FDA Approves Kalydeco (ivacaftor) for Cystic Fibrosis in Children Ages 12 to <24 Months with Certain Mutations in the CFTR Gene

BOSTON–(BUSINESS WIRE)–Aug. 15, 2018– Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the U.S. Food and Drug Administration (FDA) approved Kalydeco (ivacaftor) to include use in children with cystic fibrosis (CF) ages 12 to <24 months who have at least one mutation in their cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Kalydeco based on clinical and/or in vitro assay data.

“Cystic fibrosis is a chronic, progressive disease that is present at birth, with symptoms often occurring in infancy,” said Reshma Kewalramani, M.D., Executive Vice President and Chief Medical Officer at Vertex. “With today’s approval, parents and physicians now have a medicine to treat the underlying cause of CF in patients as young as one year of age. We are excited about the progress of our portfolio and continue to support additional research on the potential benefit of early intervention with all of our medicines, with the goal of bringing a treatment to all people living with CF.”

This FDA approval is based on data from the ongoing Phase 3 open-label safety study (ARRIVAL) of 25 children with CF aged 12 to <24 months who have one of 10 mutations in the CFTR gene (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H). The study demonstrated a safety profile consistent with that observed in previous Phase 3 studies of older children and adults; most adverse events were mild or moderate in severity, and no patient discontinued due to adverse events. Two patients had elevated liver enzymes greater than eight times the upper limit of normal, but continued to receive Kalydeco after a dose interruption. The most common adverse events (≥30%) were cough (74%), pyrexia (37%), elevated aspartate aminotransferase (37%), elevated alanine aminotransferase (32%) and runny nose (32%). Four serious adverse events were observed in two patients.

Mean baseline sweat chloride for the children in this study was 104.1 mmol/L (n=14). Following 24 weeks of treatment with Kalydeco, the mean sweat chloride level was 33.8 mmol/L (n=14). In the 10 subjects with paired sweat chloride samples at baseline and week 24, there was a mean absolute change of -73.5 mmol/L. These data were presented at the 41stEuropean Cystic Fibrosis Society (ECFS) Conference in June 2018 and published in The Lancet Respiratory Medicine (Volume 6, No 7, July 2018).

“I’m very excited about the approval of ivacaftor in children ages 12 to less than 24 months as this is the first regulatory approval of a CFTR modulator in this age group,” said Margaret Rosenfeld, M.D., MPH, Seattle Children’s Research Institute and Department of Pediatrics, University of Washington School of Medicine. “The premise of newborn screening for CF is to intervene very early in the course of disease with the goal of improving long term outcomes, so this is a significant milestone for parents and caregivers of young children with CF.”

Kalydeco was already approved in the U.S. for the treatment of CF in patients ages 2 and older who have one of 38 ivacaftor-responsive mutations in the CFTR gene based on clinical and/or in vitro assay data. Vertex submitted a Marketing Authorization Application for a line extension (ages 12 to <24 months) to the European Medicines Agency with a decision anticipated in the first half of 2019.

About Cystic Fibrosis

Cystic Fibrosis (CF) is a rare, life-shortening genetic disease affecting approximately 75,000 people in North America, Europe and Australia.

CF is caused by a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF. There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test, or genotyping test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the mid-to-late 20s.

About Kalydeco (ivacaftor)

Kalydeco (ivacaftor) is the first medicine to treat the underlying cause of CF in people with specific mutations in the CFTR gene. Known as a CFTR potentiator, Kalydeco is an oral medicine designed to keep CFTR proteins at the cell surface open longer to improve the transport of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways. Kalydeco is available as 150 mg tablets for adults and pediatric patients age 6 years and older, and is taken with fat-containing food. It is also available as 50 mg and 75 mg granules in pediatric ages 12 months to less than 6 years and is administered with soft-food or liquid with fat-containing food.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious and life-threatening diseases. In addition to clinical development programs in CF, Vertex has more than a dozen ongoing research programs focused on the underlying mechanisms of other serious diseases.

Founded in 1989 in Cambridge, Mass., Vertex’s headquarters is now located in Boston’sInnovation District. Today, the company has research and development sites and commercial offices in the United States, Europe, Canada and Australia. Vertex is consistently recognized as one of the industry’s top places to work, including being named to Science magazine’s Top Employers in the life sciences ranking for eight years in a row. For additional information and the latest updates from the company, please visit www.vrtx.com.

Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)

Vertex initiated its CF research program in 2000 as part of a collaboration with CFFT, the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Kalydeco® (ivacaftor), ORKAMBI®(lumacaftor/ivacaftor), SYMDEKO® (tezacaftor/ivacaftor and ivacaftor), VX-659 and VX-445 were discovered by Vertex as part of this collaboration.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, the statements in the second and fifth paragraphs of the press release and statements regarding the Marketing Authorization Application for a line extension submitted to the European Medicines Agency. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company’s beliefs only as of the date of this press release and there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company’s development programs may not support registration or further development of its compounds due to safety, efficacy or other reasons, and other risks listed under Risk Factors in Vertex’s annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company’s website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

Source: Vertex Pharmaceuticals Incorporated

Posted: August 2018

Related Articles:

  • FDA Approves Kalydeco (ivacaftor) for People Ages 2 and Older With Cystic Fibrosis Who Have Certain Residual Function Mutations – August 1, 2017
  • FDA Expands Approved Use of Kalydeco to Treat Additional Mutations of Cystic Fibrosis – May 17, 2017
  • FDA Approves Kalydeco (ivacaftor) for Cystic Fibrosis in Children Ages 2 to 5 with CFTR Gene Mutations – March 18, 2015
  • FDA Approves Kalydeco (ivacaftor) for Use in People with Cystic Fibrosis Ages 6 and Older Who Have the R117H Mutation – December 29, 2014
  • FDA Approves Kalydeco to Treat Rare Form of Cystic Fibrosis – January 31, 2012
  • FDA Grants Priority Review for Kalydeco (ivacaftor), the First Potential Medicine to Target the Underlying Cause of Cystic Fibrosis – December 15, 2011
  • Vertex Submits Application for Priority Review and Approval of Kalydeco (VX-770, ivacaftor) in the U.S. as First Potential Medicine to Target the Underlying Cause of Cystic Fibrosis – October 26, 2011

Kalydeco (ivacaftor) FDA Approval History

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7 Natural Remedies to Help You Breeze Through PMS

The Curse. Aunt Flow. Mother Nature’s Monthly Gift.

Whatever you call it, you’re probably not thrilled with it. Legendary country singer Dolly Parton even wrote a song about it. She called it “PMS Blues,” singing, “I got those God almighty, slap somebody PMS blues….” (Check it out on YouTube if you like.)

Premenstrual syndrome is the official name for everything women go through before their monthly menstrual period stars, with some of those symptoms continuing on through the cycle. For many, though, “syndrome” doesn’t quite describe it.

Instead, it’s more like a condition, an illness, or something akin to the flu. Many women just plain don’t feel good, don’t feel like themselves, and wish the time would go by as quickly as possible.

It may help some to laugh about it. After all, it does happen once a month, generally, and women have to deal with it. But for many, it’s no laughing matter, and finding solutions is critical to being able to go about their normal lives.

What Is PMS?

Premenstrual syndrome (PMS) is considered a medical condition that affects women of childbearing age. Definitions usually describe it as a predictable set of disturbing physical and emotional symptoms that occur in relationship to the menstrual period, typically in the one-to-two weeks leading up to it.

Physical symptoms may include the following:

  • Fatigue
  • Bloating
  • Breast tenderness
  • Headaches and migraines
  • Backaches
  • Acne flare-ups
  • Sleeping disturbances
  • Cramps
  • Food cravings

PMS can also cause emotional symptoms, including the following:

  • Irritability
  • Stress and anxiety
  • Depression
  • Mood swings
  • Difficulty concentrating
  • Crying spells

Doctors don’t know exactly what causes it. They understand it comes around as hormones change to prepare the female body for menstruation, but they’re not sure why some women seem to suffer more severe symptoms than others, or why the cycle can cause uncomfortable symptoms at all.

There are some theories that the hormonal changes may cause chemical changes in the brain that lead to symptoms of PMS, and that diet may also play a part in the severity of those symptoms.

What is PMDD?

Premenstrual dysphoric disorder (PMDD) is a more severe form of PMS, with symptoms that significantly disrupt a woman’s work, family, and social life. It affects only a small percentage of women—about three to eight percent, according to Hopkins Medicine.

In addition to the standard symptoms of PMS, women suffering from PMDD may also suffer from nausea and vomiting, fainting, heart palpitations, muscle spasms, painful menstruation, edema, breast pain, and more. Psychological symptoms may include depression, paranoia, emotional hypersensitivity, lack of personal control, anger, and confusion.

Treatments for PMDD often include antidepressants, birth control pills (which stabilize hormonal changes), nutritional supplements, and herbal remedies. Most doctors recommend women get help, as the symptoms tend to get worse with age, not better, until menopause.

Standard Treatments for PMS

If you go to see your doctor about PMS, likely he’ll suggest you start with lifestyle changes, such as making sure you get regular exercise, limit salty foods, and avoid caffeine and alcohol.

If you still suffer from serious symptoms, however, your doctor is likely to suggest one or more of the following:

  • Birth control pills: This is a popular solution for PMS, as it helps balance hormones, which can significantly reduce symptoms. Plus, it’s a low-risk option for most women, and something many need during their childbearing years anyway.
  • Natural progesterone cream: Some women may not find relief with birth control pills, or may find that pills actually make their symptoms in worse. Natural progesterone may work better in these cases. Progesterone can help balance menstrual hormone levels, which can help reduce symptoms.
  • Antidepressants: Women who are suffering from emotional/psychological symptoms may best benefit from antidepressants. These can help balance out the neurotransmitters in the brain, reducing mood swings and irritability.
  • Pain-relieving drugs: Over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin can help relieve cramps, joint pain, headaches, and breast pain.
  • Diuretics: Women who suffer from bloating, edema, and weight gain may benefit most from these water pills, which help the body to flush more water out during the PMS period.

7 Natural Treatments for PMS

Some women may not find enough relief with the above remedies, or may want to avoid potential side effects with more natural approaches. Fortunately, there are seven that have been shown in studies to provide significant relief.

Some women report relief with herbal supplements like black cohosh, ginkgo biloba, evening primrose, chasteberry, St. John’s wort, but so far, we don’t have enough quality study results to know for sure. If none of the above treatments help, herbal remedies may be worth a try!

 

Sources

Mayo Clinic Staff, “Premenstrual syndrome (PMS),” Mayo Clinic,  December 16, 2014, http://www.mayoclinic.org/diseases-conditions/premenstrual-syndrome/basics/definition/con-20020003.

 

“Premenstrual syndrome (PMS) fact sheet,” Women’s Health, U.S. Department of Health and Human Services, http://www.womenshealth.gov/publications/our-publications/fact-sheet/premenstrual-syndrome.html.

 

“Premenstrual Dysphoric Disorder (PMDD),” Hopkins Medicine, http://www.hopkinsmedicine.org/healthlibrary/conditions/gynecological_health/premenstrual_dysphoric_disorder_pmdd_85,P00580/.

 

Laura Johannes, “Does Calcium Lessen the Symptoms of PMS?” Wall Street Journal, December 16, 2008, http://www.wsj.com/articles/SB122937831273108391.

 

Thys-Jacobs S., et al., “Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group,” Am J Obstet Gynecol., August 1998; 179(2):444-52, http://www.ncbi.nlm.nih.gov/pubmed/9731851.

 

Facchinetti F., et al., “Oral magnesium successfully relieves premenstrual mood changes,” Obstet Gynecol., August 1991; 78(2):177-81, http://www.ncbi.nlm.nih.gov/pubmed/2067759.

 

Quaranta S., et al., “Pilot study of the efficacy and safety of a modified-release magnesium 250 mg tablet (Sincromag) for the treatment of premenstrual syndrome,” Clin Drug Investig., 2007; 27(1):51-8, http://www.ncbi.nlm.nih.gov/pubmed/17177579.

 

“Magnesium,” University of Maryland Medical Center, August 6, 2015, https://umm.edu/health/medical/altmed/supplement/magnesium.

 

Finoa Macrae, “Vitamin E pill ‘eases pain of PMS by up to two-thirds,’” Daily Mail, January 17, 2011, http://www.dailymail.co.uk/health/article-1347812/Vitamin-E-pill-eases-pain-PMS-thirds.html.

 

Edilberto A Rocha Filho, et al,. “Essential fatty acids for premenstrual syndrome and their effect on prolactin and total cholesterol levels: a randomized, double blind, placebo-controlled study,” Reprod Health, 2011; 8:2, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033240/.

 

Sohrabi N, et al., “Evaluation of the effect of omega-3 fatty acids in the treatment of premenstrual syndrome: ‘a pilot trial,’” Complement Ther Med., June 2013; 21(3):141-6, http://www.ncbi.nlm.nih.gov/pubmed/23642943.

 

Wu WL, et al., “The acute effects of yoga on cognitive measures for women with premenstrual syndrome,” J Altern Complement Med., June 2015; 21(6):364-9, http://www.ncbi.nlm.nih.gov/pubmed/25965108.

 

Dvivedi J, et al., “A Study of the Effects of Training of 61-Point Relaxation in Women Suffering from Stress of Premenstrual Syndrome,” J Yoga Phys Therapy, 1:106, http://www.omicsonline.org/a-study-of-the-effects-of-training-of-61-point-relaxation-in-women%20suffering-from-stress-of-premenstrual-syndrome-2157-7595.1000106.pdf.

 

S-Y Kim, et al., “Acupuncture for premenstrual syndrome: a systematic review and meta-analysis of randomized controlled trials,” BJOG, 2011; 118:899-915, http://onlinelibrary.wiley.com/store/10.1111/j.1471-0528.2011.02994.x/asset/j.1471-0528.2011.02994.x.pdf;jsessionid=EF6125C7F869F73E506387E67F47F890.f01t03?v=1&t=ienaedcx&s=f83f06dcfe1cad1900c1496a95d2a18a1b7ea1cf.

 

Sniezek DP, Siddiqui IJ, “Acupuncture for treating anxiety and depression in women: a clinical systematic review,” Medical Acupuncture, 2013; 25(3):164-172, http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0058508/.

 

Danno K, et al., “Homeopathic treatment of premenstrual syndrome: a case series,” Homeopathy, January 2013; 102(1):59-65, http://www.ncbi.nlm.nih.gov/pubmed/23290881.

 

Yakir M., et al., “Effects of homeopathic treatment in women with premenstrual syndrome: a pilot study,” Br Homeopath J., July 2001; 90(3):148-53, http://www.ncbi.nlm.nih.gov/pubmed/11479782.

 

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Thomas Rhett's Baby Turns 1, & the Pics Are Beyond

What’s a first birthday without a grubby, happy, cake-covered baby? Thankfully, country singer Thomas Rhett has some photos that fit the bill, as his little girl, Ada James, looks like she dove into her birthday cake face-first. 

It looks like Ada really enjoyed her Coco-themed birthday cake. The dark blue frosting totally got everywhere, including her face (of course), her fancy white shirt that says, "One," and her white high chair… even the seat. She looks pretty pleased with the whole situation, with her sparkly "1" birthday hat on her head and a huge, cake-fueled smile on her face. 

Thomas Rhett’s family is just more adorable with each Instagram shot he posts (I mean, check out this amazing matching swimsuit shot!). The couple adopted their older daughter, Willa Gray, from Uganda, and it was during the lengthy adoption process that his wife, Lauren Akins, discovered she was pregnant. In fact, it was during her third trimester that the adoption went through. Akins had to fly home to get a checkup, but Akins’ mom and dad were able to bring Willa home to her new parents. 

Let’s hope these parents continue to post super-charming photos of the girls as they grow. While Ada may not be smashing her face into a birthday cake when she’s a teenager, these treasured family photos are certainly something to look forward to — and look back on — as the years go by. 

Rhett told People, "Before you become a dad, you talk to other dads and moms and everybody is like, ‘Dude, soak it in because it’s going to go fast. And somebody told me this quote: ‘The days are long and the years are short.’ I don’t think you fully understand what that means until you have kids."

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Cerebral blood flow changes in pediatric patients with CKD

(HealthDay)—Pediatric patients with chronic kidney disease (CKD) have higher global cerebral blood flow (CBF) and regional differences in CBF, according to a study published recently in Radiology.

Hua-Shan Liu, Ph.D., from Taipei Medical University in Taiwan, and colleagues conducted a prospective study involving 73 pediatric patients with CKD and 57 control subjects. A magnetic resonance imaging arterial spin labeling scheme was used to acquire CBF measurements. Traditional and computerized neurocognitive batteries were used for neurocognitive measurements. Group-level global and regional CBF differences were compared between patients with CKD and controls.

The researchers found that, compared with control subjects, patients with CKD showed higher global CBF (mean, 60.2±9 versus 56.5±8 mL/100 g/min) that was attributable to reduced hematocrit level. There was a correlation between white matter CBF with blood pressure (r = 0.244; P = 0.039), which was indicative of altered cerebrovascular autoregulation. Regions in the default mode network were included in regional CBF differences between patients and control subjects. Positive extrema in the precuneus showed a strong correlation with executive function in patients with CKD.

“Systemic effects of estimated glomerular filtration rate, hematocrit level, and blood pressure on CBF and alterations in regional CBF may reflect impaired brain function underlying neurocognitive symptoms in CKD,” the authors write.

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The Best Baby Food Delivery Services

We all have the best intentions when it comes to feeding our kids. Maybe we start out promising to only serve them homemade, whole-food recipes made with organic and sustainably sourced ingredients… but then, reality hits, and we find ourselves giving them peanut butter (and not the kind from Whole Foods) on a spoon straight from the jar and calling it dinner. No judgment.

Enter baby food delivery services, which make providing super-healthy meals for your little ones not only possible but easy. These industry-disrupting companies all offer fresh, wholesome alternatives to the often preservative- and sugar-laden packaged goods you’ll find on grocery store shelves and ship them directly to your door. Most will even pick the menu for you based on your baby’s age and preferences so you truly don’t have to stress over any detail regarding your child’s nutrition.

Whether you have an infant just starting solids with purées or a toddler refusing to eat his veggies, there’s a company that caters to your tot’s developing palate. Click through to see the best options out there.

1
/6:
Little Spoon


1/6
:
Little Spoon

2
/6:
Yumi


2/6
:
Yumi

3
/6:
Nurture Life


3/6
:
Nurture Life

4
/6:
Yumble


4/6
:
Yumble

5
/6:
Pure Spoon


5/6
:
Pure Spoon

6
/6:
Raised Real


6/6
:
Raised Real

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Research eyes role of stress in mental illnesses

We all face stress in our lives. Even researchers seeking to understand why some people shrug it off while others face battles against disorders like depression or PTSD.

“I try to find the right balance in my life,” said Wataru Inoue, a Physiology and Pharmacology professor at the Schulich School of Medicine & Dentistry. “I’m so grateful to have this job because I enjoy it. Sometimes it’s stressful, I know. But we are chasing questions we don’t know the answers to. A great discovery from your research and all the stress goes away.”

Inoue explores “what our brains go through every day” – the biological mechanisms of how the brain deals with and adapts to stressful experiences. While current treatments and the progress in the development of new or improved drugs is slow, Inoue said advancing the understanding of stress neurobiology is a crucial step in identifying the key mechanisms causing mental illnesses and, ultimately, developing more effective treatment strategies.

His work hopes to provide answers and relief for the 13 per cent of Canadians and their families who deal with stress-related disorders. These issues are the fastest-growing category of disability insurance claims in Canada, costing an estimated $33 billion a year in lost productivity, as well as billions more in direct medical costs.

“When stress happens, it causes immediate changes. But, at the same time, we know it causes a long-lasting memory and those are important memories,” he said. “For example, when you have a bad experience, you want to remember that to avoid those things in the future. But, sometimes, those accumulations of memories can cause bad consequences which is perhaps part of the reason we do develop so much stress.”

Stress is necessary to guide us through our lives but can also have negative consequences, admitted Inoue, who wants to learn more about how stress causes memory formation and, subsequently, the resulting consequences.

“We need to remember those bad experiences. But maybe, in extreme conditions such as PTSD, it is a memory problem. You remember those traumatic experiences and they are so strong that it comes back all the time. So it actually causes more problems than benefits,” he said.

Inoue showed the progress of his research this week to London North MP Peter Fragiskatos and representatives from the Mental Health Research Association (MHRA), who provided financial backing for his ongoing work.

“It’s a very simple thing, but it didn’t occur to me that stress is something we only self-report on. Unless I raise my hand and say, ‘It’s overwhelming,’ there is no test,” said Andrea Swinton, CEO of MHRA, who is touring around the province to learn more about some of the research her organization is backing. “While some stress is good, what’s the tipping point to where it becomes dangerous? You never really think of stress as something that’s in your brain. I feel it in my gut, all over my body.

“This is very interesting work because my stakeholders are the 1-in-5 living with mental illness and those who live with and love them.”

Inoue said stress triggers a so-called ‘fight-or-flight’ response. This rapid defense mechanism involves coordinated changes in both psychological (i.e. fear, aggression) and physiological (i.e. release of stress hormone corticosteroids, elevation of heart rate) functions which, together, enhance the ability to handle impending challenges.

In addition to this immediate response, stress promotes associative learning that lasts beyond the stressful experience. In other words, we form a memory of a stressful episode and this memory reshapes the way we will respond to future challenges, he added.

Inoue focuses his work on the hypothalamus, the part of the brain that regulates hormonal response to stress. Stress-induced changes in this area may represent a key neurobiological mechanism for the abnormality of stress hormone levels and the changes in physiological behaviour, seen in many serious diseases.

“Why are those difference happening? Are they at the mechanistic level? We don’t know. We do have pieces of evidence. But it’s not all put together. That’s why we’re chasing after those questions. We know what we don’t know,” Inoue said.

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Researchers reverse congenital blindness in mice

Researchers funded by the National Eye Institute (NEI) have reversed congenital blindness in mice by changing supportive cells in the retina called Müller glia into rod photoreceptors. The findings advance efforts toward regenerative therapies for blinding diseases such as age-related macular degeneration and retinitis pigmentosa. A report of the findings appears online today in Nature. NEI is part of the National Institutes of Health.

“This is the first report of scientists reprogramming Müller glia to become functional rod photoreceptors in the mammalian retina,” said Thomas N. Greenwell, Ph.D., NEI program director for retinal neuroscience. “Rods allow us to see in low light, but they may also help preserve cone photoreceptors, which are important for color vision and high visual acuity. Cones tend to die in later-stage eye diseases. If rods can be regenerated from inside the eye, this might be a strategy for treating diseases of the eye that affect photoreceptors.”

Photoreceptors are light-sensitive cells in the retina in the back of the eye that signal the brain when activated. In mammals, including mice and humans, photoreceptors fail to regenerate on their own. Like most neurons, once mature they don’t divide.

Scientists have long studied the regenerative potential of Müller glia because in other species, such as zebrafish, they divide in response to injury and can turn into photoreceptors and other retinal neurons. The zebrafish can thus regain vision after severe retinal injury. In the lab, however, scientists can coax mammalian Müller glia to behave more like they do in the fish. But it requires injuring the tissue.

“From a practical standpoint, if you’re trying to regenerate the retina to restore a person’s vision, it is counterproductive to injure it first to activate the Müller glia,” said Bo Chen, Ph.D., associate professor of ophthalmology and director of the Ocular Stem Cell Program at the Icahn School of Medicine at Mount Sinai, New York.

“We wanted to see if we could program Müller glia to become rod photoreceptors in a living mouse without having to injure its retina,” said Chen, the study’s lead investigator.

In the first phase of a two-stage reprogramming process Chen’s team spurred Müller glia in normal mice to divide by injecting their eyes with a gene to turn on a protein called beta-catenin. Weeks later, they injected the mice’s eyes with factors that encouraged the newly divided cells to develop into rod photoreceptors.

The researchers used microscopy to visually track the newly formed cells. They found that the newly formed rod photoreceptors looked structurally no different from real photoreceptors. In addition, synaptic structures that allow the rods to communicate with other types of neurons within the retina had also formed. To determine whether the Müller glia-derived rod photoreceptors were functional, they tested the treatment in mice with congenital blindness, which meant that they were born without functional rod photoreceptors.

In the treated mice that were born blind, Müller glia-derived rods developed just as effectively as they had in normal mice. Functionally, they confirmed that the newly formed rods were communicating with other types of retinal neurons across synapses. Furthermore, light responses recorded from retinal ganglion cells—neurons that carry signals from photoreceptors to the brain—and measurements of brain activity confirmed that the newly-formed rods were in fact integrating in the visual pathway circuitry, from the retina to the primary visual cortex in the brain.

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Two Special Needs Dogs Get a Lift to a Loving Home

Among the victims of severe weather that battered western Kentucky last February was a pair of two-year-old German Shepherd-mixes. Stranded on a hill and marooned by rising floodwaters, the dogs were rescued by Good Samaritans who drove them to a local shelter.

“They were very scared, and trembling and whining,” recalls Kathy Baird, Animal Service Coordinator at the Union County Animal Shelter in Morganfield, Kentucky. “Neither knew how to walk on a leash; we had to carry them in and out for over a week before we could transition to leash walks.” 


Left: Badger (formerly Bert) with Bear (formerly Ernie). Right: Badger. 

Shelter staff knew that finding a home together for two large, bonded dogs—whom Kathy named Ernie and Bert­—would be challenging. On top of that, they discovered Ernie was blind and Bert had limited vision. Both also tested positive for heartworm disease. 

“I began to get discouraged at their future prospects,” admits Kathy. “But spending just 10 minutes with them always renewed my hope. I think they knew we wanted to help them.” 

“They quickly began to trust staff and follow our voices,” says Kathy. “They loved attention and each other, and even with all their challenges, seemed to love life.”

Kathy set about finding a partner shelter willing to take two dogs with medical and physical concerns. At the annual Kentucky Animal Care & Control Conference in Louisville in mid-March, she spread the word about the pair, and soon received a call from the Kentucky Humane Society, an ASPCA Relocation partner which specializes in hard to place animals with disabilities. Soon after, KHS earmarked Ernie and Bert for transport to the Humane Society of West Michigan (HSWM) in Grand Rapids.

The ASPCA WaterShed Animal Fund Relocation team also jumped into action to tackle logistics for the dogs’ transport. The team verified that both dogs met the Association of Shelter Veterinarians’ transport guidelines for animals infected with heartworm, as well as the State of Michigan’s guidelines. A volunteer then drove the dogs to KHS where they boarded the transport vehicle to Michigan.

On March 28, exactly one month and a day after their rescue, Ernie and Bert arrived in Grand Rapids. HSWM staff soon realized that Ernie relied heavily on Bert to help guide him and give him confidence. Bert, playful and independent, would check on Ernie frequently. 

“We didn’t really view these dogs as challenging,” says Namiko Ota-Noveskey, Behavior Specialist at HSWM, which successfully places special needs animals. “Both were social with people and other dogs. They just needed some medical help and a home together. We made sure they had a good quality of life until we found a special someone who would feel a connection.”

That special someone turned out to be Eric S., a recreation therapist for dementia patients at a local hospital. Eric came across Bert and Ernie’s profiles while browsing HSWM’s website, and soon discovered the two were “a package deal.” He called his fiancé Tiffany, who told him to “go for it” and adopt the pair. Ernie and Bert would join the couple’s four-year-old Beagle-mix, Tod. 

“What’s one more?” asks Eric, who admits that his profession and experience working with people with cognitive and intellectual challenges influenced his decision to adopt the two special needs dogs. 


Left: Badger playing with Tod. Right: Tod enjoying some playtime in the snow. 

In their new home, Ernie and Bert are now called Bear (for his love of hiding and hibernating) and Badger (who seeks Bear out and won’t stop until he finds him). 

“We meet them where they are, on their terms, and not where we want them to be,” Eric explains.

Patience is always crucial in raising special needs pets. Little things, like making sure the dogs are not underfoot or blocking a busy doorway, must be taken into account. “Everything just takes more time,” says Eric. 

Though unable to associate visual cues with commands, Bear is inquisitive and eager to please. Badger, though stubborn, picks up on things quickly and knows “sit.” Both dogs are also learning house manners, which includes staying off of the couch unless invited. 

Eric and Tiffany followed through with Bear and Badger’s heartworm treatment, restricting their activity for several weeks, a challenge for the rambunctious duo. Both dogs are due to be retested in six months.

“It really took a village to achieve their success,” says Kathy, who explains that Union County animals are routinely transported to shelter partners in other states by volunteers. “Without our volunteers, these opportunities would be missed.”

“We may take two steps forward and one step back,” says Eric of the duo’s limitations, “But they will adapt—and we’ll help them reach their true potential.”

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12 Brand-Name Drugs That May Never Go Generic


A recent analysis by I-MAK reveals that drug makers have leveraged the patent system to prevent generic competition, retain monopolies on expensive drugs and raise drug prices. This research comes months after the Trump administration released the American Patients First blueprint for lowering drug prices. Among the many initiatives included in the blueprint, the administration discussed strategies for increasing access to affordable generic and biosimilar drugs.

Trump is set to make an announcement about drug prices later this week. While no specifics of the announcement are known, with the support of I-MAK’s research, it’s clear that preventing companies from over patenting drugs could be a good next step in curbing high drug costs.

How do manufacturers prevent generic competition?

When President Reagan signed the Drug Price Competition and Patent Term Restoration Act (also known as the Hatch-Waxman Amendments) in 1985, drug makers were given the leverage to place long-standing patents on their drugs—for essentially the first time ever. Originally, the Act was intended to spur new drug development, incentivizing manufacturers to create new medications and shoulder the expensive cost of research and development in exchange for up to 20 years of market exclusivity.

Drug makers have since found loopholes in the patent system and turned 20 years of price protection into nearly 50 years in some cases. How? By covering their drugs with hundreds of patents that have allowed them to prevent cheaper alternatives from being manufactured—and hike prices.

The top 12 grossing drugs of 2017 have an average of 71 issued patents and at least 31 more years of patent monopoly. Some—like Enbrel and Humira—can cost well over $5,000 for a one-month supply.

 

In some cases, the sheer number of patent applications that a manufacturer submits can be exorbitant. For example, Abbvie, the manufacturer of immunosuppressant drug Humira, applied for 247 patents for the drug, preventing a generic from entering the market for at least the next 39 years. Avastin and Rituxan, often used in cancer treatments, saw 219 and 204 patent applications, respectively.

In general, the more patents a drug has, the longer we will have to wait for a generic. Of the 12 drugs in the analysis, Humira is covered by the most patents, and cancer medication Herceptin is leading the board in terms of wait time for a generic to be released. Manufacturers of Herceptin, Roche and Genentech, have applied for 186 patents for the drug, resulting in 48 years of market exclusivity.

Manufacturer Pfizer tops the charts in terms of price increases since 2012, increasing the price of blockbuster drug Lyrica by 163% during that time. Lyrica’s patents, along with its unencumbered price hikes, has resulted in over $5 billion in global sales for Pfizer. Expect Lyrica to get even more expensive as Pfizer holds market exclusivity for another 32 years.

A note about biologics and biosimilars:

Keep in mind that some of the drugs on this list (like Humira, Lantus and Herceptin) are biologics, a class of drugs that include some of the most expensive medications in the world—here’s why this matters.

Biologic drugs are made out of living cells, which makes them notoriously difficult to replicate exactly, and are thus insulated from generic competition. In an effort to reduce the cost for these expensive biologics, the FDA has urged competitors to develop biosimilars, drugs that are similar to biologics already approved by the FDA. However, unlike a generic drug, biosimilars are not interchangeable with the original brand drugs, and are still quite expensive.

In other words, biologics on this list may never see a generic, and not because they are over-patented, but because they are near impossible to replicate.

So, what does this mean?

As you may have guessed, this probably doesn’t bode well for drug prices, and you’re right. In the past six years, the prices of four of these 12 drugs have more than doubled. What’s more, according to I-MAK, these 12 drugs cost health insurers, government payers and consumers a total of $96 billion in 2017 alone.

Manufacturers typically raise drug prices yearly, by as much as 10%. If manufacturers hold on to their monopolies for even the next 10 years, prices for these lifesaving drugs should continue to increase.

Is there anything being done to stop this?

Amid growing concern around drug spending, in May, President Trump called out manufacturers for exploiting the patent system, blaming them in part for the price of prescription drugs. In that same speech, Donald Trump indicated lowering drug prices was “one of [his] greatest priorities” and promised to release a plan to curb high drug prices. Unfortunately, no plan has been released yet.

Since that speech, the White House has called out specific manufacturers for their price hikes, but there has been little done to revamp the patent system. Stay tuned.

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Study: What patients really think about opioid vs non-opioid medications for chronic pain

Prescriptions of opioids for chronic pain has increased dramatically since the 1990s in spite of their known harms. Despite a shortage of scientific studies on the long-term effectiveness of opioids such as morphine, oxycodone and hydrocodone, they are frequently perceived to be stronger, more powerful pain relievers than non-opioid alternatives like acetaminophen or ibuprofen.

A new study investigates pre-existing perceptions about pain medications by individuals with chronic pain and how these perceptions relate to patients’ experiences with these medications.

“‘I Was a Little Surprised’: Qualitative Insights from Patients Enrolled in a 12-Month Trial Comparing Opioids to Non-Opioid Medications for Chronic Musculoskeletal Pain” will be published in a future print issue of the Journal of Pain, the peer-reviewed journal of the American Pain Society.

The study provides insights into the results of “The Strategies for Prescribing Analgesics Comparative Effectiveness” (SPACE) trial, a landmark randomized controlled trial comparing benefits and harms of opioid versus non-opioid medications over 12 months for chronic musculoskeletal pain. SPACE, the results of which were published earlier this year in JAMA, found that opioid medications were not better at improving pain that interfered with walking, work or sleep over 12 months for individuals with chronic back pain or arthritic hips or knees compared to non-opioid medications. SPACE also found that adverse medication-related symptoms were more common in the patients who took opioids.

The Journal of Pain study explores patients’ experiences, including their perceptions of medications and experiences with the SPACE study itself. It found that, despite strongly held beliefs about opioid and non-opioid medications, patients were often surprised by their results.

The study also found that the patient-provider relationship, in this case a novel patient-pharmacist telecare collaborative management care model, may have an important influence on patient’s perceptions of and responses to pain medications.

“Given evidence suggesting that treatment expectations can influence treatment response, we sought to gain a more complete understanding of the potential role of expectations and perceptions of opioids held by patients with chronic back, hip and knee pain,” said Journal of Pain study corresponding author Marianne Matthias, a research scientist with the VA Center for Health Information and Communication at the Richard L. Roudebush VA Medical Center and with the Regenstrief Institute’s Center for Health Services Research.

“We found that personalized care by someone who cares—in this case by a pharmacist—often meant more to patients than the actual medications they were taking. Patients seem to value working with someone who cares about them and can help to meet their physical and emotional needs.”

In the Journal of Pain study, Dr. Matthias and colleagues interviewed 34 SPACE participants, all of whom were patients at a VA hospital. One patient who was treated in SPACE’s opioid arm and transitioned to non-opioid medications after study completion described his experience with both treatment approaches, including his surprise that the non-opioid medications seemed to be as effective as the opioid he had been taking.

Patient: “Well, the hydrocodone was probably most effective because it was more powerful of any that I’ve taken. And, you know, it does more than just relieve the pain on my knee, it relieves anxiety and, you know, a few other things.”

Interviewer: And, now, when you switched over from the hydrocodone to the acetaminophen and lidocaine, were the results any different than what you expected?

Patient: “No, the results were about what I expected. The extra heat on my knee that provided some relief and the acetaminophen…between the two of them, it did the same about as the hydrocodone. I was a little surprised.”

Another individual, who received non-opioids said:

Patient: “I can pick my kid up, throw him around, spin him around, whatever, and I feel great…. I even feel like getting teary because I’m just so happy. I am. I’m able to do a lot of things that I couldn’t. A lot more things than I thought I would be able to even [do]…. I’m also a lot more muscular than I was a year and a half ago, too.”

He went on to describe how his results surprised him.

“I was expecting it not to be 180-degree turn because I went from being just miserable every day to being just, for the most part, happy. I can basically just bounce right out of bed.”

In addition, this patient described a change in his beliefs about opioid and non-opioid medications.

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