Category Archives: Analgesics

Amgen CEO says Aimovig is “one of most successful launches”

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

As biosimilars start to eat into sales of its blockbuster biologic drugs, Amgen needs new products to deliver growth – and it says migraine therapy Aimovig is off to a great start.

Chief executive Bob Bradway told investors on the company’s third-quarter results call that Aimovig (erenumab) is “shaping up to be one of the industry’s most successful recent launches” with sales reaching $22m in the quarter, ahead of analyst expectations.

“People suffering from migraine and their physicians have been waiting for years for an effective new therapy and they’ve reacted very well to Aimovig,” he said. The company estimates that more than 100,000 patients have taken the Novartis-partnered CGRP inhibitor since its launch in May as a once-monthly, self-injected preventive treatment for migraines.

The strong take-up has come despite approvals for rival CGRP inhibitors from Teva and Lilly, and Amgen says its first-mover advantage is backed up by a patient-friendly delivery device, as well as a willingness by healthcare payers to cover the product thanks to a price that encourages access.

The company is also making much of the fact that Aimovig is the only drug that targets the CGRP receptor rather than the CGRP protein itself, although for now there’s no strong evidence to suggest that confers a clinical advantage.

There’s no doubt that the rapid roll-out comes from pent-up demand for the drug among people with migraine who still suffer headaches despite other therapies. However Amgen’s commercial head Murdo Gordon said he believes “we’re scratching the surface of helping chronic migraine sufferers [and] we think that we’ll see continued demand growth.”

Overall, Amgen posted a 2% rise in revenues to $5.78bn in the quarter, despite pressure on older drugs like while blood cell booster Neulasta (pegfilgrastim) which showed the first signs of weakness from biosimilar competition after Mylan/Biocon launched their Fulphila rival in July. TNF inhibitor Enbrel (etanercept) also fell 5% in the face of competition from newer drugs in indications such as psoriasis.

There was also disappointing news once again for cholesterol drug Repatha (evolocumab) which rose 35% to $120m but missed expectations. Last week, Amgen reduced its price by 60% to $5,850 in a bid to kickstart sales growth and overcome payer resistance to the drug.

“This should substantially lower their out-of-pocket costs and lower the abandonment rate which is as high as 75%,” said Gordon, who said the cut was necessary to compete and would build much-needed volumes at the expense of near-term sales.

The Repatha discount comes as the US administration is ramping up the pressure on the biopharma industry on drug pricing, most recently proposing a reference pricing model to bring process closer into line with other affluent nations.

Commenting on the overall environment and how it looks likely to develop in 2019, Bradway said that the US has benefitted enormously from a market which allows patients to access new therapies “more quickly and more comprehensively than in other countries.”

“We think what’s required is more innovation, not less, and the system that enables people to get access to that innovation swiftly,” he suggested.

SOURCE: www.pmlive.com/pharma_news

Teva wins FDA OK for crucial migraine drug

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Vital to Teva’s turnaround, Ajovy will challenge Novartis/Amgen’s Aimovig.

Teva has secured US approval for migraine drug Ajovy, a key part of new chief execeutive Kåre Schultz’s turnaround plan for the company.

The FDA approved the CGRP inhibitor for the prevention of migraine in adults with either monthly or quarterly dosing, based on two phase 3 studies showing that it could reduce the number of migraine days over a 12 -week period compared to placebo.

Ajovy (fremanezumab) is the second CGRP inhibitor to be approved for marketing after Novartis and Amgen’s Aimovig (erenumab), which got the green light in May and is dosed monthly, and ahead of late-stage rivals from Eli Lilly (galcanezumab) and Alder Biopharma (eptinezumab).

Teva would have been earlier to market but the FDA review for its products was delayed by three months while it sorted out some manufacturing issues. With Lilly due to hear from the FDA any day now, potentially setting up a three-way marketing battle, the Israeli drugmaker will be hoping the three-monthly dosing option will be popular with doctors and patients – particularly as there seems to be little to separate the antibodies when it comes to efficacy.

In a statement, Teva said that it had set a list price of $575 for the monthly dose and $1,725 for the quarterly dose, giving an annual cost of $6,900 before rebates and discounts – exactly the same level as Novartis and Amgen positioned Aimovig, and in line with stablished therapies like Allergan’s Botox.

It is estimated that with discounts the annual cost of the drugs could be around the $5,000 mark. However, the US-based Institute for Clinical and Economic Review (ICER) said recently that – even at that lower price – the new drugs should only be used with prior authorisation and after other preventive options such as Botox and anti-epilepsy drugs like topiramate because their long-tern safety is still unclear.

It is estimated that more than 36 million people in the US suffer from migraines, with around 40% of these would be suitable for preventive treatment, and that has led some analysts to predict buoyant sales of the CGRP inhibitors.

GlobalData said recently that it expects the market for migraine drugs to grow at more than 10% a year to reach almost $9bn by 2026, with the prevention category driven by the injectable CGRP inhibitors.

”Market share is going to come down to…variables such as frequency of administration, position to market, and market access strategy,” according to GlobalData analyst Rahael Maladwala.

“Each drug has its own set of advantages; Aimovig will be the first to market, Eli Lilly’s has significant experience in marketing drugs, and an extensive sales force, while both of the other drugs have a quarterly dosing regimen compared to monthly.”

On balance, GlobalData is putting Aimovig out in front in 2026 given its first-mover advantage generating nearly $1.4bn in sales in the seven major pharma markets (US, France, Germany, Italy, Spain, UK, and Japan).  Teva filed Ajovy in Europe earlier this year, but here it will also lag behind Aimovig as Novartis and Amgen picked up EMA approval for their drug in July.

Analysts at Jefferies have suggested Ajovy could become a $500m product in 2022, which will go some way towards counteracting the decline in sales of Teva’s blockbuster multiple sclerosis therapy Copaxone (glatiramer acetate), its rapidly ageing cash-cow product.

Since Schultz took the helm last year, Teva has been shedding staff and restructuring the business to cut costs, selling off its women’s health business for almost $2.5bn in order to pay down a very high level of debt stemming from its $39bn acquisition of Allergan’s generics business Actavis in 2015.

Ajovy is one of 23 New Drug Application (NDA) approvals Teva is targeting between fiscal 2019 and fiscal 2023 to help replace Copaxone and drive top-line growth, along with other new products such as movement disorder therapy Austedo (deutetrabenazine).

SOURCE: www.pmlive.com/pharma_news

Paracetamol use in infancy may increase the risk of asthma

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

A study has found that paracetamol use in infancy, as well as genetic factors, may increase the likelihood of developing asthma.

A study by researchers from the University of Melbourne, Australia identified how infants who take paracetamol during the first two years of life could be at a higher risk of developing asthma in their late teens.

Xin Dai, a PhD candidate at the University, and her colleagues explained how the link between paracetamol use and asthma seemed to be the strongest in individuals with a particular variant of the glutathione S-transferase (GST) gene, GSTP1.

GSTP1 is part of a gene family which encodes gene crucial for some life processes, detoxification and toxification mechanisms. The genes are upregulated in response to oxidative stress, and are overexpressed in tumours.

GST genes contain the information needed to make the antioxidant glutathione, which clears the effect of exposure to toxins in the body and the lungs.These actions help to prevent damage to cells and inflammation.

“Paracetamol, on the other hand, consumes glutathione, reducing the body’s capacity to deal with toxic exposure,” said Ms Dai. “We hypothesised that people who did not have full GST enzyme activity because of common genetic variations or deletions may be more susceptible to adverse effects on the lungs from paracetamol use.”

The researchers investigated 620 children who had been followed form birth to the age of 18, as part of the Melbourne Atopy Cohort Study. These children were selected before birth, as it was deemed that they had a high risk of developing an allergy-related disease. At least one family member (father, mother or sibling) had a self-reported allergic disease, such as asthma, eczema, hay fever or a severe food allergy.

After the birth of each child, a nurse rang the family every four weeks for the first 15 months, and then at 18 months and at two years old to ascertain the number of time the infant was given paracetamol. As the child reached the age of 18, a blood or saliva sample was given and tests were conducted to identify variants of GST genes.

The participants were also assessed for asthma, and a spirometry test measured the amount of air inhaled and exhaled when breathing through a mouthpiece.

“We found that children with the GSTP1 Ile/Ile variant had 1.8 times higher risk of developing asthma by the age of 18 years for each doubling of the days of paracetamol exposure when compared to children who were less exposed,” said Ms Dai. “In contrast, increasing paracetamol exposure in children who had other types of GSTP1 did not alter the risk of asthma.

In addition, we found some weak evidence that paracetamol use in the first two years of life may be associated with reduced lung function in adolescence regardless of which variants of the GST genes the children had.”

The researchers stressed that the study showed an association between paracetamol and asthma, and not that one caused the other. To establish this, further research would be necessary.

She concluded: “Our findings provide more evidence that paracetamol use in infancy may have an adverse effect on respiratory health for children with particular genetic profiles and could be a possible cause of asthma. However, these findings would need to be confirmed by other studies and the degree of adverse effect better understood before this evidence could be used to influence practice and before guidelines on paracetamol use are altered.

“There is mounting evidence that the GST superfamily of genes, including three major classes -GSTM1, GSTT1 and GSTP1 – are associated with various diseases, including cancers, asthma, atherosclerosis, allergies, Alzheimer’s and Parkinson’s disease. Our study adds to this body of evidence.”

The study was presented at the European Respiratory Society International Congress.

SOURCE: www.europeanpharmaceuticalreview.com/news/79189

Can sugar pills actually relieve chronic pain?

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

A sugar pill could benefit patients suffering from chronic pain with specific brain anatomy and psychological traits.

Doctors could begin to prescribe sugar pills for some patients suffering from chronic pain, based on their brain anatomy and psychology. The pills are said to reduce their pain as effectively as new powerful pain relief drugs.

Scientists from Northwestern University have shown that they are able to reliably identify patients with chronic pain, that will respond to a sugar placebo pill based on their brain anatomy and psychological characteristics.

The scientists also suggests that it’s not necessary to hide this from the patient.

“Their brain is already tuned to respond,” said senior study author Professor of Physiology at  Northwestern University Feinberg School of Medicine, Dr Vania Apkarian.

“They have the appropriate psychology and biology that puts them in a cognitive state that as soon as you say, ‘this may make your pain better,’ their pain gets better.”

“You can tell them, ‘I’m giving you a drug that has no physiological effect but your brain will respond to it,’” he said. “You don’t need to hide it. There is a biology behind the placebo response.”

For the study, 60 patients with chronic back pain were randomised into two groups. The first group did not know whether they received the drug or the placebo, and the second group included people who came to the clinic, but received neither the drug nor the placebo.

The scientists did not study the people receiving the real drug, instead focusing on those receiving the sugar pill. The second group was used a control.

Individuals who had a decrease in their level of pain had similar brain anatomy. The right side of their emotional brain was larger than the left, and they had a larger cortical sensory area than people who were not responsive to the placebo. Psychologically, these individuals were also emotionally self-aware, sensitive to painful situations and mindful of their environment.

The researchers mention three main potential benefits: prescribing non-active drugs rather than active drugs, eliminating the placebo effect from drug trials, and reducing healthcare costs.

“It’s much better to give someone a non-active drug rather than an active drug and get the same result,” Prof Apkarian said. “Most pharmacological treatments have long-term adverse effects or addictive properties. Placebo becomes as good an option for treatment as any drug we have on the market.”

“Clinicians who are treating chronic pain patients should seriously consider that some will get as good a response to a sugar pill as any other drug,” he concluded. “They should use it and see the outcome. This opens up a whole new field.”

The study was published in Nature Communications.

SOURCE: www.europeanpharmaceuticalreview.com/news/79045

FDA greenlights first non-opioid therapy to manage symptoms of opioid withdrawal

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

As the opioid epidemic continues to grip the US as the leading cause of deaths in those under the age of 50, the FDA has made an important leap with the approval of Lucemyra (lofexidine hydrochloride) for managing the symptoms of opioid withdrawal in adult patients – the first non-opioid therapy for this purpose.

While this is an important step forward, the therapy is not a cure-all solution and is not guaranteed to prevent withdrawal symptoms and may only lessen their severity, and is only approved for use for up to 14 days. These symptoms can include anxiety, muscle aches, agitation, sweating, nausea, vomiting, problems sleeping and drug cravings, which can occur both in patients with opioid use disorder and in those using the drugs as directed by a medical professionals.

An oral, selective alpha 2-adrenergic receptor agonist, Lucemyra works by reducing the release of norepinephrine, which is thought to be a key element in the symptoms of opioid withdrawal. The regulator’s decision was based on two trials of 866 patients who met the Diagnostic and Statistical Manual-IV criteria for opioid dependence who were physically dependent on opioids and undergoing abrupt opioid discontinuation. In these trials, it was found that patients taking Lucemyra reported lower severity of withdrawal symptoms according to the Short Opiate Withdrawal Scale of Gossop.

The fast-tracked decision comes off the back of a positive opinion in March from an independent FDA advisory committee. The regulator also specified that it requires 15 postmarketing studies to be conducted to support the drug’s longer-term use.

“As part of our commitment to support patients struggling with addiction, we’re dedicated to encouraging innovative approaches to help mitigate the physiological challenges presented when patients discontinue opioids,” said FDA Commissioner Scott Gottlieb. “We’re developing new guidance to help accelerate the development of better treatments, including those that help manage opioid withdrawal symptoms. We know that the physical symptoms of opioid withdrawal can be one of the biggest barriers for patients seeking help and ultimately overcoming addiction. The fear of experiencing withdrawal symptoms often prevents those suffering from opioid addiction from seeking help. And those who seek assistance may relapse due to continued withdrawal symptoms. The FDA will continue to encourage the innovation and development of therapies to help those suffering from opioid addiction transition to lives of sobriety, as well as address the unfortunate stigma that’s sometimes associated with the use of medication-assisted treatments.”

SOURCE: www.pharmafile.com/news/517386

Three medicines step closer to EU approval

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Three medicines treating HIV, pain and cancer have been recommended for approval by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) at its latest meeting.

Gilead’s Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) was endorsed as a treatment HIV-1 infection.

The once-daily single tablet regimen has shown high rates of virologic suppression and no treatment-emergent resistance through 48 weeks in Phase III clinical trials involving treatment-naïve adult patients and among virologically suppressed adults who switched regimens.

The marketing application contains data from four Phase III studies in which the regimen met its primary goal of non-inferiority to ViiV Healthcare’s flagship drug dolutegravir (DTG) at 48 weeks.

The therapy was approved in the US in February.

The CHMP also recommended approval of one hybrid medicine, FGK Representative Service GmbH’s Dzuveo (sufentanil), for the treatment of pain.

Hybrid applications rely in part on the results of preclinical tests and clinical trials for a reference product and in part on new data.

The opioid produces analgesia by activating μ-opioid receptors primarily within the central nervous system, and its most common side effects are nausea, vomiting and pyrexia.

Elsewhere, the Committee voiced its support for Obvius Investment BV’s generic medicine Carmustine Obvius (carmustine), for the treatment brain tumours, non-Hodgkin’s lymphoma and Hodgkin’s disease.

SOURCE: www.pharmatimes.com/news

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

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

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

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

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

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

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

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

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

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

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

SOURCE: www.europeanpharmaceuticalreview.com/news/73703

Migraine maven Lilly finds ‘understanding gap’ between patients, nonpatients in new survey

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Disconnects still exist in perceptions around migraines.

Surveying both migraine sufferers and average consumers, Eli Lilly found significant understanding gaps between the two.

For instance, migraine patients estimated their pain episodes lasted an average of 31 hours, while nonsufferers guessed the average fell around 21 hours. Migraine patients also rated the pain they felt much higher than the average person’s rating of what they imagined the pain to be.

“There is a huge stigma in migraine,” said Sheena Aurora, a physician who has treated migraine patients and is now a medical fellow at Eli Lilly. “… Sometimes even people with migraines don’t realize the impact of their disease. When I treated patients with migraines, I would ask them how many migraine headache days did they have, and they would have to stop and think about it.”

Lilly undertook the survey to determine migraine perceptions among three groups of people: migraine sufferers, caregivers and loved ones, and consumers who didn’t know anyone who suffers from migraines.

Other poll findings included that migraine patients feel stressed and that they’re missing out on life. Patients reported that migraines had prevented them from doing what they wanted in their lives for an average 7 days out of the previous 30 days.

During the previous year, the migraines had been severe enough to force them to miss an average of 7.4 important events, such as birthday or holiday gatherings. And an overwhelming majority—82%—agreed that it is stressful to have an unpredictable disease like migraine.

“By highlighting their unmet needs and continuing to do that, then we can help patients talk to their physicians, help physicians recognize their impact and perhaps even help payers understand the impact of migraines,” Aurora said.

She noted that the survey and other studies around migraines are important as new treatments created specifically for migraines come to market. Of the four currently FDA-approved drugs, none were designed exclusively for migraines, a fact that is often seen in low adherence when patients can’t take the side effects or don’t get enough relief, Aurora said.

Lilly is currently working to bring a new class of migraine therapy to market. The Indianapolis drugmaker has already filed a Biologics License Application with the FDA for its CGRP inhibitor maintenance drug galcanezumab, which is eventually expected to go up against contenders from companies including Amgen and Teva.

Meanwhile, Lilly’s first-in-class acute migraine candidate lasmiditan is in late-stage trials with expectations for FDA filings this year.

SOURCE: www.fiercepharma.com/marketing

FDA raises death count from kratom, a natural opioid

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Facing a rising death toll associated with the use of kratom, the U.S. Food and Drug Administration said it’s overseeing the recall and destruction of a “large volume” of potentially deadly dietary supplements containing this herb, which some people believe alleviates symptoms that come with opioid withdrawal.

The action involves supplements made by Divinity Products Distribution of Grain Valley, Missouri, and distributed under brand names including Enhance Your Life and Divinity, the Food and Drug Administration said in a statement Wednesday. In cooperation with the FDA, the company agreed to stop selling products containing kratom.

“Scientific data we’ve evaluated about kratom provides conclusive evidence that compounds contained in kratom are opioids and are expected to have similar addictive effects as well as risks of abuse, overdose, and in some cases, death,” FDA Commissioner Scott Gottlieb said in the release.

“The agency has also been assessing peer-reviewed research and a growing number of adverse event reports associated with kratom use, including 44 reported deaths,” the FDA said.

The agency has for years had doubts about kratom, a plant grown in Asia. It imposed import alerts on the substance in 2012 and 2014, and in November it said it knew of 36 fatalities associated with kratom, which has no FDA-approved therapeutic uses.

“Our death count has grown from 36 to 44,” FDA spokesperson Lyndsay Meyer told CBS MoneyWatch, adding that the deaths occurred from April 2011 through December 2017. “A recent death report to us, where the person died of opioid use, the only drug in that person’s system was kratom.”

With the U.S. in the midst of an opioid epidemic, the agency is concerned that people are viewing kratom as a natural alternative to prescription drugs, when there’s little to no difference between them, Meyer said.

“People are using kratom to get off opioids, when in fact it is opioids,” she said. “Heroin comes from a plant. Just because it comes from a plant doesn’t mean it’s safe,” she added.

Additionally, the FDA said it’s probing an outbreak of salmonella infections tied to products containing kratom. The Centers for Disease Control and Prevention (CDC) on Tuesday said 28 people in 20 states have been infected and 11 hospitalized after consuming kratom in pills, powder or tea.

The CDC and FDA advised against consuming kratom — also known as thang, kakuam, thom, ketom and biak — in any form.

In November, the FDA reported that calls to U.S. poison control centers regarding kratom rose 10 times from 2010 to 2015, with hundreds of calls coming in each year.

SOURCE: www.cbsnews.com/news

Ibuprofen better choice over oral morphine for pain relief in children

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Widely available ibuprofen is a better choice for pain relief in children who have undergone minor surgery, as it has fewer adverse effects compared with oral morphine.

Widely available ibuprofen is a better choice for pain relief in children who have undergone minor orthopaedic outpatient surgery, as it has fewer adverse effects compared with oral morphine, according to results from a clinical trial published in the Canadian Medical Association Journal.

“This result suggests that adequate pain management should be an important goal of care, even after minor outpatient surgery, and that more effective pharmacologic and nonpharmacologic strategies should be explored,” writes Dr Naveen Poonai, Clinician Scientist, Lawson Health Research Institute, and Associate Professor, Emergency Medicine, Department of Paediatrics, Schulich School of Medicine & Dentistry, Western University, with co-authors.

The study included 154 children aged 5 to 17 years who underwent minor orthopaedic surgery, such as keyhole surgery on joints, ligament and tendon repair, suture or hardware removal at London Health Sciences Centre in London, Ontario.

In the first 24 hours, more than 80% of the children in the study needed pain relief at home. Pain scores for children in both the oral morphine and ibuprofen groups were similar, but the children receiving oral morphine reported more adverse effects, such as nausea, vomiting, drowsiness, dizziness and constipation.

“Morphine did not provide superior analgesia but was associated with significantly more adverse effects, making ibuprofen a better analgesic option,” write the authors.

They note that as neither treatment completely relieved pain, more research is needed into effective pain relief, especially for more severe pain.

Oral morphine use at home has not been previously studied in children who have had minor surgery nor has it been compared with ibuprofen.

SOURCE: www.europeanpharmaceuticalreview.com/news/67835