Category Archives: Gastroenterology

Gilead, Galapagos JAK inhibitor clears phase II test

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A mid-stage trial of Gilead and Galapagos’ JAK1 inhibitor filgotinib has set up a phase III programme for the drug in ankylosing spondylitis as it chases down two already-marketed dugs from Pfizer and Eli Lilly – and a late-stage rival from AbbVie.

In the TORTUGA trial, filgotinib met its clinical objective of reducing disease activity scores compared to placebo in patients with AS, a severe form of arthritis affecting the spine, with more patients achieving the target 20% improvement with the drug (76%) than in the control group (40%).

The drug is also in development for rheumatoid arthritis (RA), ulcerative colitis and Crohn’s disease with phase III trials already underway in those indications and results due in the coming weeks.

The drug was generally well-tolerated in TORTUGA but one case of deep vein thrombosis gave investors some cause for concern, putting some pressure on Gilead and Galapagos’ share price yesterday before share staged a partial recovery.

DVT is a recognised side effect with Eli Lilly’s JAK1 inhibitor Olumiant(baricitinib), which finally made it to market for rheumatoid arthritis in Europe last year but was rejected in the US at its first filing attempt over the safety issue. Gilead said that in the phase II AS trial the patient had an inherited condition that raised the risk of blood clots and the DVT was not thought to be drug-related.

First-to-market JAK inhibitor Xeljanz (tofacitinib) from Pfizer has already achieved $1bn-plus sales in RA, and with Olumiant somewhat hamstring by the safety issue on its label analysts are viewing the tussle between filgotinib and AbbVie’s upadacitinib as the next big battleground in the JAK inhibitor market.

AbbVie is a little ahead in the race to market, with phase III data in hand showing that upadacitinib is more effective than AbbVie’s $18bn-a-year injectable TNF blocker Humira (adalimumab) in RA when it comes to clinical responses gauged by doctors and patients. Like filgotinib, upadacitinib is also being tested in a string of other indications, including psoriatic arthritis, Crohn’s disease, ulcerative colitis and atopic dermatitis.

The rivalry is particularly strong as AbbVie was formerly Gilead’s partner for filgotinib, before ducking out of the collaboration and throwing its weight behind its in-house candidate.


Europe’s first allogeneic stem cell therapy rejected by NICE

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Cost regulators for the NHS in England and Wales have not approved funding for TiGenix and Takeda’s Alofisel – the first allogeneic stem cell therapy to be approved for use across the European Union – for use in Crohn’s patients.

The therapy (previously referred to as Cx601) was approved in March to treat complex perianal fistulas in adult patients with nonactive/mildly active luminal Crohn’s disease, when fistulas have shown an inadequate response to at least one conventional or biologic therapy.

Perianal fistulas, a common complication of Crohn’s disease, occur when an abnormal passageway develops between the rectum and the outside of the body, potentially leading to incontinence and sepsis. Complex fistulas, which are rare, are more treatment resistant than simple fistulas.

Alofisel (darvadstrocel) is a local administration of allogeneic (donor derived) expanded adipose-derived stem cells (eASCs).

In clinical trials underpinning the drug’s approval, patients receiving the treatment showing a 44 percent greater probability of achieving combined remission compared to placebo, while a follow-up analysis (at 52 weeks and 104 weeks post-treatment) confirmed sustained efficacy and safety, according to the firms.

However, in draft guidelines, the National Institute for Health and Care Excellence said Alofisel showed only a modest improvement in the proportion of people with complex perianal fistulas achieving complete remission compared with placebo in one clinical trial.

“Reliable follow-up results are only available for up to one year, so it is unclear how long the treatment benefit will last,” according to the guidelines.

Because of this, cost-effectiveness estimates are “highly uncertain” and the committee was unable to conclude on the most plausible cost-effectiveness estimate, NICE said.


Vertex says ‘some way’ to CF drug price deal after NHS meeting

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Representatives of Vertex Pharmaceuticals and NHS England met last week in an attempt to end a two-year long stand-off over the price of cystic fibrosis drugs – but there is still a long way to go before the matter is resolved.

Pressure from patient groups forced a parliamentary debate on access to Vertex’s CF drugs, after NICE rejected the company’s Orkambi combination therapy in 2016.

An online petition attracted more than 100,000 signatures, the threshold for a discussion in Parliament, and ministers have written to Vertex asking for the matter to be resolved.

Vertex is asking the NHS for a deal covering the price of its portfolio of CF drugs, including those that are yet to be approved, and will expand the proportion of the disease population who will be eligible for treatment.

The company confirmed in a statement that Vertex met with representatives of NHS England last Wednesday.

But a spokesperson added: “Both parties recognise there is still some way to go to reach an agreement and Vertex is committed to working together to achieve this. We share the cystic fibrosis community’s sense of urgency and have agreed to meet again in the coming weeks. There’s lots of work to do on both sides ahead of this to progress discussions as quickly as possible.”

However there is hope that there will be further progress in meetings over the coming weeks.

pharmaphorum understands that the biggest stumbling block is that NHS England wants to pay the same price as Vertex’s already-approved and NICE-backed Kalydeco (ivacaftor) for the company’s drugs.

Kalydeco’s list price is around £182,600 per year, although the company has agreed a confidential discount.

Cystic Fibrosis Trust public affairs manager Lynsey Beswick said: “We welcome the news that Vertex and NHS England have had further talks on the company’s medicines. This appears to be positive progress in our goal to gain access to the most advanced new medicines for people with cystic fibrosis at the earliest possible opportunity.”


Medicinal cannabis is safe and effective — it’s time to reboot research

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Researchers are calling for medicinal cannabis to be properly established in our modern medical arsenal.

Researchers claim that medicinal cannabis is safe and effective in pain relief, and are calling for the treatment to be properly established in our modern medical arsenal.

Cannabis has been used for centuries in pain relief, as a sleep aid and for many other purposes, yet there is little evidence on its safety and effectiveness. This is in part due to relatively recent legal restrictions on its use, which have hampered research efforts and resulted in doctors having little to no understanding of its use.

However, there has been an explosion in the number of studies published since 2012. The review provides two major studies on the use of cannabis in cancer patients and the elderly, as well as a comprehensive overview of the evidence, regulations, ethics and practical use. The authors and editors call for more research to improve the evidence base.

In a study led by Professor Victor Novack, A Professor at Ben-Gurion University of the Negev in Israel a team of researchers analysed data collected during the medicinal cannabis treatment of 2,970 cancer patients between 2015 and 2017. The two main problems patients were hoping to overcome were sleep problems and pain, and cannabis has been shown to be effective in alleviating both 95.9 percent of the patients reported an improvement in their condition.

The same team also analysed the effectiveness of medical cannabis in elderly patients who were being treated in 2015-2017 for a variety of issues, including pain and cancer. The researchers conclude in their paper: “Our study finds that the therapeutic use of cannabis is safe and efficacious in the elderly population. Cannabis use may decrease the use of other prescription medicines, including opioids. Gathering more evidence-based data, including data from double-blind randomised controlled trials, in this special population is imperative.”

In a review Professor Donald Abrams at University of California San Francisco Ward covers 10,000 scientific abstracts, “concluded that there was conclusive or substantial evidence that cannabis or cannabinoids are effective for the treatment of pain in adults; chemotherapy-induced nausea and vomiting and spasticity associated with multiple sclerosis.”

Yet the report also highlighted the barriers to research in the US, which may explain the lack of strong evidence for the therapeutic use of cannabis. This dearth of research has also led to numerous ethical issues in prescribing cannabis, not least because many doctors do not understand the treatment enough to advise dosage and use. An article by researchers at the University of British Columbia, Canada and International Cannabis and Cannabinoids Institute, Prague, Czech Republic provides practical guidance for doctors, with data on cannabis pharmacology.

“We feel it is absolutely imperative to not only present the current state of affairs but also propose the development of the scientific research program within the paradigm of evidence-based medicine,” said Prof Novack,  “Our ultimate aim should be to scientifically establish the actual place of medical cannabis-derived products in the modern medical arsenal.”


Queen’s University study could improve quality of life for bowel cancer patients

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The research study has been published in the prestigious Journal of Pathology, the world’s highest ranking journal in the field of molecular pathology.

A Queen’s University study could improve quality of life for bowel cancer patients.

Researchers are leading a ‘personalised medicine’ approach when it comes to treatment which could ultimately improve the prognosis and quality of life for bowel cancer patients.

They have demonstrated for the first time how molecular analysis of clinical trial biopsy samples can be used to help clinicians identify the key changes that occur in an individual patient’s bowel (colorectal) tumour prior to surgery, so clinicians can better understand and treat the disease.

The Queen’s led study, in collaboration with the University of Turin, University of Oxford, the University of Leeds and a number of clinical trial centres across the UK, demonstrates how personalised medicine can be successfully used to help improve outcomes in ongoing clinical trials.

Dr Philip Dunne, Senior Research Fellow from the Centre for Cancer Research and Cell Biology at Queen’s and joint senior author on the study, said: “There are approximately 1.4 million cases of bowel cancer diagnosed annually worldwide, with 41,000 cases in the UK each year. A number of treatment options are available but mortality rates remain high, with bowel cancer the second most common cause of cancer death in the UK.

“In order to develop better treatments for individual patients, we must first understand the biology of that person’s tumour; this is the basis of personalised medicine in cancer. Advances in molecular and genetic analysis in the past 10 years have markedly improved our biological understanding of colorectal cancer, although this increased knowledge it is yet to significantly change standard patient care. This study highlights how we can begin to use this new understanding developed in research laboratories, to identify the biology underlying an individual patient’s tumour in the clinic; the ‘bench-to-bedside’ approach.”

The research study has today been published in the prestigious Journal of Pathology, the world’s highest ranking journal in the field of molecular pathology.

Matthew Alderdice, a postdoctoral fellow on the project and first author on the study added: “Although molecular analysis is routinely carried out in research laboratories from large surgically removed tumours, in current clinical practice the tissue available for clinical decision-making may be only be the initial small tumour biopsy tissue. This study highlights how a precise understanding of the genetic changes that occur within this biopsy material is crucial to both understanding and treating the disease.”

Professor Mark Lawler, Chair in Translational Cancer Genomics at Queen’s said: “Molecular studies have indicated that a ‘one size fits all’ treatment approach for bowel cancer isn’t a viable option if we are to effectively tackle this disease. We have demonstrated the ability of molecular classification systems to stratify patients based on their molecular make-up in a series of colorectal biopsy samples obtained during a phase II clinical trial. The ultimate aim of this work is to allow patients to receive a more tailored disease management plan based on the specific biology of their tumour. Thus, we can tailor treatment to the individual patient, maximising its effectiveness while minimising potential side effects.”

This research study is part of the Stratification in Colorectal Cancer (S:CORT) consortium led by Professor Tim Maughan, from the University of Oxford and funded by a grant from the Medical Research Council (MRC) and Cancer Research UK (CRUK) as part of the MRC’s stratified medicine initiative.

Professor Tim Maughan, Professor of Clinical Oncology at the University of Oxford and Principal Lead of the S:CORT Consortium said: “This work highlights the benefit of a UK wide approach, bringing together the collective expertise within our consortium to drive new approaches to improve bowel cancer outcomes. Our S:CORT Consortium is gaining new insights into the key factors that influence bowel cancer development and its treatment and using this knowledge to maximise best treatment and quality of life for bowel cancer patients.”

S:CORT involves key partnerships with patients and patient advocacy groups. Ed Goodall, a survivor of bowel cancer and a member of S:CORT explains: “As patients, we are delighted to be involved in this work at a meaningful level, giving our opinions in relation to the scientific approaches that are undertaken within the consortium. As a citizen of Northern Ireland it is also extremely exciting to see the excellent work that is being done by researchers at Queen’s University.”

Deborah Alsina MBE, Chief Executive of Bowel Cancer UK and Beating Bowel Cancer, the UK’s leading bowel cancer charity and a partner in S:CORT, said: “We are delighted to be associated with this research. Our recent Critical Research Gaps in Colorectal Cancer Initiative highlighted the need for better research collaboration. This is an excellent example of the best UK science and clinical care in bowel cancer working together to develop innovative approaches to save more lives.”


Citing risk of ‘serious consequences,’ Bayer pulls Alka-Seltzer boxes listing incorrect ingredients

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Bayer is struggling with more than just sales at its important consumer health business.

This week, the company kicked off another Alka-Seltzer recall due to packaging issues.

In its second recall for the franchise in less than a year, the German drugmaker is pulling certain Alka-Seltzer Plus packages that were sold in Walmart, CVS, Walgreens and Kroger stores after Feb. 9. The packages might contain the wrong ingredients and could cause “serious health consequences,” the company said, but emphasized that none have been reported.


A Bayer spokesperson declined to say how many packages are affected.

The recall comes shortly after Bayer reported consumer health sales of €5.86 billion in 2017, a 1.7% decline from the prior year. The slip stemmed in part from “persistently weak business development in the United States,” CEO Werner Baumann said in a statement. Apart from problems in the U.S., Chinese officials switched two Bayer OTC skincare brands to prescription-only, denting sales there by €70 million, according to Bernstein analyst Jeremy Redenius.

Looking ahead, the drugmaker is expecting €5.5 billion in consumer health sales this year, which would mark another decline for the business. The guidance came up short of Wall Street’s €6 billion estimate.

Aiming for the top of the OTC food chain under former CEO Marijn Dekkers, Bayer picked up Merck’s consumer health assets for $14.2 billion back in 2014. But more recently, lower-margin businesses such as consumer healthcare and generics have come under increased pricing pressure in the U.S. To help get back on course, Bayer brought in former Nestlé exec Heiko Schipper in November to lead the consumer outfit.

GlaxoSmithKline, another top OTC drugmaker, grew 2017 consumer sales 2% at constant exchange rates to £7.8 billion.


Lab-grown tumours able to predict drug efficacy

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One of the key challenges facing the treatment of cancer is knowing whether a particular drug will work with an individual patient.

Of itself, this has led to some breakthroughs in the treatment of cancer, as treatments that specifically target gene markers have achieved success.

Researchers have now developed a method of testing drugs that could see doctors know which treatments will be successful before even beginning treatment. A collaboration between The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust has seen scientists grow “mini tumours” from biopsy samples, before testing various drugs on the cells.

The scientists were able to grow cells with a 96% similarity, and were able to predict, with 100% accuracy, which patients would not respond to certain drugs. In an added benefit, this method of testing was able to predict with 88% accuracy which drugs would be effective in producing a response in patients.

The hope is that this could later be used to determine the likelihood that a particular treatment would or would not work, thereby saving the patients the side-effects of a treatment with no benefit, and time to find a more effective treatment.

It would also allow for a reduction in cost across the healthcare system, as treatments that were shown not to work in grown tumours would not be tried – with some cancer treatments being among the most expensive to purchase.

The trial was based on biopsies taken from 71 patients with bowel, stomach or bile duct cancer, which had spread to others parts of the body. In total, 55 cancer drugs were tested on the tumours that were grown, which then allowed researchers to test the lab grown tumours response with the patients’ actual response.

Study leader Dr Nicola Valeri, Team Leader in Gastrointestinal Cancer Biology and Genomics at the ICR, and a Consultant Medical Oncologist at The Royal Marsden, said:

“Once a cancer has spread round the body and stopped responding to standard treatments, we face a race against time to find patients a drug that might slow the cancer’s progression and extend their lives. We found that recreating patients’ tumours in the laboratory using this new technique gave us an extremely promising way to predict whether a drug would work for a patient.

“We were able to look in incredible detail at how tumours responded to drugs – including patterns of gene activity and mutation, and even how the cancer would evolve in response to treatment. We looked at tumours from patients with cancers of the digestive system, but the technique could be applied to a wide variety of cancer types.”

The next step is to take the method into larger clinical trials and then determine how growing the cells would match up with a treatment timeline.


TiGenix’s Crohn’s fistulas treatment wins orphan drug status

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Belgian biopharmaceutical group TiGenix is one step closer to getting its first-in-class Crohn’s fistulas disease treatment to the US market following an orphan drug designation from the Food and Drug Administration (FDA).

The drug – currently known as Cx601 – could potentially treat ‘complex’ perianal fistulas in patients with Crohn’s disease who have had an inadequate response to at least one conventional or biologic therapy.

Dr Maria Pascual, vice president regulatory affairs and corporate quality, TiGenix, said: “The granting of orphan drug status by the FDA is a significant step forward in the Cx601 development programme.”

The designation follows results of the phase III ADMIRE-CD II trial, a randomised, double-blind, placebo-controlled study designed to confirm the efficacy and safety of Cx601 – a suspension of allogeneic adipose-derived stem cells.

It was found that a single dose of Cx601 was significantly more likely to heal perianal fistulas in Crohn’s patients and stop them coming back for at least a year compared to placebo.

Pascual added: “The FDA’s recognition of Cx601 as an orphan drug brings a number of potential financial benefits and is aligned with our ongoing work seeking expedited pathways towards product approval in the US.”

The move follows the FDA’s plan to eradicate its orphan designation backlog within 90 days, which was announced by commissioner Scott Gottlieb back in July this year.

Meanwhile, TiGenix and partner Takeda has said it will explore expedited pathways to accelerate the submission and review process for US regulatory approval of Cx601.


Celgene pulls plug on Crohn’s disease trials

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Celgene is abandoning late-stage testing of its experimental drug mongersen for Crohn’s disease after a Data Monitoring Committee concluded that it would be futile to continue.

The drugmaker confirmed the untimely end of the Phase III REVOLVE trial and the extension trial SUSTAIN following an interim assessment of the drug’s overall benefit/risk profile.

The company did stress that there were “no meaningful safety imbalances identified in the analysis,” but the move will still come as a huge disappointment, particularly as it also said the planned Phase III DEFINE trial in Crohn’s disease would now not be initiated.

According to the press release, “Celgene is waiting to review the full dataset from the phase II trial with GED-0301 in ulcerative colitis (UC) to determine next steps.”

“While we are disappointed with the results of REVOLVE, we remain committed to advancing our portfolio of novel medicines for patients suffering from this disease and other inflammatory bowel disorders,” said president and chief operating officer Scott Smith.

Mongersen (GED-0301) is an investigational oral antisense therapy that decreases Smad7 protein. In patients with Crohn’s disease, abnormally high levels of Smad7 interfere with anti-inflammatory pathways in the gut, leading to increased inflammation.