New guideline clarifies role of radiation therapy in pancreatic cancer treatment

First-of-its-kind clinical guideline from leading radiation oncology society discusses radiation dosing, conventional versus stereotactic radiation and mitigating side effects

A new clinical guideline from the American Society for Radiation Oncology (ASTRO) provides recommendations on the use of radiation therapy to treat patients diagnosed with pancreatic cancer, including when radiation treatments are appropriate, as well as the optimal dosing, timing and fractionation for these treatments. The guideline, which also outlines strategies to prevent and mitigate common side effects of pancreatic radiation therapy, is published online in Practical Radiation Oncology, the clinical practice journal of ASTRO.

Despite being the 11^th most common cancer diagnosed among U.S. adults, pancreatic cancer is the third leading cause of cancer death, with an estimated 45,570 deaths and 56,770 new diagnoses in 2019. The five-year relative survival rate for pancreatic cancer is 9%, which is among the lowest for any cancer type. Multiple factors underlie these high mortality rates: the disease is very aggressive compared to other cancers, symptoms can be vague, and screening is difficult. More than half of diagnoses occur after the cancer has metastasized, when the five-year relative survival rate drops to 2.9%.

The ASTRO guideline covers four main areas: (1) the use of radiation in pre-surgical, post-surgical, definitive and palliative treatment settings; (2) stereotactic versus conventional radiation therapy; (3) technical aspects of radiation therapy; and (4) mitigating common side effects. It emphasizes a patient-centered approach that integrates patients' values and preferences into treatment decisions and also stresses the importance of multidisciplinary consultations, planning and follow-up.

Standard treatment for localized pancreatic cancer, or disease that has not spread outside of the pancreas, involves surgery to remove the tumor, combined with radiation and/or chemotherapy prior to surgery and/or following surgery to target potential residual disease. More than 80% of patients are diagnosed with tumors that have spread beyond the pancreas and cannot be removed surgically, however, and even patients who undergo surgery face local and distant recurrence rates of 50-90%.

Recent breakthroughs including new systemic therapies and the emergence of stereotactic radiation have driven significant changes in pancreatic cancer treatment, which led ASTRO to develop its first guideline on this topic. "Historically, very high rates of distant metastatic disease with pancreas cancer have overshadowed its tendency to recur locally. In the past several years, newer systemic therapies are proving to be more effective at controlling this cancer when it spreads, and fewer people are dying from distant disease. This makes treatments like radiation to manage local disease more meaningful," explained Manisha Palta, MD, co-chair of the guideline task force and a radiation oncologist at Duke University.

Recommendations for Radiation Therapy for Pancreatic Cancer Patients

The guideline first presents indications for radiation therapy in the adjuvant, neoadjuvant and definitive settings. It delineates between conventionally fractionated and stereotactic radiation therapy, providing the first clinical guidance on the newer, shorter-course approach. "One thing this guideline offers that hasn't been available previously is context about the current status of ablative radiotherapy such as stereotactic body radiation therapy (SBRT) and where it might be useful for patients with pancreatic cancer," said Dr. Palta.

Recommendations on the indications of radiation therapy for pancreas cancer are as follows: 

• In the adjuvant/post-operative setting, conventionally fractionated radiation is recommended conditionally for patients with high-risk features such as positive lymph nodes and margins following surgical resection. SBRT is recommended only if the patient is enrolled in a clinical trial/data registry.
• In the neoadjuvant/pre-operative setting, conventionally fractionated radiation therapy or SBRT is recommended conditionally following chemotherapy for patients with resectable disease. Neoadjuvant chemotherapy plus radiation (either conventional or stereotactic) is conditionally recommended following systemic therapy for select patients with borderline resectable disease.
• For patients with locally advanced disease (who are not candidates for surgery), systemic chemotherapy followed by either chemoradiation or SBRT is recommended conditionally as an option for definitive treatment.

Recommendations also address: 

• optimal dosing and fractionation for different subgroups of patients;
• sequencing of radiation with systemic chemotherapies in adjuvant, neoadjuvant and definitive settings;
• simulation and setup strategies, such as image guidance and patient-specific motion management;
• techniques for treatment planning and delivery, including a strong recommendation for the use of modulated radiation therapy to deliver treatment; and
• treatment in the palliative setting, including a strong recommendation for palliative radiation therapy to either the primary tumor or select metastatic sites to help relieve the patient's pain and other symptoms.

Mitigating Side Effects 

The guideline also addresses ways to mitigate side effects related to pancreatic radiation, whether given alone or with chemotherapy. While the side effects from radiation therapy depend on how the radiation is administered, the most common toxicities include fatigue and digestive/gastrointestinal effects such as nausea, vomiting and diarrhea.

The guideline strongly recommends that patients who undergo radiation treatments for pancreatic cancer be given prophylactic anti-nausea medicines. It also conditionally recommends the use of antacid or acid-reducing medications.

Dr. Palta explained how these medications are used preventatively with radiation: "If we know that certain side effects tend to occur with a relatively modest or high frequency – such as nausea and stomach pain – there are medications we can give to patients prior to treatment to help mitigate those side effects."

Future Directions

The guideline comments on emerging and upcoming trial reports that will add to the evidence on stereotactic radiation and other aspects of pancreatic cancer treatment, and which subsequently will shape future clinical practice and guideline updates.

"Any patient who is diagnosed with pancreatic cancer deserves to have a multidisciplinary evaluation, where she or he can have nuanced conversations about the benefits and risks of different types of treatment based on the most current information available. It's also essential that any patient who might be an appropriate candidate for radiation have access to a radiation oncologist who can provide perspective on the pros and cons of treatment, so that the patient can make an informed decision," said Dr. Palta. “This is a rapidly evolving field and some potentially practice-changing studies that are not included in this guideline may become available in the relatively near-term future.”

About the Guideline

The guideline was based on a systematic literature review of 179 articles published from May 2007 through January 2017. The 14-member task force included a multidisciplinary team of radiation oncologists from a variety of practice settings, a medical physicist, a medical oncologist, a surgical oncologist, a radiation oncology resident and a patient representative. The guideline was developed in collaboration with the American Society of Clinical Oncology (ASCO) and the Society of Surgical Oncology (SSO), who provided representatives and peer reviewers.

ASTRO's clinical guidelines are intended as a tool to promote appropriately individualized, shared decision-making between physicians and patients. None should be construed as strict or superseding the appropriately informed and considered judgments of individual physicians and patients.                      

“Radiation Therapy for Pancreatic Cancer: An ASTRO Clinical Practice Guideline” is available as a free access article in Practical Radiation Oncology, ASTRO’s clinical practice journal. For a copy of the guideline or to interview the task force chairs or outside experts in pancreatic cancer, contact ASTRO’s media relations team at press@astro.org or 703-286-1600.

Additional Resources on Pancreatic Cancer and Radiation Therapy

• PDF: Questions for patients diagnosed with pancreatic cancer to ask when considering and receiving radiation therapy
• PDF: An overview of the pancreatic radiation treatment process
• Blog: New ASTRO guideline offers recommendations on RT indications and technique in pancreatic cancer

ABOUT ASTRO
The American Society for Radiation Oncology (ASTRO) is the world’s largest radiation oncology society , with more than 10,000 members who are physicians, nurses, biologists, physicists, radiation therapists, dosimetrists and other health care professionals who specialize in treating patients with radiation therapies. The Society is dedicated to improving patient care through professional education and training, support for clinical practice and health policy standards, advancement of science and research, and advocacy. ASTRO publishes three medical journals, International Journal of Radiation Oncology • Biology • Physics, Practical Radiation Oncology and Advances in Radiation Oncology; developed and maintains an extensive patient website, RT Answers; and created the nonprofit foundation Radiation Oncology Institute. To learn more about ASTRO, visit our website, sign up to receive our news and follow us on our blog, Facebook, Twitterand LinkedIn.

Find time for fitness this STRESS-tember

There’s a reason it’s known as STRESS-tember. You have too much to do at work, at home, and in your social life and healthy habits take a back seat because you’re just ‘too busy.’

The reality is Canadians are fitting more activities than ever into their days. In a national survey of working Canadians, one-third of respondents feel they have more work to do than time permits. That number rises to 40 per cent when family roles are taken into account. 
 

We’re so busy we tell ourselves we don’t have time for anything else…especially exercise. In another Canadian study, 44% of respondents said they had no time for regular physical activity and almost a third (31%) said they end up spending time commuting instead of being physically active.

According to Nsuani Baffoe, personal training manager for downtown Toronto with GoodLife Fitness, a lot of this chronic busy-ness is not always as bad as it seems, and it’s possible to find time for exercise. In fact, the busier and more stressed out you are, the more you can benefit from a workout. Exercise increases your overall sense of wellbeing and contributes to endorphin production, which makes you feel happier and more content. It also helps you sleep better and think more clearly, to better multi-task your way through it all. 

The key is to take a look at the time-sucking activities (hint: it’s staring at screens) and FIND the time to exercise and prepare healthy food options. To get the right amount of exercise all we need is 1.8% of our time - just one hour three times a week. 

Some ways to escape your stress and fit in a workout include:

Take stock of your time use. Track your activities for a few days. You may find you’re not quite as busy as you feel – maybe you spend 15 minutes every morning scrolling through social media, or you watch TV every night for two hours. Identify non-essential activities that are slowing you down and reassign that time to physical activity. 

Schedule your workout like an appointment (and stick with it). By putting exercise into your calendar, you’re making it a priority, equal to work, paying the bills, shopping for groceries. It’s also more difficult to cancel when it’s right there in your calendar. 

Tailor workouts to how you’re feeling. If you’re exhausted and stressed, you want a workout that will leave you feeling stronger and revitalized. Baffoe suggests yoga or Pilates routines for stress-release and posture improvement. Or try a simple bodyweight circuit with squats, lunges, push-ups, and crunches. Strength exercises can be done anywhere and are great for posture and toning. Bonus: both workouts help you sleep better. 

Be more efficient. Try HIIT or Tabata workouts if you’re short on time. This approach means you push yourself for a short time, followed by less rest, so your work is over sooner. Just 15 minutes of HIIT (combining cardio and strength moves) once a week can have the same benefits as about 300 minutes of cardio. 

Simplify your goals. If your goals are too ambitious, there’s a good chance you won’t achieve them. Try setting more bite-sized, easy goals you know you can achieve. Instead of ‘hit the gym for one hour every day’ try ‘do something active every day and hit the gym 3-4 times this week.’

Build exercise into your work and family time. At work: ditch the car and commute by bike, take regular breaks for stretching and exercise, and schedule walking meetings. Friends and family: Meet up for a group fitness class, take advantage of the fall months to jump on your bikes and tour the neighbourhood, or take the dog to the park to reconnect with your loved ones. 

Nsuani Baffoe and fitness experts in your area are available to talk more about the best approach to fit in more exercise into your busy routine in STRESS-tember and beyond. They can demonstrate time-saving workout ideas (HIIT and Tabata), as well as some great exercises to reduce stress and maximize the impact of every workout.

ETNA-AF Registry Data Provide Real-world Evidence of the Efficacy and Safety Profile of LIXIANA® (edoxaban) in Elderly Non-Valvular Atrial Fibrillation Patients

MONTREAL, Sept. 4, 2019 /CNW Telbec/ - Servier Canada announces one-year outcomes results from a study of 24,962 patients with non-valvular atrial fibrillation (NVAF) treated with LIXIANA^® (Edoxaban), including elderly NVAF patients and those with and without a history of intracranial haemorrhage (ICH). One-year follow up data from the ETNA-AF (Edoxaban Treatment in routiNe clinical prActice) study were presented at ESC Congress 2019 in Paris, France, reporting the effectiveness and safety of LIXIANA in patients with NVAF.

Global ETNA-AF analyses

A new analysis, which reported the outcomes of 24,962 edoxaban-treated patients with NVAF at one year follow up supports the treatment's safety and efficacy profile in elderly and very elderly AF patients. The majority of these patients were aged 65 years or over.^[1] Results showed that:^[1]

• Rates of major bleeding (MB), as defined by the International Society on Thrombosis and Haemostasis (ISTH), including ICH and ischaemic stroke were generally low amongst all patient groups. Per year, ISTH-defined MB occurred in 0.6% of patients aged <65, 0.9% patients aged ≥65-<75, 1.2% patients aged ≥75-< 85 and 1.8% patients aged ≥85. ICH occurred in 0.2% patients aged <65, 0.3% patients aged ≥65-<75, 0.3% patients aged ≥75-< 85 and 0.3% patients aged ≥85. Ishaemic stroke occurred in 0.6% of patients aged <65, 0.7% patients aged ≥65-<75, 0.9% patients aged ≥75-< 85 and 1.3% patients aged ≥85. 
• Whilst all-cause and CV mortality was shown to increase with age, as would be expected, CV mortality was a minor proportion of all-cause mortality in all age groups. There was also no increase in the rate of ICH with age. Per year, all-cause mortality/CV mortality occurred in 35 (1.1%)/18 (0.5%) of patients aged <65, 136 (1.8%)/62 (0.8%) of those aged ≥65-<75, 275 (3.3%)/116 (1.4%) of those aged ≥75-<85 and 196 (8.7%)/76 (3.4%) of those aged ≥85. 

"These findings are important because the prevalence of NVAF and stroke risk, and therefore the need for oral anticoagulation, all increase with age," said Professor Raffaele De Caterina, Professor of Cardiology, Institute of Cardiology at the University of Pisa, Italy. "Additionally, elderly patients are more likely to have other comorbidities and to be on various medications that may interfere with treatment. The data from this set of unselected patients support edoxaban's growing evidence of safety profile and its use as an effective treatment for elderly, and very elderly, AF patients in regular clinical care. Of particular interest is the set of data showing no apparent increase in the rate of intracranial haemorrhage in edoxaban-treated patients as a function of age, while a high rate of this occurrence and its increasing prevalence as a function of age was shown in warfarin-treated patients." 

Additionally, a further 1-year follow-up analysis of the difference in outcomes between edoxaban-treated AF patients with history of ICH (i.e. those at higher risk of stroke, death and recurrent haemorrhage) and those without a history of ICH, showed that:^[2]

• Incidences of ISTH-defined MB (including ICH) and clinically relevant non-major bleeding (CRNMB) were generally low in both groups. 
• ICH occurred in 3 (1.2%) patients with history of ICH and 56 (0.3%) patients without history of ICH, per year. The rate of ischaemic stroke was higher in patients with history of ICH (6 [2.4%]) than in those without (165 [0.8%]), per year.

These new data suggest that edoxaban is an effective treatment option for patients with or without prior ICH, whilst also demonstrating the need for effective stroke prevention in NVAF patients with a history of ICH.^[2]

"The global ETNA AF programme is the largest and most comprehensive repository of real-world data on the use of a DOAC, in this case Lixiana®. The sub-group analysis of the elderly/very elderly AF patients of this registry, which represents more than 21,000 patients, provides further evidences about the safety profile of Lixiana® in populations at high risk of bleeding. It also complements, the recently published ENTRUST-AF PCI results confirming the safety profile of Lixiana® in AF patients undergoing a successful PCI", mentioned Frederic Fasano, CEO of Servier Canada.

Further new European analyses at ESC 2019 

Echoing the Global registry outcomes data, additional one-year follow up analyses of 12,574 unselected elderly AF patients with comorbidities, from ten European countries, showed that the incidence of clinical events for both bleeding and stroke rates were low. Per year, MB occurred in 1.05% (n=125), ICH occurred in 0.23% (n=28) and any stroke or systemic embolic events occurred in 0.82% (n=98) of cases.^[2] All-cause mortality occurred in 3.55% of patients per year, which can be rated as low in a high-risk context.^[3]

This snapshot real-world analysis compared the baseline and first year outcomes data from 12,574 patients (mean age of 73.6 years) with the outcome data of the European cohort from the clinical Phase III ENGAGE AF-TIMI 48 study,^[3] which investigated the safety and efficacy of edoxaban compared to warfarin, for the prevention of stroke or stroke and systemic embolic events in patients with AF.^[4] In ETNA-AF, edoxaban was used in a broad range of elderly NVAF patients. Additionally, dose reduction at baseline between the ETNA-AF and ENGAGE AF-TIMI 48 was similar and overall there was a good adherence (84%) to the European label.^[5]

"It is interesting to note that the higher HAS-BLED score in ETNA-AF compared to ENGAGE AF-TIMI 48 suggests that in real-world clinical settings physicians are more comfortable using edoxaban in patients with higher bleeding risk," said Raffaele De Caterina, Professor of Cardiology, Institute of Cardiology at the University of Pisa, Italy. "This new analysis reinforces the safety profile and effectiveness of edoxaban in elderly NVAF patients at high CV risk, but also suggest that the ENGAGE AF-TIMI 48 study efficacy results are being largely confirmed in general practice." 

About ETNA-AF 

ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with nonvalvular Atrial Fibrillation) is a global programme that combines data from distinct non-interventional studies in Europe, East Asia, and Japan in a single database. A total of more than 28,000 patients will be included in the ETNA-AF registries and followed for two years (patients in Europe will be followed for four years). The primary objective of ETNA-AF is to collect information on the use of edoxaban in routine clinical practice, including the safety and efficacy profile in non-preselected patients with NVAF.^{[6],[7],[8],[9],[10]} 

About Atrial Fibrillation

AF is a condition where the heart beats irregularly and rapidly. When this happens, blood can pool and thicken in the chambers of the heart causing an increased risk of blood clots. These blood clots can break off and travel through the blood stream to the brain (or sometimes to another part of the body), where they have the potential to cause a stroke.^[11]

AF is the most common type of heart rhythm disorder affecting approximately 350,000 Canadians and is associated with substantial morbidity and mortality.^[12],[13] Compared to those without AF, people with the arrhythmia have a 3-5 times higher risk of stroke.^[14] One in five of all strokes are a result of AF.^[15]

About Edoxaban

Edoxaban is an oral, once-daily, direct factor Xa (pronounced "Ten A") inhibitor. Factor Xa is one of the key components responsible for blood clotting, so inhibiting this makes the blood thin and less prone to clotting. Edoxaban was discovered and developed by Daiichi Sankyo Co., Ltd. On June 27, 2016, Daiichi Sankyo and Servier Canada entered into an agreement whereby Servier Canada would market the oral, once-daily anticoagulant edoxaban in Canada, upon approval by the Canadian health authority. Edoxaban is currently marketed in more than 30 countries and regions around the world.

About Servier Canada 

Servier Canada is an affiliate of the independent French Servier Group governed by a Private Foundation. We, at Servier, are committed to therapeutic progress to serve patient needs. We work assiduously to provide the Canadian medical community and its patients with innovative therapeutic solutions. As such, Servier Canada is partnering with various players in the life science ecosystem including researchers, clinicians, entrepreneurs and innovators. In addition to these research partners, the International Center for Therapeutic Research (ICTR) located in Laval, is dedicated to preclinical and clinical development with more than 50 studies conducted throughout Canada over the last 10 years. More information is available at www.servier.ca

About the Edoxaban Clinical Research Programme

More than 10 studies, more than 100,000 patients worldwide

Daiichi Sankyo, who discovered edoxaban, is committed to expanding scientific knowledge about this DOAC, as demonstrated through research programmes evaluating its use in a broad range of cardiovascular conditions, patient types and clinical settings in atrial fibrillation (AF) and venous thromboembolism (VTE) designed to further build on the results of the pivotal ENGAGE-AF and Hokusai-VTE studies. More than 100,000 patients worldwide are expected to participate in the Edoxaban Clinical Research Programme, which is comprised of more than 10 RCTs (randomised, controlled trials), registries and non-randomised clinical studies, including completed, ongoing and future research. Our goal is to generate new edoxaban clinical and real-world-data regarding its use in AF and VTE populations, providing physicians and patients worldwide with greater treatment assurance.

SOURCE Servier Canada Inc.

Crohn's and Colitis Canada Announces Updated Position Statement on Biosimilar Drugs

TORONTO, Sept. 5, 2019  /CNW/ - Today, Crohn's and Colitis Canada released their updated Position on biosimilar drugs. Supporting studies, including a report on cross-Canada surveys of patients and caregivers, gastroenterologists and inflammatory bowel disease (IBD) nurses was also released.

"Crohn's and Colitis Canada is a research-based organization. We took the time to carefully review our position on biosimilars and particularly on related non-medical switching policy in order to represent our patients thoughtfully and responsibly," says Mina Mawani, President and CEO of Crohn's and Colitis Canada. "Our position that a non-medical switch policy is not in the best interest of patients is based on what we've learned these past few months. We are very pleased to share our updated Position and the studies we've developed to help inform policy across Canada."

The Crohn's and Colitis Canada Position Statement asserts that:

• Biosimilars are a safe and effective treatment for people with Crohn's disease and ulcerative colitis (the two main forms of IBD). 
• The decision to switch a patient from a biologic drug to its biosimilar should be based on patient/doctor choice. 
• Non-medical switching from a biologic drug to its biosimilar is not in the best interest of patients.

The Position Statement offers details on factors that must be considered in the event of the implementation of a non-medical switch policy including critical patient exemptions, required patient supports, extraordinary monitoring requirements and significant communication and education needs. "We have serious concerns about the potential for multiple non-medical switching – this cannot be supported," says Ms. Mawani. "Further, we understand that such policies are being considered because of fiscal pressures, so should the price differential between biologics and biosimilars be eliminated, a non-medical switch should not be considered by policy-makers at all."

Canada has one of the highest rates of Crohn's and colitis in the world. Today, more than 270,000 Canadians have Crohn's and colitis, a number that is expected to increase to over 400,000 within the next decade. Alarmingly, this chronic autoimmune disease is increasingly being diagnosed in children and as our population ages, a new challenge of caring for the frail elderly with IBD will present itself. Crohn's and colitis prevalence is also increasing amongst Canada's immigrant population.

Crohn's and Colitis Canada is committed to supporting people with IBD from across the country and will continue to share information with health care decision makers in all provinces and territories to inform patient-centred policy. "Our focus is on the patient. Their health and well-being is our priority," says Ms. Mawani.

Resources:

• Updated Crohn's and Colitis Canada Biosimilars Position Statement
• Patient and Health Care Provider Input: Non-Medical Biosimilar Switch Policy for Patients with Inflammatory Bowel Disease 
  • Comprehensive Report
  • Summary and Key Findings
• Impact of Inflammatory Bowel Disease in Canada Report

ABOUT CROHN'S AND COLITIS CANADA 
Crohn's and Colitis Canada is the only national, volunteer-based charity focused on finding the cures for Crohn's disease and ulcerative colitis and improving the lives of everyone impacted by these diseases. We are the world's second largest health charity funder of Crohn's and colitis research, and our patient programs and advocacy efforts support the people affected by these chronic autoimmune diseases, which cause the body to attack healthy tissue, leading to the inflammation of all or part of the gastrointestinal tract. Visit crohnsandcolitis.ca for more information.

SOURCE Crohn's and Colitis Canada

How Common are Mental Health Problems in Arthritis Patients? Research Reveals Flaw in Determining Extent of Problem

VANCOUVER, Sept. 5, 2019 /CNW/ - A recent Arthritis Research Canada study has revealed that while administrative health databases are increasingly being used to study mental health in rheumatic diseases, researchers have used different ways to identify patients who have depression and anxiety, making it challenging to draw conclusions and comparisons across publications. 

Administrative health databases refer to secondary data collected for billing purposes, which may be comprised of several unique administrative data sources – such as those capturing inpatient visits, outpatient visits, and prescription claims. These databases are increasingly used to study depression and anxiety in rheumatic diseases, but they only record details of those who seek and receive treatment. And mental health problems are notoriously under-reported.

"We identified the differing methods used to evaluate depression and anxiety in 36 studies using administrative health data and recommend examining multiple administrative data sources to understand the extent of mental health problems in populations living with arthritis," said Alyssa Howren, an Arthritis Research Canada trainee and the study's lead researcher.  

While there are many physical complications associated with rheumatic diseases, there is also an increased risk of depression and anxiety. A recent Canadian population-based study reported that individuals with rheumatoid arthritis have a 1.5-fold increased risk for incident depression and a 1.2-fold increased risk for incident anxiety. 

"Mental illnesses can lead to increased disease activity, suboptimal treatment adherence, reduced treatment response and an overall decreased quality of life" Howren said. 

While administrative health data are very accessible and reduce common biases associated with hospital- and clinic-based studies, there are many challenges associated with relying on it to identify depression and anxiety. This research is important because it is a first step for researchers at Arthritis Research Canada towards understanding mental health issues in individuals living with arthritis using administrative health data.

To read the abstract of this paper in Arthritis Care & Research, please click here. 

To access a full copy of the paper, please contact:

Mary De Vera
Research Scientist of Pharmacoepidemiology, MSc, PhD
mdevera@arthritisresearch.ca

Alyssa Howren
Arthritis Research Canada Trainee, BSc, MSc, PhD Student
alyssa.howren@ubc.ca 

ABOUT ARTHRITIS RESEARCH CANADA

Arthritis Research Canada is the largest clinical arthritis research centre in North America. Our mission is to transform the lives of people living with arthritis through research and engagement. Led by world-renowned rheumatologist, Dr. John Esdaile, Arthritis Research Canada's scientific team of over 100 are creating a future where people living with arthritis are empowered to triumph over pain and disability. Within British Columbia, Alberta and Quebec, Arthritis Research Canada is leading research aimed at arthritis prevention, early diagnosis and treatment, and quality of life issues.

SOURCE Arthritis Research Canada

Fighting frostbite: focusing on prevention and early drug treatment are the keys to success

The Physiological Society – Press release

For immediate release – 3 September 2019

Frostbite is an injury which usually affects the extremities,  such as fingers and toes, and has the potential of causing irreversible tissue loss. The treatment of freezing cold injuries to the periphery has advanced substantially in the last 10 years. Optimal outcomes are only likely to be achieved if a multi-disciplinary team uses the full range of diagnostic and treatment approaches that are now available, said Chris Imray, CASE Medicine, presenting this week at the Extreme Environmental Physiology conference of The Physiological Society.

The internet, and satellite phones, with digital images allow immediate access by patients from remote geographical locations to hospital-based specialists who can assess cold injuries and advise on early field-care.

The severity of frostbite injuries can now be assessed with a bone scan called triple-phase, allowing early prediction of likely subsequent tissue loss. Newer thrombolytic therapies (which dissolve blood clots) such as iloprost have transformed treatment options when instigated at an early time-point.

Frostbite occurs when the fluid in our cells freezes, it swells and chemicals are produced. These two processes permanently damage the tissues in our bodies. Frostbite can vary in the depth and the extent of damage it causes.

If only superficial skin is damaged and it is rewarmed soon after injury it may recover completely, this is called frost-nip. Frostbite commonly occurs on the extremities such as fingers, toes, ears, penis and nose, but it can technically occur anywhere.

It obviously requires a cold, but not necessarily freezing, environment and wind-chill can add to the potential for damage. Frostbite is more likely at altitude (less oxygen is available for the tissues to recover) and in a hypothermic or injured person. It is more likely if circulation is restricted by tight fitting clothes, boots or jewellery.

Clients with pre-existing conditions which may predispose to poor circulation (e.g. diabetes, Raynaud's sufferers etc.) are more likely to suffer from frostbite. Certain drugs that effect peripheral circulation may also predispose people (e.g. beta blockers or nicotine in cigarettes).

Addressing the importance of the issue, Chris Imray said:

“Awareness and experience is the key to prevention, and prevention is the key to treatment. The adage that “prevention is better than treatment” is especially true for frostbite, which is typically preventable but very difficult to treat.”

ProMIS Neurosciences to Present at HC Wainwright Investment Conference

Company to showcase its innovative Alzheimer's, Parkinson's and ALS programs

TORONTO and CAMBRIDGE, MA, Sept. 3, 2019 /CNW/ - ProMIS Neurosciences, Inc. (TSX: PMN) (OTCQB: ARFXF), a biotechnology company focused on the discovery and development of antibody therapeutics targeting toxic oligomers implicated in the development of neurodegenerative diseases, today announced its participation in the 21^st Annual Global Investment Conference sponsored by H.C. Wainwright & Co. LLC.  The conference is being held September 8-10, 2019 at the New York Palace Hotel in New York.

ProMIS' Executive Chairman, Eugene Williams will provide overviews of its novel drug discovery and development programs for Alzheimer's disease, Parkinson's disease and ALS  (amyotrophic lateral sclerosis) Tuesday, September 10^th at 10:25 am ET.  The audio webcast and slides of Mr. Williams' presentation will be archived and available on ProMIS' web site and through the following link http://wsw.com/webcast/hcw5/arfxf/. 

About ProMIS' Platform Technology
Numerous studies show that a common root cause of neurodegenerative diseases is the toxic oligomer, a misfolded protein that derives from naturally occurring proteins in the brain. Using its novel drug discovery platform, ProMIS can uniquely and selectively target the toxic oligomer, filling a critical gap for drug developers as traditional approaches to developing antibodies are unable to isolate and target the toxic oligomer with adequate precision. This proprietary platform can identify targets to produce, test and advance antibody candidates quickly and cost-effectively. ProMIS' lead candidate antibody, PMN310 for Alzheimer's disease (AD), demonstrates a high degree of binding to toxic oligomers without binding to non-toxic forms of naturally occurring amyloid beta protein. The company's program for Parkinson's disease (PD) is based on the development of several potential antibody therapeutic candidates aimed at selectively targeting toxic oligomers of the protein α-synuclein, considered a root cause of PD. Similarly, ProMIS has identified antibody candidates selectively targeting toxic oligomers of the protein TDP43, considered a root cause of ALS.

About ProMIS Neurosciences
ProMIS Neurosciences, Inc. is a development stage biotechnology company focused on discovering and developing antibody therapeutics selectively targeting toxic oligomers implicated in the development and progression of neurodegenerative diseases, in particular Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). The Company's proprietary target discovery platform is based on the use of two complementary thermodynamic, computational discovery engines - ProMIS and Collective Coordinates - to predict novel targets known as Disease Specific Epitopes on the molecular surface of misfolded proteins. Using this unique precision approach, the Company is developing novel antibody therapeutics for AD, ALS and PD. ProMIS is headquartered in Toronto, Ontario, with offices in Cambridge, Massachusetts. ProMIS is listed on the Toronto Stock Exchange under the symbol PMN, and on the OTCQB Venture Market under the symbol ARFXF.

To learn more, visit us at www.promisneurosciences.com, follow us on Twitter and LinkedIn and listen to the podcast, Saving Minds, at iTunes or Spotify.

The TSX has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. This information release contains certain forward-looking information. Such information involves known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from those implied by statements herein, and therefore these statements should not be read as guarantees of future performance or results. All forward-looking statements are based on the Company's current beliefs as well as assumptions made by and information currently available to it as well as other factors. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Due to risks and uncertainties, including the risks and uncertainties identified by the Company in its public securities filings, actual events may differ materially from current expectations. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

SOURCE ProMIS Neurosciences Inc.

Servier Canada announces Positive Results of the ENTRUST-AF PCI Study of LIXIANA® (edoxaban) in Patients with Atrial Fibrillation

• ENTRUST-AF PCI study achieved the primary safety endpoint of non-inferiority in bleeding for edoxaban-based dual therapy compared with VKA-based triple antithrombotic therapy (using a risk-based duration of ASA for at least one month) in AF patients following stent placement
• Data presented during ESC Congress 2019 Hot Line Session and simultaneously  published in The Lancet 

LAVAL, QC, Sept. 3, 2019 /CNW Telbec/ - Today, Servier Canada announces results from ENTRUST-AF PCI (n=1,506), the first large randomised study to evaluate the efficacy and safety of once-daily edoxaban (brand name as LIXIANA^®) plus a P2Y12 inhibitor (antiplatelet agents) against a regimen of vitamin K antagonist (VKA) plus P2Y12 inhibitor and acetyl salicylic acid (ASA) in atrial fibrillation (AF) patients following successful percutaneous coronary intervention (PCI). The study showed the edoxaban-based regimen is non-inferior compared with the VKA-based triple therapy regimen on the composite endpoint of major or clinically-relevant non-major bleeding over 12 months.^1,2 The results were presented in a late-breaking presentation during the Hot Line Session today at ESC Congress 2019  in Paris, France and published in The Lancet.

It is estimated that about 20% to 40% of patients with AF also present with coronary artery disease (CAD), a sizeable proportion of whom require revascularization using percutaneous coronary intervention (PCI) and stent implantation.³ VKA-based triple therapy including a P2Y12 inhibitor and ASA used to be the treatment of choice for these patients, however, triple therapy has been associated with significantly increased risk of bleeding.⁴ENTRUST-AF PCI was a multinational, multicenter, randomised, open-label, blinded outcome evaluation Phase 3b study that evaluated a 12-month antithrombotic regimen of edoxaban 60 mg once-daily in combination with a P2Y12 inhibitor compared to a VKA in combination with a P2Y12 inhibitor and 100 mg of ASA for a risk adapted duration for one to 12 months in patients with AF following successful stent placement for ACS or stable CAD. The primary safety outcome was the composite of major or clinically relevant non-major bleeding, as defined by the International Society of Thrombosis and Haemostasis.¹

"Since about one of five patients with AF may require PCI over time, clinicians need data about the safety of the anticoagulant therapy options for stroke prevention when such event occurs. The ENTRUST-AF PCI trial shows today that the combination of edoxaban 60 mg daily in combination with a P2Y12 inhibitor is safe compared to the VKA-based triple therapy in patients with AF post-PCI." Said Dr. Jean-Francois Tanguay,   Professor of medicine,  Desgroseillers-Bérard Research Chair in interventional cardiology, Université de Montréal and Director of the Interventional Cardiology Division at the Montreal Heart Institute.

The ENTRUST-AF PCI study enrolled 1,506 patients with AF following successful stent placement for ACS (51.6%) or stable CAD (48.4%). Patients were randomised to receive once-daily edoxaban (60 mg or 30 mg per dose reduction criteria) plus a P2Y12 inhibitor for 12 months or a VKA in combination with a P2Y12 inhibitor plus 100 mg of ASA. Major or clinically relevant non-major bleeding, the study's primary endpoint, occurred in 128 (17.0%; annualised: 20.7%) patients in the edoxaban group and 152 (20.1%; annualised: 25.6%) patients in the VKA group (HR: 0.83, 95% CI: 0.654-1.047), demonstrating non-inferiority of the edoxaban-based dual therapy for the 12 months post PCI (p=0.001, pre-specific non-inferiority margin=1.2). There was a trend toward less bleeding with edoxaban, though, results did not show statistical superiority (p=0.115).¹ Similar rates of the main efficacy composite outcome of cardiovascular death, stroke, systemic embolic events, spontaneous myocardial infarction, and definite stent thrombosis were observed for the edoxaban-based dual therapy regimen and the VKA-based triple therapy regimen. 

In the ENTRUST-AF PCI study, bleeding events were consistent across all commonly applied bleeding definitions (ISTH, TIMI, BARC). Intracranial hemorrhage occurred in four (0.58% per year) of edoxaban-treated patients and nine (1.32% per year) VKA-treated patients. Fatal bleeding occurred in one patient receiving edoxaban and seven patients receiving VKA treatment. 

"Lixiana^® (edoxaban) is the latest direct oral anticoagulant marketed in Canada, and it is now publicly reimbursed in almost all provinces. These results reinforce the  safety profile of  Lixiana^® in different sub-types of patients suffering from AF, in this case, patients undergoing a successful PCI. Another recent sub- analysis of the 1-Year data of ETNA-AF, the largest and most comprehensive repository of data on the use of DOAC's in real life, confirmed the safety profile of LIXIANA in the elderly/very elderly AF patients " said Frederic Fasano, CEO of Servier Canada.

ENTRUST-AF PCI is one of more than 10 randomised, controlled trials (RCTs), registries and non-randomised clinical studies that comprise the Edoxaban Clinical Research Programme, EDOSURE. More than 100,000 patients worldwide are expected to participate in EDOSURE studies, with the goal of generating new clinical and real-world data regarding edoxaban use in AF and venous thromboembolism populations, providing physicians and patients worldwide with greater treatment confidence.

About ENTRUST-AF PCI
EdoxabaN TReatment VersUS Vitamin K Antagonist in PaTients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention (ENTRUST-AF- PCI) is a prospective, multinational, multicenter, randomised, open-label with blinded endpoint evaluation phase 3b study.  The ENTRUST-AF PCI trial was designed to evaluate the safety and accrue exploratory information on the efficacy of an edoxaban-based antithrombotic regimen compared to a VKA-based antithrombotic regimen in patients with AF following successful PCI with stent implantation. The primary objective of the ENTRUST-AF PCI trial was to compare the incidence of major or clinically relevant non-major International Society on Thrombosis and Haemostasis (ISTH)-defined bleeding over a 12-month period of an edoxaban-based antithrombotic regimen against a VKA-based regimen. 1,506 patients were enrolled in ENTRUST-AF PCI from 186 clinical sites across Europe and Asia. Participants were randomly allocated in a 1:1 ratio to a 12-month antithrombotic regimen of edoxaban and a P2Y12 inhibitor or to a standard therapy with a vitamin K antagonist (VKA) and P2Y12 inhibitor plus ASA for one to 12 months.¹

About Atrial Fibrillation

AF is a condition where the heart beats irregularly and rapidly. When this happens, blood can pool and thicken in the chambers of the heart causing an increased risk of blood clots. These blood clots can break off and travel through the blood stream to the brain (or sometimes to another part of the body), where they have the potential to cause a stroke.⁵

AF is the most common type of heart rhythm disorder affecting approximately 350,000 Canadians⁶ and is associated with substantial morbidity and mortality.⁷ Compared to those without AF, people with the arrhythmia have a 3-5 times higher risk of stroke.⁹ One in five of all strokes are a result of AF.⁸

About Edoxaban

Edoxaban is an oral, once-daily, direct factor Xa (pronounced "Ten A") inhibitor. Factor Xa is one of the key components responsible for blood clotting, so inhibiting this makes the blood thin and less prone to clotting. Edoxaban was discovered and developed by Daiichi Sankyo Co., Ltd. On June 27, 2016, Daiichi Sankyo and Servier Canada entered into an agreement whereby Servier Canada would market the oral, once-daily anticoagulant edoxaban in Canada, upon approval by the Canadian health authority. Edoxaban is currently marketed in more than 30 countries and regions around the world.

About Servier Canada 

Servier Canada is an affiliate of the independent French Servier Group governed by a Private Foundation. We, at Servier, are committed to therapeutic progress to serve patient needs. We work assiduously to provide the Canadian medical community and its patients with innovative therapeutic solutions. As such, Servier Canada is partnering with various players in the life science ecosystem including researchers, clinicians, entrepreneurs and innovators. In addition to these research partners, the International Center for Therapeutic Research (ICTR) located in Laval, is dedicated to preclinical and clinical development with more than 50 studies conducted throughout Canada over the last 10 years. More information is available at www.servier.ca

About EDOSURE – Edoxaban Clinical Research Programme
More than 10 studies, more than 100,000 patients worldwide

Daiichi Sankyo, who discovered Edoxaban, is committed to expanding scientific knowledge about this DOAC, as demonstrated through research programmes evaluating its use in a broad range of cardiovascular conditions, patient types and clinical settings in atrial fibrillation (AF) and venous thromboembolism (VTE) designed to further build on the results of the pivotal ENGAGE-AF and Hokusai-VTE studies. More than 100,000 patients worldwide are expected to participate in the edoxaban clinical research programme, EDOSURE, which is comprised of more than 10 RCTs (randomised, controlled trials), registries and non-randomised clinical studies, including completed, ongoing and future research. Our goal is to generate new edoxaban clinical and real-world-data regarding its use in AF and VTE populations, providing physicians and patients worldwide with greater treatment assurance.

SOURCE Servier Canada Inc.

Avicanna (TSX: AVCN) Further Strengthens its Position as a Canadian Leader in Cannabinoid Based Research and Development with Expansion of University of Toronto Collaboration and Execution of University of Guelph Research Agreement

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TORONTO, Aug. 30, 2019 /CNW/ - Avicanna Inc. ("Avicanna" or the "Company") (TSX: AVCN) a biopharmaceutical company focused on the development, manufacturing and commercialization of plant-derived cannabinoid-based products is pleased to announce that it has expanded the scope and duration of its research and collaboration agreement with Dr. Christine Allen's research group at the University of Toronto. Additionally, Dr. Allen has stepped down as Avicanna's Chief Scientific Officer, having accepted a prominent role with the University of Toronto, however, Dr. Allen will increase her involvement in Avicanna's pharmaceutical development and optimization through the expanded collaboration between Avicanna and Dr. Allen's research group. Avicanna further announces that it has entered into a research agreement with the University of Guelph. The total amount that the Company expects to spend on its research and development activities in connection with these agreements is approximately as follows: (i) $257,000 in 2019; (ii) $410,000 in 2020; (iii) $395,000 in 2021 and (iv) $198,000 in 2022.

University of Toronto

Avicanna has amended its sponsored research and collaboration agreement with the University of Toronto to extend its partnership with Dr. Christine Allen's research group to November 2022. The expanded scope of the sponsored research and collaboration agreement outlines several projects including the characterization and pre-clinical analysis of Avicanna's pipeline of phyto-therapeutic & pharmaceutical products and the development of other pharmaceutical dosage forms including sustained release formulations. Additional projects under the research and collaboration agreement include analysis of the safety, efficacy and potential synergies of cannabinoids and other therapeutic agents.

Additionally, Avicanna will collaborate with the University of Toronto to design and develop advanced nanoparticle and microparticle-based pharmaceutical formulations comprised of cannabinoid/terpene-based therapies with a specific focus on applications in cancer, osteoarthritis and inflammatory bowel disease.

In addition, Dr. Allen has accepted a role as Associate Vice-President & Vice-Provost, Strategic Initiatives at the University of Toronto. In connection with her appointment, Dr. Allen has stepped down as the Company's Chief Scientific Officer but will continue to lead Avicanna's pharmaceutical development efforts through the extended research & collaboration agreement.

Dr. Justin Grant, Avicanna's Executive Vice-President of Scientific Affairs added "The scientific rigor and advanced drug delivery research in Dr. Christine Allen's laboratory aligns with Avicanna's goal to develop safe, high quality and effective cannabis-based pharmaceutical products tailored for specific symptoms and indications."

"I would like to take this opportunity to thank Dr. Christine Allen for her leadership in the establishment of our research and development practices, which now extend globally across four active laboratories, and the completion of several product categories including derma-cosmetics, phyto-therapeutic and specific pharmaceuticals. As we proceed to the next stage, which is commercialization, we are grateful to have Dr. Allen's continued support in development of the more advanced pharmaceutical products where she is a world-renowned expert."  said Aras Azadian, Chief Executive Officer of Avicanna. 

Dr. Allen commented, "My laboratory is delighted to continue to work with Avicanna and remains committed to the evidence-based development of advanced dosage forms of cannabinoids with targeted safety and efficacy profiles."

University of Guelph

Avicanna has entered into a research agreement (the "Research Agreement") with the University of Guelph for a project to be performed by Dr. Max Jones, Associate Professor, Department of Plant Agriculture, as principal investigator. Dr. Jones has been involved in the development of Avicanna's long term genetics and breeding program over the past six (6) months. The program is focused on the stabilization of unique commercial strains, long term selective breeding programs to develop genetics with increased efficiency and also increased expression and characterization of rare cannabinoids. The project to be performed under the Research Agreement is expected to provide genetic analysis of Avicanna's cultivars to provide a genetic "fingerprint" for each cultivar and determine their relative relationships (i.e. genetic distance) to one another. Additionally, Dr. Jones' group is hopeful to produce polyploid plants for Avicanna's breeding program and establish and optimize tissue culture and micropropagation methods that can be utilized in Avicanna's cultivation sites in Colombia. All research data and research reports created under the Research Agreement will remain the sole property of Avicanna, however, Avicanna has granted a license to the University of Guelph to use such reports and data for research and academic purposes. The study is expected to be completed in two (2) phases and will continue for a period of one (1) year from the date the University of Guelph obtains a permit from Health Canada to import certain plant material from the Company's subsidiaries in Colombia. The cost of the study is expected to be approximately $59,360.

Aras Azadian, the Company's Chief Executive Officer, stated "As a leading company focused on research and development and intellectual property development in the cannabinoid industry, we believe it is imperative to have this evidence-based philosophy in all of our business units including our cultivation projects, and its genetics and seed programs. With this collaboration we aim to ensure that Avicanna is prepared for the future of this emerging industry by staying ahead of the curve through our advanced genetic development and breeding programs."

About Avicanna

Avicanna is an Ontario corporation focused on the development, manufacturing and commercialization of plant-derived cannabinoid-based products through its two main business segments, cultivation and research and development.

Avicanna's two majority-owned subsidiaries, Sativa Nativa S.A.S. and Santa Marta Golden Hemp S.A.S., both located in Santa Marta, Colombia are the base for Avicanna's cultivation activities. These two companies are licensed to cultivate and process cannabis for the production of cannabis extracts and purified cannabinoids including cannabidiol (CBD) and tetrahydrocannabinol (THC). 

Avicanna's research and development business is primarily conducted out of Canada at its headquarters in the Johnson & Johnson Innovation Centre, JLABS @ Toronto. Avicanna's scientific team develops products, and Avicanna has also engaged the services of researchers at the Leslie Dan Faculty of Pharmacy at the University of Toronto for the purpose of optimizing and improving upon its products. 

Avicanna's research and development and cultivation activities are focused on the development of its key products, including plant-derived cannabinoid pharmaceuticals, phyto-therapeutics, derma-cosmetics and Extracts (defined as plant-derived cannabinoid extracts and purified cannabinoids, including distillates and isolates), with a goal of eventually having these products manufactured and distributed through various markets.

Stay Connected

For more information about Avicanna, visit www.avicanna.com, call 1-647-243-5283, or contact Setu Purohit, President by email info@avicanna.com.

Cautionary Note Regarding Forward-Looking Information and Statements

Certain information in this press release contains forward-looking statements. Such statements include but are not limited to the intended outcomes of the studies to be conducted under the research and collaboration agreement with the University of Toronto and the expected outcomes of the studies to be conducted under the Research Agreement. This information is based on current expectations that are subject to significant risks and uncertainties that are difficult to predict, including the risk factors set out under the heading "Risk Factors" in the Company's long form final prospectus dated July 8, 2019. Actual results might differ materially from results suggested in any forward-looking statements. The Company assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those reflected in the forward-looking statements, unless and until required by securities laws applicable to the Company.

SOURCE Avicanna Inc.