Category Archives: Clinical Research

JSM could lead to improved arthritis treatment

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An algorithm to monitor the joints of patients with arthritis, which could change the way that the severity of the condition is assessed.

An algorithm to monitor the joints of patients with arthritis, which could change the way that the severity of the condition is assessed, has been developed by a team of engineers, physicians and radiologists led by the University of Cambridge.

The technique, which detects tiny changes in arthritic joints, could enable greater understanding of how osteoarthritis develops and allow the effectiveness of new treatments to be assessed more accurately, without the need for invasive tissue sampling.

Osteoarthritis is the most common form of arthritis in the UK. It develops when the articular cartilage that coats the ends of bones and allows them to glide smoothly over each other at joints, is worn down, resulting in painful, immobile joints. Currently, there is no recognised cure and the only definitive treatment is surgery for artificial joint replacement.

Osteoarthritis is normally identified on an x-ray by a narrowing of the space between the bones of the joint due to a loss of cartilage. However, x-rays do not have enough sensitivity to detect subtle changes in the joint over time.

Joint space in hip, knee and ankle joints as analyzed by the JSM algorithm. – Tom Turmezei

 

“In addition to their lack of sensitivity, two-dimensional x-rays rely on humans to interpret them,” said lead author Dr Tom Turmezei from Cambridge’s Department of Engineering. “Our ability to detect structural changes to identify disease early, monitor progression and predict treatment response is frustratingly limited by this.”

The technique developed by Dr Turmezei and his colleagues uses images from a standard computerised tomography (CT) scan, which isn’t normally used to monitor joints but produces detailed images in three dimensions.

The semi-automated technique, called joint space mapping (JSM), analyses the CT images to identify changes in the space between the bones of the joint in question, a recognised surrogate marker for osteoarthritis. After developing the algorithm with tests on human hip joints from bodies that had been donated for medical research, they found that it exceeded the current ‘gold standard’ of joint imaging with x-rays in terms of sensitivity, showing that it was at least twice as good at detecting small structural changes. Colour-coded images produced using the JSM algorithm illustrate the parts of the joint where the space between bones is wider or narrower.

“Using this technique, we’ll hopefully be able to identify osteoarthritis earlier, and look at potential treatments before it becomes debilitating,” said Dr Turmezei, who is now a consultant at the Norfolk and Norwich University Hospital’s Department of Radiology. “It could be used to screen at-risk populations, such as those with known arthritis, previous joint injury, or elite athletes who are at risk of developing arthritis due to the continued strain placed on their joints.”

While CT scanning is regularly used in the clinic to diagnose and monitor a range of health conditions, CT of joints has not yet been approved for use in research trials. According to the researchers, the success of the JSM algorithm demonstrates that 3D imaging techniques have the potential to be more effective than 2D imaging. In addition, CT can now be used with very low doses of radiation, meaning that it can be safely used more frequently for the purposes of ongoing monitoring.

“We’ve shown that this technique could be a valuable tool for the analysis of arthritis, in both clinical and research settings,” said Dr Turmezei. “When combined with 3D statistical analysis, it could be also be used to speed up the development of new treatments.”

The results are published in the journal Scientific Reports.

SOURCE: www.europeanpharmaceuticalreview.com/news/76547

Roche SMA drug shines in study as costly new therapies advance

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A drug being co-developed by Roche to treat spinal muscular atrophy (SMA) helped improve development scores in babies with the genetic disease, a study released on Monday showed, as the race heats up for therapies destined to be among the drug industry’s most expensive.

PTC Therapeutics, which struck a licensing deal with Roche in 2011 for its SMA program, said more than 90 percent of babies with severe Type 1 SMA given the RG7916 drug achieved a greater than four-point increase in a test to measure their neuromuscular progress six months after treatment began.

PTC shares, which are listed on the Nasdaq, rose as much as 30 percent.

The companies hope their medicine, also known as risdiplam, will be approved to take on rival drug Spinraza from Biogen, which sells for $750,000 for the first year of therapy and about $375,000 annually after that.

Novartis is also quickly advancing in the SMA field with its $8.7 billion acquisition this year of U.S.-based Avexis that is working on a gene therapy for the disorder.

Analysts from Barclays project Novartis’s one-time treatment could run to $1.25 million per patient.

“We are delighted that up to 6.5-fold increase of protein production has translated into clinical impact for these babies,” PTC Chief Executive Stuart Peltz said in a statement about the RG7916 study, adding no babies required a tracheostomy or permanent ventilation since the study began, and no baby lost his or her ability to swallow.

SMA is an often-deadly genetic neuromuscular disorder caused by a missing or defective gene that normally produces a protein needed for development of motor neurons in the spinal cord. This leads to muscle wasting. Many babies with the severest form of the disorder die, while others never stand or walk.

Barclays analyst Emmanuel Papadakis expects that if Roche and PTC’s data holds up on RG7916 with regulators, it could become a fierce competitor to Spinraza, now the only licensed SMA therapy.

Cowen analysts also said on Monday they view PTC’s update as very encouraging for approval — and for competitiveness versus Spinraza, which is administered into the spine about four times a year. Roche’s and PTC’s drug is taken orally.

Novartis Chief Executive Vas Narasimhan also has high hopes for his own newly acquired SMA treatment, saying in April after the Swiss company bought Avexis that its gene therapy has “multi-billion dollar peak sales potential”.

SOURCE: www.pmlive.com/pharma_news

AbbVie trial backs chemo-free Imbruvica combo regimen

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The pairing of of AbbVie’s Imbruvica and Roche’s Gazyva has hit the mark in a chronic lymphocytic leukaemia trial – raising the prospect of a new chemotherapy-free combination regimen for previously untreated CLL patients.

The iLLUMINATE trial showed that oral BTK inhibitor Imbruvica (ibrutinib) plus anti-CD20 injection Gazyva (obinutuzumab) was more effective than Gazyva plus chemo (chlorambucil) in treatment-naïve, older patents (aged 65 or more) with either CLL or small lymphocytic leukaemia (SLL) – a different form of the same disease.

The top-line data isn’t being made available just yet, but in a statement AbbVie said the duo extended progression-free survival (PFS) compared to the active control arm, adding that it will be sharing the data with regulators, in the hope of bringing “the first chemotherapy-free CD20 combination in first-line CLL treatment” to market.

The trial ties in with AbbVie’s strategy of expanding use of Imbruvica as a first-line CLL treatment and, while Gazyva has been something of a slow burner for Roche since its launch in that setting in 2014, it has started to gain momentum with sales rising 41% to CHF 278m last year.

The combination of Gazyva and chlorambucil is now recommended as a first-line therapy for CLL by the US National Comprehensive Cancer Network, which deems it a category 1 treatment, ie one with a high level of evidence backing its use, so outperforming it is a big win for the combination.

“This chemotherapy-free combination represents a potential new treatment option for patients with CLL,” said John Gribben of Barts Cancer Institute in the UK, the lead investigator for the iLLUMINATE study.

“It’s exciting to see the blood cancer treatment paradigm continue to evolve – each advance moves us one step closer to a better standard of care for these patients,” he added.

Imbruvica is already approved for all lines of therapy in CLL, and beating out chlorambucil is not a big surprise as AbbVie’s drug comprehensively outperformed the chemotherapy as a monotherapy in the head-to-head RESONATE-2 trial.

The trial was the basis of Imbruvica’s approval in 2016 as a chemo alternative in treatment-naïve CLL, and the disease accounts for the lion’s share of the drug’s sales, which grew almost 39% to $762m in the first quarter of this year, topping estimates. AbbVie is predicting sales of $3.3bn this year, well on course for its peak sales target of $6bn-$7bn.

AbbVie’s head of R&D Michael Severino said on the company’s first-quarter results call that the strategy is to build a “body of evidence” for Imbruvica – both as a monotherapy and in combination – across different CLL segments “including young and fit patients and the watch-and-wait population”.

SOURCE: www.pmlive.com/pharma_news

Eczema drug effective against severe asthma

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Two new studies of patients with difficult-to-control asthma show that the eczema drug dupilumab alleviates asthma symptoms and improves patients’ ability to breathe better than standard therapies.

Two new studies of patients with difficult-to-control asthma show that the eczema drug dupilumab alleviates asthma symptoms and improves patients’ ability to breathe better than standard therapies. Dupilumab, an injectable anti-inflammatory drug, was approved in 2017 by the Food and Drug Administration as a treatment for eczema, a chronic skin disease.

The more than 2,000 patients enrolled in the studies suffered from moderate to severe asthma. All used standard asthma inhalers, and some also took oral steroids to control their severe asthma symptoms.

In one study, the rate of asthma exacerbations was almost cut in half for those taking dupilumab compared with those taking a placebo. On average, patients taking a placebo had close to one exacerbation per day during the year of the study. Exacerbations are periods of sudden worsening of asthma symptoms such as wheezing, coughing, shortness of breath and tightness in the chest.

Although the drug significantly reduced asthma symptoms for all patients, dupilumab worked particularly well in patients with high numbers of a specific type of white blood cell, called eosinophils, circulating in the bloodstream. For those patients, asthma exacerbations were cut by two-thirds.

“This drug not only reduced severe symptoms of asthma, it improved the ability to breathe,” said Dr Mario Castro, the Alan A. and Edith L. Wolff Distinguished Professor of Pulmonology and Critical Care Medicine. “That’s important because these patients have a chronic disabling disease that worsens over time with the loss of lung function. So far, we do not have a drug for asthma that changes the course of the disease. Current drugs for severe asthma help reduce trips to the emergency room, for example, but they don’t improve lung function.”

The first study included about 1,900 patients of at least 12 years of age and with moderate to severe asthma requiring they use at least three different inhalers to control their symptoms. One inhaler contained a corticosteroid that reduces inflammation, another contained a long-acting bronchodilator that relaxes airway muscles, and the third was a “rescue” inhaler filled with albuterol, a short-acting bronchodilator that quickly opens up the airway in the event of a more severe asthma attack.

Patients taking these inhaled medications then were randomly assigned to receive either dupilumab or a placebo for one year. Patients receiving dupilumab — an injectable antibody — also were randomly assigned to a higher or lower dose of the drug. Neither patients nor their doctors knew whether they were receiving the drug or the placebo.

In addition to reduced symptoms, the patients receiving dupilumab showed improved lung function in a test of “forced expiratory volume.” This test measures the amount of air a person can force from the lungs during a deep exhale. Patients receiving dupilumab, regardless of dose, improved their lung function by approximately 130-200 millilitres greater than those receiving the placebo. In general, there were no significant differences between the patients receiving high and low doses of dupilumab.

Rates of emergency room (ER) visits and hospitalisations also were improved for patients receiving the drug. In the placebo group (with 638 patients), on average, 6.5 percent of the patients required an emergency room visit or hospitalisation due to asthma during the study. In the dupilumab group (with 1,264 patients), on average, 3.5 percent of patients needed emergency care or hospitalisation due to asthma.

Based on the second study, Dr Castro said another benefit of the drug could be the ability to wean severe asthma patients off of chronic oral steroids, which can cause debilitating long-term side effects, including stunted growth, diabetes, cataracts and osteoporosis. The second study included about 200 patients using the same inhaled asthma medications as patients in the larger trial, plus additional oral steroids — usually prednisone — to control their more severe symptoms. Half of the patients receiving dupilumab in this study were able to completely eliminate prednisone use. And 80 percent of dupilumab-treated patients were able to at least cut their doses in half. Patients on placebo also reduced prednisone use but to a lesser degree, likely because the protocols of participating in a clinical trial help asthma control generally.

Dr Castro said doctors would like to help patients rely less on steroids for asthma control because those with severe asthma can be forced to take these drugs for decades to enable them to breathe.

“I have patients who have had to stop working and go on disability because their asthma symptoms are so severe they can no longer function in the workplace,” Dr Castro said. “I’m excited about the potential of dupilumab because I have so many patients who have maxed out on available therapies and they still can’t breathe. It can become a very disabling disease.”

Patients receiving dupilumab did experience known side effects of the drug, including pain and swelling at the injection site and a short-term bump in the number of eosinophil cells in the blood. Five patients who received dupilumab and three patients who received placebo died during the study period. According to the investigators and descriptions of these patients’ medical histories, all suffered from multiple severe medical conditions, and none of the deaths was deemed related to the study protocol.

The studies will be published online in The New England Journal of Medicine.

SOURCE: www.europeanpharmaceuticalreview.com/news/75890

Patient centricity: a winning formula

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Industry has taken a collective pause in an effort to re-evaluate and rethink longstanding approaches to drug development and commercialisation.

There has been considerable discussion about the concept of patient centricity in the pharmaceutical community, with attention being recalibrated on the ultimate goal — making it easier for the patient to reach improved health outcomes. This perspective is underpinned by the recognition that what is best for the patient will lead to beneficial outcomes for all stakeholders, including the drug company, the healthcare provider and the supporting community of associated service providers.

There is a famous quote from former United States Surgeon General, C. Everett Koop: “Drugs don’t work in people who don’t take them.” It is estimated that less than one third of all prescriptions written are actually filled at the pharmacy by patients. Wide-ranging studies have shown medication adherence rates for life-threatening diseases — including diabetes, heart disease and oncology — can be as low as 30–40%. With the benefit of interventional techniques and developing technologies, adherence rates have been shown to improve; however, these programmes are not broadly adopted within industry at scale and have neither significantly reduced the overall cost of healthcare nor benefitted large populations.

Patients may be non-adherent for a variety of reasons, some conscious and some unconscious. Certainly, we are all admittedly forgetful when it comes to taking our medicine on time or being diligent about timely refills of those prescriptions. Cost can also be a significant factor whereby patients will consciously stretch their medication supply or simply go off therapy. In either instance, doing so will hamper the health impact of their prescribed therapy or worse; taking a drug holiday while prescribed an anticoagulant could potentially put their life in jeopardy.

Other considerations may be unwanted side-effects or a lack of understanding about how to optimally take the medication, such as taking with food or alternatively avoiding food for some period of time, resulting in reduced effectiveness. Fear or general lack of understanding can also inhibit the path to improved health by affecting the patient’s perception of the medication and their willingness to be compliant.

Likewise, the patient may not physically experience the benefit of the drug and, in some instances, may have a negative perception owing to the unwanted side-effects. Hypertension is the classic example; the patient may have high blood pressure but generally not feel the effects of their disease. However, they may experience considerably unpleasant side-effects as a result of their course of treatment.

Likewise, a similar scenario plays out in popular cholesterol lowering medications. By scale, these two examples are noteworthy; in the US, with a population of more than 300 million people, of which 75% are adults, it is estimated that one in every three adults has hypertension, whereas 10–20% of adults have high cholesterol. A large-scale patient-centric approach to benefit medication adherence would have significant positive health and economic impacts.

Focusing patient centricity in clinical trials

In addition to challenges with patient adherence to medication in clinical trials, sponsors and study organisers are also constantly faced with hurdles such as patient recruitment and patient retention. As the industry is tasked with further expediting drug development and decreasing clinical study duration, FDA is increasingly requiring additional studies and further data to prove long-term safety and comparative effectiveness, including post-marketing studies once the drug is commercially available in the market.

This trend is coupled with an increasing percentage of drugs being brought to market for very specialised disease states and narrow therapeutic indications. This wave of specialised medicines and the ongoing need for treatment-naïve candidates, paired with cost pressures in the R&D sector, has increased the use of multinational studies. These complex studies in turn create the requirement for multilingual labelling. This can result in the creation of investigational medicinal product (IMP) study materials that may contain upwards of 16–20 languages on a single label.

Clinical trial professionals are left to balance all of these demands and creatively identify initiatives to keep the focus on the patient. At a surface level, these competing priorities may seem to be in direct conflict. However, when one looks at the situation from a broader perspective, the focus on patient centricity clearly generates tangible value and outweighs the short-term inefficiencies created by opting for a solution solely based on speed or cost.

Patient centricity in package design

A practical example of patient centricity in action can be found in package selection for investigational studies. When looking to initiate a clinical study, a sponsor company may be evaluating whether to choose a bottle or a unit dose blister in a calendarised format for their clinical study material.

Looking simply at the short-term criteria of expediting material for study initiation, when a difference of weeks or days can be considerable, the path of selecting a bottle would be a logical solution. It is a cost-effective packaging option, it is relatively “off the shelf” in its availability, it can be hand filled by a clinical packager with minimal start-up costs, has an acceptable stability profile for barrier properties and is child resistant.

Conversely, when evaluating the development of a unit dose adherence package, the company might find that it may involve a longer lead time for development and be more costly to produce. Looking from a short-term perspective and the immediate pressures of cost and expediting, the choice leaves little room for debate. However, if the sponsor company is taking a holistic approach with a focus on patient centricity, the broader economics absolutely point to the use of a patient-centric package.

Using a calendarised unit dose blister format or compliance/adherence packaging enables sponsor companies to both address the needs of the patient as well as positively impact the desire for better data, more efficient studies and lower total delivered cost. The use of this style of package allows patients to take medication exactly as prescribed and track their usage, rather than a bulk approach in a bottle format. Physicians can capture vital information on the package, including the specific date to start the therapy and any other pertinent notes for the patient. With the returned package, the patient can physically demonstrate to clinical providers that they have taken the product as prescribed. Furthermore, technologies are available that can provide real-time tracking of patient dosing, allowing for clinical interventions to ensure proper adherence while the study is in progress.

These technologies and principles extend to other delivery forms such as injectables. The ability to prompt, monitor and even track real-time information is a powerful tool. Likewise, with the advent of Bluetooth and nearfield communication technologies, packages with integrated technology can capture real-time information about side-effects or other vital information as patients take the medication during the course of treatment. Better adherence leads to healthier patients and more valuable study data.

Poor adherence can be rectified and corrected as it happens. Better information gathering can lead to improved patient retention, a significant cost in clinical trial administration and a persistent challenge in study duration. It is estimated that, in the industry, clinical studies on average have a 30% drop out rate. With more adherent investigational study patients, health outcomes are improved and better retention is realised, translating into reduced total delivered cost, more valuable data generated and studies executed more efficiently.

Patient centricity in clinical supply chain logistics

Another focus point for realising patient centricity in clinical trials is in the area of study design and administration. Considerable interest is being focused on Direct-to-Patient models, in which patients may minimise or in some instances avoid the need to come to a hospital or clinic to receive the study drug, as well as provide critical health feedback. In this scenario, patients are engaged by clinical trial or healthcare professionals in a home setting and the study drug is physically delivered to their home by a trained specialist. Clearly, this model is not applicable for all studies and disease states, but for certain programmes there can be considerable benefit to the patient and the study.

In certain geographies, patients in a traditional clinical study may have to travel significant distances to participate, which can considerably hamper patient recruitment and retention. In a Direct-to-Patient model, the study effectively comes to them. This model may increase the cost of study administration for the sponsor company; however, by executing the study in a more patient-focused approach, the sponsor company can realise significant benefit through patient recruitment and retention, again translating into better data, more efficient studies and a faster path to completion.

Patient centricity in a global world

One of the increasing challenges in taking a patient-centric approach to clinical study execution is the growth in multinational study execution. Often, supplies are designed to pool, so that multiple languages are provided and materials can be directed to individual countries as needed.

This scenario forces sponsor companies to either manage a multitude of language-specific supplies or focus on common supplies — whereby they condense information owing to the shear amount of text being added, often squeezed into a multi-page booklet.

Careful consideration must be paid to graphics that are common to all languages and cultures to ensure patients can clearly comprehend considerably distilled opening instructions, dosing regimens and other key information. Rather than a traditional pooled supply approach, some companies have developed newer strategies for just-in-time (JIT) labelling or late stage customisation logistics, whereby they label study materials according to country specific requirements at the time of drug dispatch.

This can reduce the complexity of a scenario in which they would be trying to accommodate 16 different languages on the same label in a multi-page booklet approach. This JIT strategy might decentralise supplies but may bring other benefits, such as meeting the language and cultural needs of patients in their geography, as well as those of the study administration.

Patient focus yields powerful results

The industry is only in the infancy of its journey towards patient centricity; but, it is clear that with a focus on the patient, many tangible benefits can be realised by drug companies in the development and commercialisation of life-saving medicines.

With so many significant breakthroughs during the past decade, it is exciting to see where this patient focused journey will lead as new patient breakthroughs are happening every day.

SOURCE: www.manufacturingchemist.com/news

ABPI expert urges to find new ‘blockbuster treatments’ for brain tumors

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

With the Government set to invest an additional £20 million into the research, diagnosis and development of treatments for brain tumours, we need to talk more about how we are going to find the next blockbuster treatments for these devastating diseases.

Nearly 11,500 people are diagnosed with a brain tumour every year in the UK with fewer than 15% surviving beyond 10 years. This week’s announcement from the from the Department of Health and Social Care – following the death of Dame Tessa Jowell – that they would be doubling investment for brain cancer research to £40 million is a welcome commitment to helping achieve a goal our industry shares: finding innovative new treatments and cures for these diseases.

The science is advancing in laboratories here in the UK and around the world, funded and supported by charities, universities and the pharmaceutical industry, collectively we are working to fight back against this terrible disease.

Among the 7,000 medicines currently being developed by the global pharmaceutical industry, there are 58 medicines in the pipeline for brain tumours, including gliomas. Companies are actively working to find better ways to speed up medicines development to get treatments to patients sooner.

In her speech to the House of Lords in January, Dame Tessa Jowell talked candidly about her glioblastoma diagnosis and called for greater collaboration in the fight against cancer. She also talked about the speeding up of drug trials by testing more than one at a time, saying: “I am not afraid, but I am fearful that this new and important approach may be put into the ‘too difficult’ box.”

The type of clinical trials Tessa Jowell talked about have many different names: adaptive randomisation, drop-the-loser, adaptive dose-finding, adaptive seamless and the list goes on.

The one thing they all have in common is flexibility. In trials like this – that we call adaptive design clinical trials – researchers can see how patients are responding to treatments and then change or stop parts of the trial in real time.

When used appropriately, trials like this may improve efficiency, reduce cost, maximize information gained and minimize risk to the patients and sponsors. Ultimately, drug development can be accelerated so that the right treatments can be delivered rapidly to the right patients. The UK is seen as a pioneer of innovative clinical trials and this involves collaboration between academia, the NHS, industry and medical research charities –  we must ensure we keep it that way in the future.

The issue is that these clinical trial types are not easy to design, plan or execute. An adaptive design will not rescue a poorly planned trial or ineffective treatment.

We need to make sure the regulatory authorities in the UK are not seen as a barrier to innovation; the MHRA and HRA are open to discussion and we need to encourage researchers and pharmaceutical companies to start conversations with them early in the process of planning an innovative clinical trial.

We think that adaptive design clinical trials could be the solution to speeding up the research and development of not only brain tumor treatments, but for all sorts of diseases. Research into small or rare patient populations could really benefit from these trials since they help us quickly rule out the drugs or drug combinations that aren’t working and give more patients the option to contribute to research and clinical trials.

We’re not alone. In February, the Department of Health and Social Care published their brain tumor research report which stated that, because brain tumors are one of the areas that have small patient populations, we need to think differently about how we conduct clinical trials and incorporate innovative trial designs.

The report provided practical recommendations for how we can work collaboratively to make quicker progress in this area. The next steps are to build on the UK’s existing strengths, ensure we have access to researchers with the right skills, and make sure that the right infrastructure is in place for us to make really make progress in this area.

Alongside their funding announcement, we welcome the Government’s commitment this week to accelerate the use of adaptive design trials. When used appropriately, drug development can be accelerated so that the right treatments can be delivered rapidly to the right patients – and that’s where the real benefit lies.

As we look to the future of cutting-edge research and development for blockbuster treatments, we know we need to make the case for innovative clinical trial design, talk more about the amazing science our researchers, companies and NHS are pioneering and encourage them to have open conversations with the UK regulators to ensure that innovative clinical research is safe and effective.

Together, we won’t rest until devastating brain tumours are a thing of the past.

SOURCE: www.news-medical.net/news

New indication for evolocumab in established atherosclerotic cardiovascular disease

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Amgen has announced announced that the European Commission (EC) has approved a new indication in the Repatha® (evolocumab) label for adults with established atherosclerotic cardiovascular disease (myocardial infarction, stroke or peripheral arterial disease) to reduce cardiovascular risk by lowering low-density lipoprotein cholesterol (LDL-C) levels.

With the expanded label now in place, Amgen is working with payers in Europe to remove prescribing barriers and expand access in order to reach patients with established cardiovascular disease who are at risk of another event.

“With its proven ability to prevent heart attacks and strokes, Repatha offers hope for one of the greatest health challenges we face today. However, the majority of patients in Europe who could benefit from treatment with a PCSK9 inhibitor remain unserved and at risk of a cardiovascular event,” said Anthony C. Hooper, executive vice president of Global Commercial Operations at Amgen. “To help ensure eligible patients around the world can access and benefit from Repatha, Amgen is willing to work in partnership with payers to help manage affordability concerns from increased patient access. Furthermore, we are committed to excellence in LDL-C management and collaborating with healthcare providers to deliver comprehensive solutions for patients.”

Of all the modifiable risk factors for heart attack and stroke, lowering high LDL-C is one of the most important and impactful.1,2 Yet, even among patients currently taking a lipid-lowering therapy, many patients still have high LDL-C levels and remain at risk for cardiovascular events. Repatha is a groundbreaking medicine proven to significantly lower “bad cholesterol” or LDL-C for high-risk patients who suffer from a combination of high LDL-C and cardiovascular disease, and who continue to struggle with lowering their LDL-C levels despite statin therapy.

“We know that patients with a previous history of cardiovascular events are at an increased risk of subsequent events, especially in the first year,”3-5 said Sean E. Harper, MD, executive vice president of Research and Development at Amgen. “With far too many patients at risk of recurrent cardiovascular events, we are pleased that the European Commission has approved Repatha to prevent heart attacks and strokes in adults with established atherosclerotic cardiovascular disease. The science clearly indicates that ‘lower LDL-C is better’ and this approval underscores the role for Repatha among high-risk patients for whom statins alone are not enough.”

The approval by the EC recognises the positive findings from the Repatha cardiovascular outcomes study (FOURIER), expanding the label to include data on the additional reduction and prevention of heart attacks, strokes and coronary revascularisations on top of maximally tolerated statin therapy. FOURIER showed reductions in the risk of heart attack by 27%, the risk of stroke by 21% and the risk of coronary revascularisation procedures by 22% in patients treated with Repatha and statin therapy compared to patients treated with placebo and statin therapy over a mean duration of 26 months.6

References

  1. National Heart, Lung, and Blood Institute. How To Prevent and Control Coronary Heart Disease Risk Factors. Accessed April 10, 2018
  2. Kuklina, EV. Centers for Disease Control and Prevention. Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol. United States, 1999–2002 and 2005–2008. MMWR. 2011;60(4):109–14
  3. Mohan KM, et al. Stroke. 2011;42:1489-94
  4. Bhatt DL, et al. JAMA.  2010;304:1350-7.
  5. Jernberg, T., et al. Eur Heart J. 2015. 36(19), 1163-117
  6. Sabatine MS, Giugliano RP, Keech AC, et al, for the FOURIER Steering Committee and Investigators. N Engl J Med. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. 2017;376:1713-22.

SOURCE: www.hospitalpharmacyeurope.com/editors-pick

Initiative launched to improve people’s understanding of eczema

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

A scheme to raise awareness about the emotional and physical impact of the most common type of eczema has been launched by a leading charity and a global biopharmaceutical company this month.

Scratch Beneath the Surfaceis a public health initiative established by Sanofi in collaboration with Allergy UK. The scheme aims to improve people’s understanding of atopic dermatitis, from what’s happening inside the body, to the emotional and psychological symptoms that can lie beneath the surface.

The condition affects over 1.5 million people in the UK,1,2 and in a survey, 80% reported that it impacted on their mood, mental health and well-being.

By improving awareness of atopic dermatitis, which is the most common type of eczema3 the initiative aims “to shift any misconceptions among the general public and combat the stigma related to the disease, which will in turn, lead to those affected feeling a greater sense of support and understanding”, Sanofi said.

Commenting on the launch of the initiative, Carla Jones, Allergy UK’s chief executive said: “Atopic dermatitis is often dismissed as a simple skin condition or rash that can be soothed with moisturisers, but people don’t realise that it’s a long-term and potentially life-altering disease.”

“There is a huge sense of frustration amongst those affected, who feel that eczema and atopic dermatitis are often misunderstood. Even simple day-to-day tasks like walking up the stairs, bathing and getting dressed can be painful for someone experiencing a flare-up,” she said.

A UK-wide survey of people with moderate-to-severe atopic dermatitis4found that the disease can impact every aspect of an individual’s life. Difficulty sleeping emerged as a significant problem, affecting 75% of those surveyed; with the constant itching and pain when trying to sleep, leaving people feeling tired and restless in the day.4

For some people, the impact of unpredictable flare-ups and feelings of self-consciousness can also lead to symptoms of anxiety or depression.4

Some 80% of survey participants reported that atopic dermatitis has a direct impact on their mood. In interviews, participants reported feeling anxious, especially in public and social settings, and feeling that they’re being looked at and judged by others.4

57% admitted they feel depressed because of their skin with some taking antidepressants to try and help the situation.4 And 60% of male participants and 55% of female participants noted that their self-esteem and self-confidence is frequently impacted due to their skin condition.

Commenting on the findings, Dr Anthony Bewley, consultant dermatologist at Whipps Cross University Hospital, and the Royal London Hospital, said: “Despite affecting over one and a half million adults in the UK, too few people understand the inflammatory and unpredictable nature of atopic dermatitis.

“For many people, it’s the unseen consequences, the emotional and psychological impact hiding beneath the surface that makes the disease most difficult to live with. Itchy skin is considered to be one of the worst symptoms; it can be physically debilitating.

“However, the associated restlessness, sleepless nights, and sore, broken skin can have a severe impact on a person’s daily functioning, mental health and self-esteem,”  he said.

References

  1. Nutten S. Atopic Dermatitis: Global Epidemiology and Risk Factors. Ann Nutr Metab 2015;66 (suppl 1): 8-16.
  2. Office for National Statistics. 2014 UK mid-year population estimate. Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/populationandmigration/populationprojections/bulletins/nationalpopulationprojections/2015-10-29 (Accessed April 2018).
  3. NHS Choices. Atopic Eczema (Atopic Dermatitis). Available at: https://www.nhs.uk/conditions/atopic-eczema/  (Accessed April 2018).
  4. Sanofi data on file, March 2018.

SOURCE: www.hospitalpharmacyeurope.com/editors-pick

SMC approves licence for liver cancer treatment

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Stivarga® (regorafenib) has been accepted by the Scottish Medicines Consortium (SMC) as a monotherapy for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with Nexavar® (sorafenib).1

Regorafenib is the first medicine to be specifically licensed for second-line use in patients with HCC who had formerly been treated with sorafenib, the German multinational pharmaceutical company Bayer has announced.

The medicine is taken orally and works by slowing down the growth and spread of cancer cells by cutting off the blood supply that keeps cancer cells growing.2

Judi Rhys, chief executive of the British Liver Trustsaid: “A diagnosis of hepatocellular carcinoma (HCC) is truly devastating – it is a horrendous type of liver cancer that is often diagnosed very late with few treatment options.

“We are delighted that the Scottish Medicines Consortium (SMC) has accepted the Trust’s evidence on behalf of patients and agreed to the use of this drug for patients in Scotland.

Evidence shows that outcomes for people with advanced liver cancer are particularly poor, so this is an important step.”

She added the decision “highlights a two tier system where patients in other parts of the UK are denied access to this new treatment that can improve outcomes”.

The positive SMC announcement follows the recent decision from the National Institute for Health and Care Excellence (NICE) to not recommend the use of regorafenib on the NHS in England.3

Amanda Cunnington, head of patient access, Bayer UK said regorafenib was “the first advancement in licensed treatment for liver cancer patients in nearly a decade”and that it offers “the first and only approved second-line systemic treatment option which could significantly improve patients’ overall survival”.

Regorafenib is licensed based on data from the international, multicentre, placebo controlled Phase III RESORCE [Regorafenib after Sorafenib in patients with hepatocellular carcinoma; NCT 01774344] trial. The trial investigated patients with HCC whose disease had progressed during treatment with sorafenib.4

In the trial, regorafenib plus best supportive care (BSC) was shown to provide a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo plus BSC (10.6 vs. 7.8 months, respectively, (HR 0.62; 95% CI 0.50-0.79; p=0.000017)) which translates to a 37% reduction in the risk of death over the trial period.4

Adverse events observed in the RESORCE trial were generally consistent with the known safety profile of regorafenib.4 The most common (>=30%) treatment-emergent adverse events were hand–foot skin reaction, diarrhoea, fatigue and hypertension.4

HCC is the most common type of primary liver cancer.5 Liver cancer is a difficult-to-treat cancer with an annual mortality rate of 48,000 in the EU.6 Globally, it is the second leading cause of cancer-related deaths.6In the UK, there are over 5500 new cases of primary liver cancer diagnosed each year, which is around 15 patients each day.7

References

  1. SMC. regorafenib 40mg film-coated tablets (Stivarga®). SMC No 1316/18. Bayer plc. April 2018. Available at: http://www.scottishmedicines.org.uk/files/advice/regorafenib__Stivarga__FINAL_March_2015Revised_250315_for_website.pdf (Last accessed May 2018).
  2. European Medicines Consortium (EMC) Stivarga® Patient Leaflet. Available at: https://www.medicines.org.uk/emc/files/pil.1263.pdf (Last accessed April 2018).
  3. National Institute for Health and Care Excellence (NICE) Regorafenib for previously treated advanced hepatocellular carcinoma. Technology appraisal guidance [TA514] Published date: 21 March 2018.  Available at: https://www.nice.org.uk/guidance/ta514/chapter/1-Recommendations  (Last accessed April 2018).
  4. Stivarga® (regorafenib) Summary of product characteristics. Bayer HealthCare. September 2017. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Info… (Last accessed April 2018).
  5. Cancer Research UK. Liver Cancer Types. Available at: http://www.cancerresearchuk.org/aboutcancer/liver-cancer/types. (Last accessed April 2018).
  6. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012.http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx (Last accessed April 2018).
  7. Cancer Research UK. Liver Cancer Incidence Statistics. Available at http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/livercancer/incidence#heading-Zero  (Last accessed April 2018).

SOURCE: www.hospitalpharmacyeurope.com/editors-pick

Scientists discover mutation that causes PARP inhibitor resistance

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Scientists have made a major discovery having identified a mutation that gives cancer cells resistance to AstraZeneca’s Lynparza and other PARP inhibitors.

The findings could help predict which patients are likely to develop resistance to treatment with PARP inhibitors and thus allow doctors to tailor treatment at the earliest opportunity.

Using a gene editing technique a team at the Institute of Cancer Research, London, were able to identify a specific mutation in the PARP1 protein that stops PARP inhibitors from working.

The authors note that testing for this mutation could deepen personalisation to an already targeted treatment, not only helping to shape decisions on whether to initiate treatment with PARP inhibitors but also when to switch patients to alternative options.

“The evolution of cancers into drug resistant forms is a major challenge we face in getting cancer treatments to work,” noted study leader Professor Chris Lord, Professor of Cancer Genomics at The ICR.

“We hope our research will help doctors use the best drug right from the outset, respond quickly to early signs of resistance, and work out the best ways to combine treatments to overcome drug resistance.”

“This important finding could in future allow clinicians to determine who would benefit most from these drugs, or to track when they are becoming less effective and when a change of treatment might be appropriate,” said Baroness Delyth Morgan, chief executive at Breast Cancer Now.

“Studies like this, which build on the development of PARP inhibitors as a brand new treatment option for some women with breast cancer, could help take us a step closer to an even more personalised approach to treating the disease.”

The research was funded by Cancer Research UK and Breast Cancer Now, and published in the journal Nature Communications.

SOURCE: www.pharmatimes.com/news