antibiotics, and safe for most people. Yet they are so widely prescribed that their side effects might have harmed hundreds of thousands of people in the United States alone, say scientists who are working with patients to unpick FQAD’s causes. Fluoroquinolone toxicity, they say, provides a compelling example of an emerging understanding that antibiotics don’t just harm microbes — they can severely damage human cells, too. Until recently, investigations into the side effects of antibiotics have focused on how the drugs disrupt the human microbiome, says James Collins, a medical engineer at the Massachusetts Institute of Technology in Cambridge. “Antibiotics are also disrupting our cells, and in pretty hefty ways,” he says.

The dark side of fluoroquinolones

Quinolone antibiotics, first developed in the 1960s, kill bacteria by blocking enzymes called class II topoisomerases, which normally untangle DNA during cell replication. These enzymes usually cut DNA’s double helix, pass another part of the strand through the gap, and then mend the cut. But quinolones bind to the enzymes, preventing them from mending their cuts. In the 1980s, researchers added fluorine atoms to the quinolones’ structures. This allowed the antibiotics to penetrate tissues throughout the body, including the central nervous system, and boosted their effectiveness against a broad range of bacterial infections.

Some FDA-approved fluoroquinolones were swiftly withdrawn from the market after severe adverse reactions and several deaths — trovafloxacin, withdrawn in 1999, damaged livers, for instance. But others became the drug of choice both for serious infections and for routine complaints, despite rare side effects. “These are heavily used drugs because they are very effective,” says Joe Deweese, a biochemist who studies topoisomerases at Lipscomb University College of Pharmacy in Nashville, Tennessee. In the 1990s, ciprofloxacin (cipro) was given to US troops serving in the Persian Gulf as prophylaxis in case of exposure to anthrax spores. And in 2001, sales of cipro surged after a series of terrorist attacks involving anthrax; the US Centers for Disease Control and Prevention (CDC) recommended a 60-day course for anyone at risk of being exposed.

But by that point, some people had already flagged potential problems. In 1998, US journalist Stephen Fried (now at Columbia Journalism School in New York) published a book called Bitter Pills about his wife’s severe and long-lasting neurological reaction to ofloxacin. It helped to trigger a wave of reports on websites such as the Quinolone Antibiotics Adverse Reaction Forum, which by 2001 hosted more than 5,000 posts. The late Jay Cohen, then a psychiatrist and medical researcher at the University of California, San Diego, contacted patients through the sites and published 45 case studies. Cohen warned that after taking fluoroquinolones, some people had developed serious problems in multiple organs. These effects came on rapidly and lasted for months or years.

Cohen’s work was largely dismissed at the time because of his reliance on online forums. But complaints and patient petitions continued. From the 1980s to the end of 2015, the FDA received reports from more than 60,000 patients detailing hundreds of thousands of ‘serious adverse events’ associated with the 5 fluoroquinolones still on the market (most commonly tendon rupture, as well as neurological and psychiatric symptoms), including 6,575 reports of deaths. The FDA says that the reports of adverse events it receives — sent in by drug manufacturers, by doctors and directly by consumers — cannot be used to reach conclusions about the severity of problems associated with drugs. Still, the fluoroquinolones have attracted more complaints than other more widely used antibiotics. And only 1–10% of adverse events are estimated to be reported to the FDA, suggesting that fluoroquinolones might have harmed hundreds of thousands of people in the United States alone, says Charles Bennett, a haematologist at the University of South Carolina’s College of Pharmacy in Columbia. Bennett is also director of the Southern Network on Adverse Reactions, a state-funded pharmaceutical-safety watchdog, which has been working with people affected by fluoroquinolones since 2010.

In 2008, the FDA announced ‘black box’ warnings of tendon rupture among those given the antibiotics; in 2013, it added a risk of irreversible nerve damage. (Such warnings are placed inside a black box on drug labels, and call attention to serious or life-threatening risks.) As alerts mounted, patients launched lawsuits against manufacturers of the drugs, claiming they had not been adequately informed of risks. These cases have been variously won, lost or settled for undisclosed sums, and many are still in progress; manufacturers argue that they handled risks appropriately, and work with the FDA to update safety labels.

In November 2015, the FDA voted to recognize FQAD as a syndrome on the basis of 178 cases that the agency regarded as clear-cut: otherwise healthy people who took fluoroquinolones for minor ailments and then developed disabling and potentially irreversible conditions. The FDA also noted a disturbing pattern: fluoroquinolones had a much higher percentage of disabilities among their serious-adverse-event reports than did other antibiotics.

Mitochondrial damage

Beatrice Golomb at the University of California, San Diego, has been working for a decade with people affected by fluoroquinolones, beginning with David Melvin, a police officer and keen cyclist who had to use a wheelchair after he was given levofloxacin for suspected epididymitis in 2007. Accumulating evidence, Golomb says, suggests that fluoroquinolones are damaging mitochondria, the power packs inside human cells that evolved from symbiotic, bacteria-like cells billions of years ago. This kind of harm can affect every cell in the body, explaining why a wide range of symptoms can appear and get worse over time.

Mitochondrial toxicity is a problem with many classes of drug, says Mike Murphy, who studies the biology of mitochondria at the University of Cambridge, UK. But because mitochondria retain some similarities to their bacterial ancestors, antibiotics can pose a particular threat to them. Researchers have shown, for example, that aminoglycoside antibiotics can cause deafness by damaging mitochondria in the hair cells of the ear.

Isolated studies from the 1980s onwards have suggested that fluoroquinolones impair mitochondrial function, but a 2013 study by Collins and his colleagues is the most convincing, researchers say. They reported that antibiotics in several classes triggered oxidative stress — a build-up of reactive, oxygen-containing molecules — in mitochondria, inhibiting their function across a range of mammalian cells, as well as in mice. “We were surprised at how strong the effect was and how common the effect was across the different classes,” Collins says. But “the largest effects were seen in the quinolones”.

Pharmaceutical researchers had spotted the issue, too: in 2010, toxicologist Yvonne Will and her colleagues at Pfizer in Groton, Connecticut, reported an assay to detect mitochondrial damage early in drug development. They found that some antibiotics affected mitochondria and others didn’t. Every fluoroquinolone they tested damaged mitochondria in human liver cells — having what the researchers described as “a strong effect” at therapeutic concentrations, although Will cautions that it isn’t possible to extrapolate from that result to clinical outcomes.

But the potential for mitochondrial damage still isn’t widely appreciated among antibiotics researchers and the medical community, Collins says. “I think people generally assume that antibiotics do not impact mammalian cells,” he says. One problem is that there is still no reliable biomarker that researchers can use to test for mitochondrial damage in people, tying cell-line research to clinical experience. Nor is it known precisely how the fluoroquinolones are damaging human cells. A 2013 FDA review of the antibiotics’ safety, for example, cited a 1996 study reporting that cipro caused DNA breaks in mitochondria in a variety of mammalian cell lines. But Neil Osheroff, a biochemist at Vanderbilt University in Nashville, Tennessee, who studies fluoroquinolones, is doubtful about that result. He has done his own lab tests, and found that, at therapeutic concentrations, the fluoroquinolones prescribed by doctors have very little effect on human DNA. Meanwhile, mitochondrial damage isn’t the only theory in play: a 2015 study, done on human kidney cells, reported that fluoroquinolones can bind to iron atoms from the active sites of several enzymes that modify DNA, leading to epigenetic changes that might be related to some of the drugs’ side effects.

At a conference last September, Bennett reported preliminary data that might hint at why only some people develop serious side effects from fluoroquinolones. He took saliva samples from 24 people who reported neuropsychiatric side effects — such as memory loss, panic attacks and depression — and found that 13 of them (57%) shared a gene variant usually seen in only 9% of the population. Bennett is not revealing the gene’s identity because he has a patent application in process, but he says that it seems to be a site related to poor metabolism of the quinolones. Such a mutation might cause dangerously high levels of the drug to accumulate in cells, including in the brain. Bennett is now conducting a trial with 100 more participants to see if he can replicate the result. If so, that might lead to a genetic test to identify people who should not be given the drugs.

Lack of support

Most scientists asked by Nature about fluoroquinolones said that more research is needed to understand their side effects. Collins hopes to explore mitochondrial damage by antibiotics in other animal models. He and Murphy have also found, in lab studies, that giving antioxidants alongside fluoroquinolones seems to mitigate the effects on mitochondria. Murphy is interested in trials to avoid mitochondrial toxicity in drugs; he owns shares in a company that aims to set some up. But such trials are difficult and expensive, particularly for drugs that are given in sometimes life-threatening situations, he says. Golomb is currently conducting an unfunded online survey to gather information on the experiences of thousands of patients. She hopes that it will lead to hypotheses about what might mitigate harms that could then be tested in clinical trials. But little support is available. That’s typical for research on drug safety. Investigating medications that have been on the market for years isn’t a priority for research agencies such as the US National Institutes of Health, says Bennett. Manufacturers don’t have an incentive to fund post-market safety studies, particularly for off-patent drugs such as cipro and levofloxacin, where the vast majority of sales are from generics firms. “So there is really nobody to champion this work,” says Bennett.

Another factor is scientists’ reluctance to publish results that drug companies might find unfavourable. “There’s a long history of adverse action against people who expose drug and chemical harms,” says Golomb. She cites a list made by the pharmaceutical firm Merck of doctors who criticized the anti-inflammatory drug Vioxx (rofecoxib), which was withdrawn from the market over an increased risk of heart attack and stroke. According to internal e-mails read out in court in 2009 as part of a Vioxx class-action case in Australia, a list e-mailed among Merck employees contained doctors’ names with the labels “neutralize”, “neutralized” or “discredit” next to them. (Merck did not respond to Nature’s request for comment.) Aggressive tactics are “a very big problem”, says Bennett, who says he has been threatened by drug companies in the past.

For Osheroff, there are more-pressing concerns about fluoroquinolones, such as how to combat the emergence of antibiotic-resistant infections and develop new antibiotics. But he and other scientists agree that doctors should not prescribe fluoroquinolones for relatively minor infections when they could use other drugs. The FDA’s warnings on drug labels, however, have been slow to produce results. Prescriptions for the drugs did not fall between 2011 and 2015, according to the CDC (see ‘Overprescribed antibiotics’). This suggests, says Bennett, that official alerts haven’t been enough to get physicians to change their habits. The labels for fluoroquinolones alone have changed around 20 times in the past 4 or 5 years, he says. “It is almost impossible for doctors to keep up.” Still, US prescriptions of fluoroquinolone antibiotics did drop by around 10% in 2016, and totals for the first half of 2017 suggest that prescriptions fell again last year, according to unpublished figures given to Nature by IQVIA, a health-data firm in Durham, North Carolina.

Meanwhile, van Staveren, in Amsterdam, complains that despite her medical training, she still can’t find a doctor who believes her. She is waiting for the EMA to make its recommendations, and hopes that it will follow the FDA in acknowledging FQAD, and warning about it. (The EMA declined to comment while the review is ongoing.) “I want doctors to be informed about the risks, no matter how rare or not they are,” van Staveren says. “I want warnings all over and I want the warnings to be taken seriously.”

SOURCE: www.nature.com/articles

Five new medical schools to open under ‘biggest ever expansion’ of medical training

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Five new medical schools will launch across in England in September as part of the government’s ‘biggest ever expansion’ of the NHS medical workforce, the DHSC has announced.

The new medical schools will open in Sunderland, Lancashire, Canterbury, Lincoln and Chelmsford. They have been ‘chosen as part of a rigorous bidding process to help place more medical students in areas which traditionally struggle to attract doctors, particularly rural and coastal areas,’ the DHSC said.

As part of the plans to increase the medical workforce the government is also funding 100 additional places at Aston University’s medical school in Birmingham. Twenty further medical schools will also have additional student places funded.

The DHSC said that by 2020 there will be an extra 1,500 doctors in training. Some 630 of these places will be available from September, taking the total number of medical students for 2018/19 to 6,701, which the DHSC said was the highest on record.

The five new medical schools will be based at:

  • University of Sunderland
  • Edge Hill University in Lancashire
  • Anglia Ruskin University in Chelmsford
  • Lincoln – The University of Nottingham in partnership with the University of Lincoln
  • Canterbury – Joint medical school between Canterbury Christ Church University and the University of Kent

Health and social care secretary Jeremy Hunt said: ‘Setting up five new medical schools is part of the biggest ever expansion of our medical and nursing workforce; which will help us deal with the challenges of having around one million more over 75s in ten years’ time.

‘These schools are being set up in parts of the country where it is can be hard to recruit and attract new doctors – but will benefit doctors everywhere as we start to eliminate the rota gaps that add so much pressure to their work.’

SOURCE: www.gponline.com

Row over CF drug funding as NHS rejects Vertex offer

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A deal covering new cystic fibrosis drugs is unlikely to happen unless the manufacturer Vertex agrees to drop its prices, NHS England has indicated.

Vertex is seeking a deal to fund national access in England to its cystic fibrosis (CF) drug, Orkambi (lumacaftor+ivacaftor),  a combination which extends the number of CF whose underlying disease can be treated.

Over the last 12 months NHS England has taken a lead role in negotiating directly with pharma companies, and has created a dedicated Commercial Medicines Unit for the task.  Faced with static NHS budgets and growing budget pressure, it is taking a harder line on prices, but also says it is willing to negotiate deals based on outcomes.

However no such deal has been struck on this occasion. In fact CF campaigners have reacted angrily to this NHS England rejection, and Vertex is critical of how the budget holder has conducted the discussion, saying NHS England has only communicated via email.

MPs are set to debate availability of cystic fibrosis drugs in Parliament later today, after a petition calling for them to be funded by the NHS attracted more than the 100,00 signatures.

But for now NHS England has said it is not interested in a deal covering cystic fibrosis drugs, despite the growing pressure from campaigners.

Vertex is keen to get its CF drugs funded in England and the wider UK because of the high number of patients with the disease here.

With 10,000 patients affected, the UK has the second highest number of CF patients in the world and as such would be an important and valuable market for Vertex.

The manufacturer is seeking a deal that would cover Orkambi and any other future CF drugs that it develops as part of a “portfolio approach”.

This was sparked by NICE’s decision to reject Orkambi in 2016, which was too expensive for NICE despite discounts and greater flexibility in funding for rare disease drugs.

Although the negotiations over pricing are confidential, campaigners united under the hashtag #ukneedsorkambi are speculating that NHS England wants Vertex to expand the number of patients receiving treatment from 400, to almost 4,000 but without receiving any extra funding.

Pharmaphorum quizzed NHS England on the details of the negotiations, and a spokesperson responded with a short statement.

The spokesperson said: “The NHS can only offer treatments which are both effective for patients and offer good value for taxpayers, so it’s crucial that drugs companies work with the NHS to get a positive outcome.”

“Following advice from NICE, the NHS has asked this particular drug company to review its proposed pricing, and unless this happens further progress at this time is frankly unlikely.”

A Vertex spokesperson said the company is “astonished and dismayed” with NHS England’s response.

“It amounts to a refusal to make any additional funding available for Orkambi or future medicines,” a company spokesperson said.

“Cystic fibrosis (CF) is a devastating disease where half of people die by the time they are age 31. The situation with CF in the UK is unique and needs a unique solution – this is what our portfolio approach that we proposed in February offers.”

“Negotiations over email are rarely productive and CF patients do not have time to waste. We call on all parties to come to the table to engage in meaningful dialogue about a way forward – on behalf of CF patients.”

SOURCE: www.pharmaphorum.com/market-access-2