FDA raises death count from kratom, a natural opioid

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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

Tandem’s insulin pump can predict and prevent hypo’s

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New predictive software integrated into an insulin pump can reduce time spent in hypoglycaemia compared with sensor-augmented pumps in type 1 disease.

Medical device firm Tandem Diabetes Care has produced results from its PROLOGtrial, which it will submit to the FDA, potentially paving the way for the product’s launch this summer.

Manufacturers of insulin pumps are competing to produce ‘intelligent’ pumps that can monitor and automatically respond to levels of insulin in patients’ blood streams.

Tandem is competing with rivals such as Medtronic, which has produced a hybrid closed-loop system that adjusts basal insulin delivery based on blood glucose measurements, although users still input mealtime doses and calibrate the system.

Tandem is hoping that the experimental predictive low glucose suspend (PLGS) feature on its t:slim X2 insulin pump will give it the edge.

The company has been updating features on its pump over the years, allowing patients to improve and tweak their device using software updates.

The PLGS  system works by suspending insulin delivery when low blood glucose is predicted, and automatically resuming it when glucose levels begin to rise.

Trial data announced at the Annual Conference on Advanced Technologies and Treatment for Diabetes (ATTD) in Vienna showed the system achieved the primary outcome of reducing time sent in hypoglycaemia compared to sensor-augmented pump therapy alone.

Use of the system during a 3-week period at home reduced the number of sensor glucose readings below 70 mg/dL by 31% compared to the control period using a standard CGM-integrated t:slim X2 Pump without automated insulin suspension.

This marked reduction of time spent in low glucose was accomplished without any increase in the rate of hyperglycemia.

The PROLOG study was a multi-centre, randomised crossover clinical trial comparing two three-week periods of at-home insulin pump use, one period using the t:slim X2 Pump with PLGS, and another period using a standard CGM-integrated t:slim X2 Pump without automated insulin suspension.

The study included 103 participants with type 1 diabetes age 6 to 72 at four research centres across the United States and was co-ordinated by the Jaeb Center for Health Research in Tampa, Florida.

The mean A1C of participants entering the study was 7.3%, with the majority already using a pump (83%) and/or CGM (84%). The primary endpoint of the study was to demonstrate a reduction in the percentage of CGM values below 70 mg/dL when using Tandem’s PLGS feature.

Hypoglycaemia is a huge problem for people being treated for their diabetes and has been linked to increased risk of cardiovascular problems.

The problem is made worse because patients in this state do not realise that they are having a hypoglycaemic episode as their judgement becomes impaired.

Kim Blickenstaff, president and CEO of Tandem Diabetes Care, said: “Reducing the risk of hypoglycemia has been the most requested feature of automated insulin delivery in our market research, due to the severity of the complications when left untreated. The data from this study supports our mission to improve the lives of people with diabetes through new innovations, such as the t:slim X2 Pump with Basal-IQ technology.”

SOURCE: www.pharmaphorum.com/news

Nusinersen improves motor function of children with SMA

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Clinical trial shows treatment is effective for children with spinal muscular atrophy.

Children with later-onset spinal muscular atrophy (SMA) were more likely to show gains in motor function when treated with a new medication compared to children receiving a sham procedure, according to a new study. The study demonstrates the impact the drug, nusinersen, can have on older patients with this progressive neuromuscular disorder.“This treatment is transformative for the entire SMA community,” said Dr Richard S. Finkel, the Chief of Neurology at Nemours Children’s Hospital in Orlando and the senior author of the study. “One thing we have learned, though, is that the closer to symptom onset that children begin treatment, the more substantial the improvement in motor function. However, even with delayed use, we observed significant improvements in older children with SMA on nusinersen.”

SMA is classified based on the age at symptom onset, as well as the most advanced motor milestone attained during development. Past studies have evaluated the safety of nusinersen in SMA Type 1, the most severe form that affects infants, usually before six months of age and who do not achieve sitting. Children with SMA Type 2 experience symptoms after six months of age and attain sitting before experiencing the muscle weakness and decline in motor function that are hallmarks of this genetic disease.

Before nusinersen, no targeted drug treatments were available for SMA. This treatment modifies the SMN2 gene with an antisense oligonucleotide (ASO), a tiny fragment of synthetic DNA, injected directly into the spinal fluid. The DNA gets absorbed into nerve cells of the spinal cord to increase production of a protein required for neuromotor development.

The researchers noted greater improvements in a motor function score in children treated with nusinersen for at least six months. In total, 57 percent of children in the nusinersen group had an increase of at least three points in functioning scores from the start of the trial to the end of the examination period, compared with 26 percent of patients in the control group that achieved the same level improvement.

The study, known as the CHERISH trial, enrolled 126 children ages 2 to 12 with SMA Type 2 in a multicenter, randomised, double-blind, sham-controlled study from November 2014 through February 2017 to determine the safety and efficacy of the drug in these older patients. Children were administered four doses over nine months, followed by a six-month examination period, before being invited to participated in an open-label extension study.

There are some limitations to the study, including the strict eligibility criteria, which enrolled a more homogeneous and younger group of patients than those in clinical practice. Participants were required to be able to sit independently at the start of the study, with no severe contractures or scoliosis, limited ventilation support, and no use of a gastric feeding tube.

The availability of an effective treatment has led Dr Finkel and colleagues to spearhead efforts to have SMA included in the Health Resources and Services Administration’s Recommended Uniform Screening Panel, a newborn screening panel of conditions that warrant immediate identification after birth. The panel has recently approved this recommendation and is awaiting signature by the head of Health and Human Services. If included, infants with SMA could be diagnosed routinely and treated before symptoms appear.

The study has been published in the New England Journal of Medicine.

SOURCE: www.europeanpharmaceuticalreview.com/news/72844

Type 1 diabetes trial reaches full enrollment

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A clinical trial studying type 1 diabetes has reached full enrollment.

Interim data analysis from T-Rex study expected in the first quarter.

The Sanford Project: T-Rex Study, a Phase 2 clinical trial conducted collaboratively by Sanford Health and Caladrius Biosciences, Inc., (Caladrius)(Nasdaq: CLBS), has completed enrollment of 110 children with type 1 diabetes. The study started with two sites at Sanford Health in Sioux Falls, South Dakota, and Fargo, North Dakota, and expanded to 13 additional sites across the United States.

The project is studying the potential of CLBS03, Caladrius’ cell therapy consisting of each patient’s own regulatory T cells, or Tregs, to help the body fight type 1 diabetes.

Subjects will be followed for two years, with the primary endpoint of persistence of insulin production at one year after treatment. A planned, interim analysis of the first half of the participants at six months after treatment is expected by the end of the first quarter.

“I am thrilled to have reached this important milestone,” said Kurt Griffin, M.D., Ph.D., director of clinical trials for The Sanford Project. “It has taken a tremendous amount of work from a large team to get this far. We still have another year of follow-up before we can really see how this treatment may be working.”

Griffin and Fargo-based pediatric endocrinologist Luis Casas, M.D., are the study’s principal investigators at Sanford Health.

Individuals with type 1 diabetes experience a loss of insulin-producing beta cells as their immune system targets these cells inappropriately. Treg cells usually keep the immune system under control, but they are lacking in number and activity in people with type 1 diabetes. The Sanford Project: T-Rex Study is exploring whether expanding the body’s supply of Treg cells can rebalance the immune system, stop destruction of beta cells and preserve insulin production. Participants were randomized to either of two doses in the treatment arms or to placebo. For those in the treatment groups, the participant’s own Treg cells were extracted from the body, purified, expanded in culture, and returned to blood circulation. The cell identification and expansion process is patented technology licensed by Caladrius, a cell-therapy development company.

The therapy being used in this trial, CLBS03, has received fast track designation from the U.S. Food and Drug Administration (FDA), a first for any type 1 diabetes intervention. That designation is reserved for drugs or biologics that address a serious health condition, like type 1 diabetes, where there is an unmet medical need. This status allows for more frequent communication with the FDA and faster feedback about the therapy during the approval process. It also allows researchers to submit data and reports on a rolling basis. CLBS03 also has been granted European Medicines Agency’s Advanced Therapeutic Medicinal Product classification and FDA Orphan Drug designation as a potential new treatment for recent-onset T1D.

The Sanford Project is a cornerstone initiative at Sanford Health focusing on finding a cure for type 1 diabetes. The initiative was launched as part of a $400 million gift from philanthropist Denny Sanford in 2007.

About Caladrius Biosciences

Caladrius Biosciences, Inc. is a clinical stage biopharmaceutical company with multiple technology platforms targeting autoimmune and select cardiology indications. The Company is investigating its lead product candidate, CLBS03, an ex vivo expanded polyclonal T regulatory cell therapy for the treatment of recent-onset type 1 diabetes, in an ongoing Phase 2 trial. CLBS14, CD34+ cell therapy intended as a treatment for coronary microvascular dysfunction, is Caladrius’ proprietary and patent protected formulation of CD34 cells designed specifically to enhance the potency of the CD34 cells for repair and regeneration of cardiovascular tissue. Its companion product, CLBS12, is specifically formulated for intramuscular administration for the treatment of lower extremity ischemia. A phase 2 study of CLBS12 as a treatment for critical limb ischemia has initiated in Japan, a successful outcome of which will qualify the program for consideration of early conditional approval based on discussions with the Japanese regulatory authorities as provided for under Japan’s progressive regenerative medicine regulations. For more information about Caladrius please visit http://www.caladrius.com.

About Sanford Health

Sanford Health is one of the largest health care systems in the nation, with 44 hospitals and nearly 300 clinics in nine states and four countries. Headquartered in Sioux Falls, South Dakota, and serving the Upper Midwest, with nearly 1,400 physicians, Sanford Health is dedicated to several initiatives, including global clinics, genomic medicine and specialized centers researching cures for type 1 diabetes, breast cancer and other diseases. Sanford Health has 28,000 employees, making it the largest employer in the Dakotas. Nearly $1 billion in gifts from philanthropist Denny Sanford over the past decade have transformed how Sanford Health can improve the human condition. For information, visit sanfordhealth.org.

SOURCE: www.eurekalert.org/pub_releases

Celgene reveals strong P3 Otezla data in rare inflammatory condition

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Celgene has lifted the curtain on strong new Phase 3 data for its phosphodiesterase 4 (PDE4) inhibitor Otezla (apremilast) in the treatment of Behçet’s disease, a rare immune condition characterised by a wide range of symptoms as a result of blood vessel inflammation.

Drawn from a study of 207 patients to determine the drug’s efficacy in the treatment of oral ulcers brought on by the disease, the data was presented at the 2018 American Academy of Dermatology (AAD) Annual Meeting. It was found that Otezla demonstrated “statistically significant reductions in oral ulcers” compared to placebo after 12 weeks of treatment, according to the area under the curve (AUC), which assesses the change in number of recurrent oral ulcers over time.

Additionally, Celgene reported that “statistically significant” improvements were seen in the trial’s secondary endpoints, including oral ulcer pain, overall disease activity and quality of life.

“The positive phase III findings in Behçet’s Disease reflect the unique aspects of the profile of Otezla 30 mg across inflammatory-related diseases,” commented Terrie Curran, President, Celgene Inflammation and Immunology. “Otezla 30 mg has the potential to provide a clinically meaningful new treatment option for patients and doctors and to become the first product indicated specifically for the treatment of active Behçet’s Disease with oral ulcers.”

Symptoms of Behçet’s disease can include recurrent oral and genital ulcers, skin lesions, arthritis, vasculopathy and uveitis. The root cause of the condition is unknown.

“Reducing oral ulcers, which are painful and can negatively impact quality of life, is an important goal in the treatment of people with Behçet’s syndrome,” added Dr Gulen Hatemi, Associate Professor, Istanbul University Cerrahpassa Medical School. “These findings suggest that apremilast, which reduced oral ulcers and oral ulcer pain, and improved disease activity in this pivotal study, has the potential to be a treatment option for patients with active Behçet’s syndrome with oral ulcers, for which few treatment alternatives exist.”

SOURCE: www.pharmafile.com/news/516584

Merck Foundation and Uganada Ministry continue support Heroines of ‘Merck More Than A Mother’

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Merck Foundation, a non-profit organization and a subsidiary of Merck KGaA Germany, and Uganda Ministry of Health continue their commitment towards childless women Through ‘Merck More Than a Mother’ campaign in the heart of Africa.

Merck Foundation evaluated the social and economic impact of ‘Merck More Than a Mother’ on childless women in Uganda and encouraged them to continue leading an independent and happier life.

In 2016, Merck Foundation in partnership with Uganda Ministry of Health had started ‘Merck More Than a Mother’ Campaign In the country with the aim to raise awareness about infertility prevention and management, build fertility care capacity and break the stigma around infertile women. They established various income generating projects to support infertile women across the country with the aim of empowering them socially and economically. The business set by Merck Foundation has benefitted over 800 women across Uganda.

“The childless women groups we created in each village are doing a great job. I remember last year they had no purpose in life, no respect from their community and no source of income. Today they have a bank account and a steady monthly income; now they are much happier and stronger,” said Rasha Kelej, CEO Merck Foundation.

“For me, it’s essential to frequently visit ‘Merck More Than a Mother’ heroines across Africa to influence their transformation. The base of change in these villages is remarkable, and with our efforts and passion this change will be sustainable,” she added.

“The journey that Merck Foundation has started is a very special journey that has touched the lives of women who have been forgotten in the communities. It has touched not only women but also the lives of men who have been mistreating their women thinking that infertility is an issue of women, not know that 50% infertility is due to the malefactor. I want to thank Merck Foundation for thinking about these women,” said Sarah Opendi, Minister of State of Health, Uganda.

“I feel grateful and honored to be a part of the joy and happiness of these amazing women, who suffered the infertility stigma all their lives. I am glad that the efforts of ‘Merck More Than a Mother’ paid off. Now, these women are independent and getting the respect and support they deserved from the community,” said Kelej.

About ‘Merck More Than a Mother’ campaign; in many cultures, childless women suffer discrimination, stigma, and ostracism. Their inability to have children results in great isolation, disinheritance, and assaults. ‘Merck More Than a Mother’ empowers such women through the access to information, health, change of mindsets and economic empowerment.

Merck Foundation provided for more than 40 candidates, three months to six months clinical and practical training for fertility Specialists and embryologists in more than 15 countries across Africa and Asia.

Merck Foundation is making history in many African countries where they never had fertility specialists or training facilities before ‘Merck More Than a Mother’ intervention to train the first Fertility specialists such as; in Sierra Leone, Liberia, The Gambia, Niger, Chad, and Guinea.

Merck Foundation plan supported the establishment of the first public IVF in Ethiopia through providing the clinical and practical training necessary for their staff. Merck Foundation also plans to support the establishment of the first public IVF in Tanzania soon.

Over 1,200 infertile women in Kenya, Uganda, Nigeria, Ghana, Tanzania, CAR, Ethiopia, Liberia, Tanzania, Niger, The Gambia and Cote D’Ivoire who can no longer be treated have been empowered socially and economically to lead independent and happier lives through “Empowering Berna”.(ANI)

SOURCE: www.aninews.in/news/business/business

Psoriasis drug found to reduce aortic vascular inflammation

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An antibody used to treat the skin disease psoriasis is also effective at reducing aortic inflammation, a key marker of future risk of major cardiovascular events.

An antibody used to treat the skin disease psoriasis is also effective at reducing aortic inflammation, a key marker of future risk of major cardiovascular events.

Researchers from the Perelman School of Medicine at the University of Pennsylvania, in collaboration with the National Heart, Lung, and Blood Institute, led a randomised, double-blind, placebo-controlled study and found patients who took the drug ustekinumab had a 19 percent improvement in aortic inflammation, as measured and confirmed by imaging, when compared to the placebo group. Dr Joel M. Gelfand, a Professor of Dermatology and Epidemiology at Penn and the study’s first author.

Ustekinumab, sold under the name Stelara, is approved by the US Food and Drug Administration to treat psoriasis, psoriatic arthritis, and Crohn’s Disease. Researchers wanted to know if the benefits of the drug go beyond clearing the skin.

“The type of inflammation we see in psoriasis is similar to what we see in atherosclerosis – a type of heart disease that involves the build-up of fats, cholesterol, and inflammatory cells in the artery walls,” Dr Gelfand said. “Since ustekinumab blocks the specific pathways involved in both skin and cardiovascular inflammation, we wanted to test whether it can improve aortic vascular inflammation.”

Psoriasis patients were randomly divided into two groups, with 21 patients in the placebo group and 22 patients receiving the treatment. The primary outcome was aortic inflammation, as measured by 18-FDG-PET/CT scans – an imaging technique that reveals inflammation in the aorta. The imaging was performed before treatment and at 12 weeks. The treatment group saw a 6.6 percent decrease in aortic inflammation, while the placebo group saw a 12 percent increase, meaning the drug is responsible for a 19 percent improvement relative to untreated patients. As expected, ustekinumab also resulted in a dramatic improvement in skin inflammation as well, with 77 percent of treated patients achieving a 75 percent or better improvement in psoriasis activity, compared to just 10.5 percent in the placebo group. Both findings were highly statistically significant (p?0.001).

The results are consistent with a previous, smaller uncontrolled trial of ustekinumab, but they are in direct contrast to two large trials using a different drug called adalimumab, which is sold as Humira.

“This is the first placebo-controlled trial of a biologic drug to show a benefit in aortic inflammation, a key marker of cardiovascular disease,” Dr Gelfand said. “The effect is similar to what we would expect if we put the patient on a statin.”

Dr Gelfand, who conducted the study in collaboration with Dr Nehal N. Mehta, Chief of the Section of Inflammation and Cardiometabolic Diseases at the National Heart, Lung, and Blood Institute, confirmed their results by having a second, separate lab independently evaluate imaging data.

“This study represents a promise that this treatment may reduce the risk of heart attack and stroke in the future. It’s an encouraging finding,” Dr Gelfand said.

The trial is ongoing, and Dr Gelfand says his team will evaluate these patients at a longer follow up to see if the effects are sustainable and if patients continue to improve.

SOURCE: www.europeanpharmaceuticalreview.com/news/72839

AZ bags key lung cancer approval for Imfinzi

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Becomes the first PD-1/PD-L1 inhibitor approved to treat inoperable stage III NSCLC patients

AstraZeneca has secured FDA approval for its checkpoint inhibitor Imfinzi in non-small cell lung cancer, opening up a big potential market for the drug as it chases the leaders in the cancer immunotherapy sector.

PD-L1 inhibitor Imfinzi (durvalumab) was approved by the US regulator just ahead of the weekend as a maintenance therapy for NSCLC patients with inoperable stage III disease, ie that has not spread widely around the body after platinum chemotherapy or radiotherapy.

AZ’s drug is the first PD-1/PD-L1 inhibitor to be approved for this indication and according to analysts it could kickstart sales of the drug in a market segment according to analysts could unlock up to $2bn in additional sales for the drug. The FDA granted the drug a breakthrough designation in non-metastatic NSCLC last July.

Before now Imfinzi was only approved for bladder cancer – where it has to compete head-to-head with other checkpoint inhibitors including Bristol-Myers Squibb’s Opdivo (nivolumab) and Merck & Co/MSD’s Keytruda (pembrolizumab) – so the new indication should inject some sales momentum. In 2017 AZ recorded $19m in sales of the drug – $18m in the fourth quarter – so it has a long way to go to catch its blockbuster rivals, but has a couple of year’s head start in the new indication.

The approval is based on the results of the PACIFIC trial, which showed that patients treated with Imfinzi gained an extra 11 months of progression-free survival (PFS) compared to placebo. Patients on AZ’s drug had a PFS of 16.8 months, compared to 5.6 months in the control group. The benefits were seen across all patient subgroups, regardless of PD-L1 status, and AZ’s drug was also associated with a lower incidence of metastasis.

“The approval of Imfinzi in this earlier stage of NSCLC is a truly meaningful milestone for patients who, until now, had no FDA-approved treatment options following chemoradiation therapy,” commented Dave Fredrickson, head of AZ’s cancer business unit.

“Globally, approximately 30% of patients with NSCLC present with stage III disease and we are excited to launch the first immunotherapy into this setting.”

Looking ahead to the next few months, AZ is also waiting for data read-outs from the ARCTIC trial of Imfinzi plus its CTLA4 inhibitor tremelimumab in third-line NSCLC, final overall survival data from the MYSTIC trial in first-line NSCLC (after disappointing progression-free survival results) looking at the combination as well as Imfinzi on its own, and results of the NEPTUNE trial of the Imfinzi plus tremelimumab in first-line NSCLC.

AZ is also expecting read-outs from The KESTREL and EAGLE trials of Imfinzi with and without tremelimumab in head and neck cancer.

SOURCE: www.pmlive.com/pharma_news

AbbVie reports more solid data for would-be psoriasis blockbuster

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AbbVie thinks it could have a best-in-class immunotherapy drug with its interleukin-23 blocker risankizumab, and updated results in psoriasis won’t undermine that view.

A pair of phase III trials pitting risankizumab against Johnson & Johnson’s older IL-12/IL-23 inhibitor Stelara (ustekinumab) – reported at the American Academy of Dermatology meeting in Chicago over the weekend – found that it was much more likely to clear skin in patients with moderate to severe plaque psoriasis.

The new drug will need to show stellar efficacy if it is to make headway in the increasingly crowded psoriasis market, and the results from the ultIMMa-1 and ultIMMa-2 seem to keep it on track. The data reveal a superior profile to Stelara as an active control, with up to 60% of patients on the drug reporting clear skin after a year compared to 21%-30% with Stelara.

AbbVie’s drug is in hot pursuit of the only approved IL-23 inhibitor on the market – J&J’s Tremfya (guselkumab) – and some analysts including Leerink’s Geoffrey Porges have suggested trials to date show risankizumab might be a little better than its rival with the potential for less frequent dosing.

Its profile could also help it make headway against other new psoriasis drugs, including IL-17 inhibitors such as Novartis’ fast-growing Cosentyx (secukinumab) as well as Eli Lilly’s Taltz (ixekizumab) and Valeant’s Siliq (brodalumab).

New drugs are starting to chip away at the dominance of AbbVie’s anti-TNF drug Humira (adalimumab) in psoriasis and other indications like rheumatoid arthritis, although it still dwarfs them with sales of more than $18bn last year and remains the world’s biggest-selling pharma product.

Risankizumab’s data could propel it above the $1bn threshold in psoriasis alone, according to Leerink, with additional upside if it gets approved in other indications such as psoriatic arthritis and Crohn’s disease.

Meanwhile, AbbVie also reported positive phase IIb results with its new oral JAK1 inhibitor upadacitinib – another drug considered to a key pipeline prospect and potential blockbuster – in adults with moderate to severe atopic dermatitis (eczema) at the AAD.

The latest data, updating earlier results reported last year, showed that upadacitinib was able to significantly reduce the itch associated with atopic dermatitis after just one week and improved the extent and severity of skin lesions at week two.

Upadacitinib is vying to become the third drug in the class after Pfizer’s Xeljanz (tofacitinib) and Eli Lilly’s Olumiant (baricitinib) as a rheumatoid arthritis treatment, reporting encouraging phase III data last year, and is also in pivotal trials for psoriatic arthritis and Crohn’s disease.

AbbVie now says it plans to begin pivotal studies in atopic dermatitis, as well as ulcerative colitis and giant cell arteritis before the end of the year. Upadacitinib (also known as ABT-494) has been tipped by some analysts as a future leader of the JAK inhibitor category with sales of up to $3.5bn at peak.

SOURCE: http://www.pmlive.com/pharma_news

TB vaccine trial results offer potential for BCG revaccination

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Study is the first ‘prevention of infection’ trial conducted for tuberculosis, the world’s leading infectious disease killer.

Aeras, a nonprofit organisation dedicated to developing vaccines against tuberculosis (TB), has announced results from an innovative clinical trial that provides encouraging new evidence that TBvaccines could prevent sustained infections in high-risk adolescents.

In a prevention-of-infection Phase 2 trial conducted in South Africa, revaccination with the Bacille Calmette-Guerin (BCG) vaccine significantly reduced sustained TB infections in adolescents. An experimental vaccine candidate, H4:IC31, also reduced sustained infections, although not at statistically significant levels. However, the trend observed for H4:IC31 is the first time a subunit vaccine has shown any indication of ability to protect against TB infection or disease in humans.

TB infections that developed during the study were determined using a QuantiFERON-TB Gold in Tube (QFT-GIT) test, a commercially available blood test that helps diagnose TB infections. In the trial, individuals who tested negative for QFT-GIT were considered to not have a TB infection. The trial measured the rate by which individuals converted to QFT-GIT positive, implying evidence of TB infection. Those individuals who tested QFT-GIT positive consecutively over 6 months were considered to have a sustained infection.

According to the World Health Organization (WHO), about one-third of the world’s population has what is called a latent TB infection, which means people have been infected by TB bacteria but are not (yet) ill with the disease and cannot transmit the disease. People infected with TB bacteria have a lifetime risk of falling ill with TB of 10 percent. People ill with TB can infect 10-15 other people through close contact over the course of a year. Without proper treatment, 45% of HIV-negative people with TB on average and nearly all HIV-positive people with TB will die.

Dr Mark Hatherill, Director of the South African Tuberculosis Vaccine Initiative (SATVI) at the University of Cape Town, and the study’s principal investigator, said: “We are pleased to have performed the first-known randomised, placebo-controlled prevention-of-infection trial for TB and to have demonstrated that vaccination has the potential to reduce the rate of sustained TB infection in a high-transmission setting. While neither vaccine proved to be statistically significant in preventing an initial TB infection, we are extremely encouraged by the signals observed for both vaccines in preventing sustained TB infections. We believe the results from this novel trial design will provide significant scientific benefit to the field in understanding TB infection, and based on this positive signal, we look forward to testing the potential of such vaccines to prevent TB disease among uninfected adolescents in a larger, more traditional prevention-of-disease clinical trial.”

The study evaluated H4:IC31 vaccination and BCG revaccination for safety, immunogenicity and the ability to prevent initial and sustained TB infections among healthy adolescents in the Western Cape Province of South Africa. H4:IC31 is an investigative subunit vaccine candidate being developed jointly by Aeras and Sanofi Pasteur, the vaccines business of Sanofi (EURONEXT: SAN) (NYSE: SNY), and the Statens Serum Institut. BCG is the only licensed tuberculosis vaccine available globally. The clinical trial was conducted at SATVI and at the Emavundleni Research Centre (part of the Desmond Tutu HIV Centre). It was funded by Sanofi Pasteur, the United Kingdom’s Department for International Development, and Aeras. The study was approved by the Medicines Control Council of South Africa and the relevant local independent ethics committees.

Dr Linda-Gail Bekker, a lead investigator for the trial, the Chief Operating Officer at the Desmond Tutu HIV Foundation and President of the International AIDS Society, said: “We would like to thank all the study participants and their families for participating in this novel clinical trial. We believe the results are important and warrant further investigation into other subunit vaccines and a reevaluation of BCG revaccination as a potential strategy to prevent TB in high-incidence countries. An effective TB vaccine remains an urgent global goal.”

Dr Jacqui Shea, CEO of Aeras, stated: “New TB vaccines are essential to end this deadly epidemic, especially with the rise of drug-resistant strains. In this innovative study, we not only observed important results for BCG, we also saw the first early efficacy signal against infection to be shown by a subunit TB vaccine candidate (H4:IC31). Further, we established that the novel prevention-of-infection trial design has the potential to provide evidence of a biological signal earlier and at lower cost than traditionally designed TB vaccine prevention of disease efficacy studies. The data collected will inform the next series of clinical studies as well as enable the search for correlates of protection against sustained infection. Later this year, Aeras and its partners look forward to announcing primary results from a Phase 2b prevention of disease trial with M72/AS01E, another subunit vaccine candidate, and to commencing two Phase 2 clinical trials with an additional, promising subunit vaccine candidate.”

The study involved 990 HIV-negative, healthy adolescents (12 to 17 years of age) who had been vaccinated as infants with BCG. All participants were randomised evenly into three study arms: placebo, H4:IC31, or BCG revaccination. All participants were screened to ensure they were not infected with Mycobacterium tuberculosis (Mtb) prior to vaccination in the study. At the outset of this innovative proof-of-concept study, statistical significance was set at one-sided p<0.1 to favor the risk of observing a false positive efficacy signal rather than a false negative.

The data showed that both vaccines appeared to be safe and produced an immune response in the adolescents studied. No vaccine-related serious adverse events were reported in the study, and the most common vaccine-related adverse event was injection site swelling in BCG revaccinated participants, typical for BCG vaccination.

For the primary efficacy endpoint, 134 participants tested positive for an initial Mtb infection as measured by QFT-GIT conversion from negative to positive (placebo=49; BCG=41; H4:IC31=44). When compared to placebo, neither vaccine achieved statistical significance in preventing an initial QFT-GIT conversion. Observed vaccine efficacy was 20.1% (p=0.15) for BCG revaccination and 9.4% (p=0.32) for H4:IC31.

For the secondary efficacy endpoint, 82 participants exhibited a sustained QFT-GIT conversion lasting at least 6 months following initial conversion (placebo=36; BCG=21; H4:IC31=25). These participants were evaluated to see if they would revert to negative as measured by the QFT-GIT test. In the BCG revaccination arm, the vaccine efficacy for preventing a sustained infection was 45.4% (p=0.013) and in the H4:IC31 arm the vaccine efficacy was 30.5% (p=0.08).

SOURCE: www.europeanpharmaceuticalreview.com/news/72847