Pfizer (PFE) is scheduled to report the results of its fourth fiscal quarter before the market open on January 29, with a conference call scheduled for 10:00 am EDT. What to watch for: 1. GUIDANCE: Along with its third quarter financial report in late October, the drug giant gave its view for FY18. Pfizer narrowed its FY18 adjusted EPS view to $2.98-$3.02 from $2.95-$3.05 on a narrowed revenue view of $53B-$53.7B from its previous view of $53B-$55B. At the time consensus was $2.99 and $54.15B, respectively. Pfizer said Innovative Health revenues first half revenues increased 5% operationally, primarily driven by continued growth from key brands including Eliquis globally. Gains in those product sales were partially offset primarily by the loss of exclusivity of Viagra in the U.S. and lower revenues for Enbrel in most developed Europe markets primarily due to continued biosimilar competition. Essential Health revenues declined 4% operationally, negatively impacted primarily by a 14% operational decline in the legacy established products portfolio in developed markets, primarily driven by industry-wide pricing challenges in the U.S. and generic competition. 2. INCREASING DRUG PRICES: On November 16, Pfizer shared its plans to maintain the current list prices for about 90% of its medicines, and effective January 15, to increase the list price of 10% of its entire drug portfolio — 41 medicines only. These list price increases are expected to be offset by higher rebates and discounts paid to insurance companies and pharmacy benefit managers and the net effect on revenue growth in the U.S. in 2019 is expected to be zero. Given the higher rebates and discounts, the company expects the healthcare system will share those benefits with patients so they do not experience higher costs for their medicines. Soon after news of the price increases was out, Wells Fargo analyst David Maris told investors that Pfizer earlier this year was criticized by the Trump administration for drug price increases, and as a result, it rolled the price increases back. However, Pfizer’s new price increases “are not egregious” and its advance warning may be an attempt to see if minor price increases will also bring the administration’s rebuke, said Maris. 3. PIPELINE: In mid-December, Pfizer announced the initiation of a Phase 3 program for its 20-Valent pneumococcal conjugate vaccine candidate, PF-06482077, for the prevention of invasive disease and pneumonia caused by Streptococcus pneumonia. Additionally, Pfizer announced that the Committee for Medicinal Products for Human Use of the European Medicines Agency has adopted a positive opinion, recommending marketing authorization for Zirabev, a potential biosimilar to Avastin. Zibarevis a monoclonal antibody for the treatment of metastatic carcinoma of the colon or rectum, metastatic breast cancer, unresectable advanced, metastatic or recurrent non-small cell lung cancer, advanced and/or metastatic renal cell cancer and persistent, recurrent or metastatic carcinoma of the cervix. 4. PFIZER, GSK TEAM ON CONSUMER HEALTHCARE: Pfizer and GlaxoSmithKline (GSK) announced on December 19, that they have entered into an agreement to create a consumer healthcare company. The boards of both companies have unanimously approved the transaction under which Pfizer will contribute its consumer healthcare business to GlaxoSmithKline’s existing consumer healthcare business.
Monday, January 28, 2019
Zai Lab nabs speedy China regulatory review for PARP drug Zejula
Chinese regulatory officials are signaling that they’re ready to whisk Zejula through the regulatory process.
Zai Lab $ZLAB said this morning that the Center for Drug Evaluation of China’s National Medical Products Administration has offered a priority review for this drug, the PARP therapy niraparib in-licensed from Tesaro. They’re looking for an OK in China to market the drug for ovarian cancer.
Zai Lab nabbed a fast OK for Zejula in Hong Kong at the end of 2018, allowing them to begin rolling it out in the huge Asian nation.
Chinese officials have been ramping up speedy drug approvals, looking to advantage companies like Zai Lab, homegrown outfits that have been snapping up late-stage and commercial products looking to build quick commercial portfolios. Priority reviews and the promise of swift action after lowering the bar on data requirements have shaken up the Asian market.
Once the $5 billion Tesaro buyout goes through at GSK, Zai Lab will be partnered with the pharma giant, which has large operations inside China and has had for years.
Adverse Birth Outcomes Up With Medically Assisted Reproduction
Children born by medically assisted reproduction have an increased risk for adverse birth outcomes; however, the increased risk appears to be attributable to other factors, according to a study published online Jan. 14 in The Lancet.
Alice Goisis, Ph.D., from the London School of Economics and Political Science, and colleagues used data from Finnish administrative registers and examined birth weight, gestational age, risk for low birth weight, and risk for preterm birth for children conceived by medically assisted reproduction and children conceived naturally.
Four percent of children (2,776 children) in the sample were conceived by medically assisted reproduction between 1995 and 2000; 1,245 children were included in a sibling comparison. The researchers found that outcomes were worse for children conceived by medically assisted reproduction compared with those conceived naturally for all outcomes, even after adjustment for observed child and parent characteristics (e.g., −60 g difference in birth weight [95 percent confidence interval, −86 to −34 g]; 2.15 percentage point increased risk for preterm delivery [95 percent confidence interval, 1.07 to 3.24]). The gap in birth outcomes was attenuated in the sibling comparison (e.g., −31 g difference in birth weight [95 percent confidence interval, −85 to 22 g] and 1.56 percentage point increased risk for preterm delivery [95 percent confidence interval, −1.26 to 4.38]).
“These findings support the argument that medically assisted reproduction treatments per se have little or no effect on the risk of adverse birth outcomes,” the authors write.
Diabetes lands the most seniors at ER
For seniors who often find themselves in the ER, complications from diabetes is the most common culprit, new research shows.
Not only that, these chronically ill patients remain in the hospital longer and require more treatment and resources, noted the authors of the study. It was published in the Jan. 28 issue of the Annals of Internal Medicine.
“Efforts to improve care for vulnerable older Americans should focus on enhancing delivery and decreasing utilization,” said lead author Dr. Edward Castillo. He’s an associate adjunct professor in the department of emergency medicine at the University of California, San Diego.
“Older patients are more likely to have multiple chronic conditions, which makes emergency care increasingly complex. A better understanding of older patients opens the door for interventions in and beyond the emergency department [ED],” Castillo explained in a journal news release.
The researchers examined 2014 data on California seniors defined as frequent users, meaning they visited an ED six times or more that year.
The most common conditions that took them to an emergency room were diabetes (26 percent), chronic pulmonary disease (21.5 percent), kidney disease (19 percent), congestive heart failure (16 percent), and peripheral vascular disease, or PAD (15 percent), which is blockage or damage to veins or arteries.
Compared to less frequent ED users, frequent users were more likely to have been admitted/transferred (86 percent vs. 44.6 percent) and to discontinue care (8 percent vs. 2 percent).
Frequent users were more likely to have more than one health problem, and 20 percent of them visited three or more hospitals during the study year.
“This study shows that there are opportunities for cost savings and more targeted preventive efforts across the care continuum for older patients,” said study co-author Kelly Ko. He is director of clinical research at West Health, a nonprofit medical research organization.
“We can do more to help seniors stay healthier and potentially limit the number of times they have to visit the emergency department,” Ko said.
In 2012, seniors accounted for 15 percent of the U.S. population but 21 percent of total health spending and almost half of the top 1 percent of spending, according to the Agency for Healthcare Research and Quality.
More than 15 percent of U.S. emergency department visits are made by patients 65 and older, according to the U.S. Centers for Disease Control and Prevention.
More information
The American College of Emergency Physicians offers tips for taking seniors to the emergency department.
SOURCE: Annals of Internal Medicine, news release, Jan. 28, 2019
Acceleron, Genomic Health among week’s notable insider transactions
Celgene purchased 706,206 shares OF Acceleron Pharma, Baker Bros. sold 208,831 shares of Genomic Health
NOTABLE INSIDER PURCHASES: Significant Insider purchases reported in the prior week from January 21 through January 25 include:
- Beneficial Owner of Acceleron Pharma (XLRN) Celgene (CELG) purchased 706,206 shares of company stock at $43 per share for a total transaction value of $30,366,858
- Director and Beneficial Owner of Bellerophon Therapeutics (BLPH) Theodore Wang Purchased 450,000 shares of company stock at an average price of 70c per share for a total transaction value of $315,000
NOTABLE INSIDER SALES: Significant Insider sales reported in the prior week from January 21 through January 25 include:
- Shareholder of Genomic Health (GHDX) Baker Bros. sold 208,831 shares of company stock at $71.86 for a total transaction value of $15,006,345
- Shareholder of MedEquities Realty Trust (MRT) BlueMountain Capital sold 362,699 of company stock at $10.94 per share for a total transaction value of $3,969,197
Stress and dream sleep are linked to pathways of brain cell death and survival
The first and most distinct consequence of daily mild stress is an increase in rapid-eye-movement (REM) sleep, a new study in the journal PNAS reports. The research also demonstrated that this increase is associated with genes involved in cell death and survival.
REM sleep, also known as paradoxical sleep, is the sleep state during which we have most of our dreams and is involved in the regulation of emotions and memory consolidation. REM sleep disturbances are common in mood disorders, such as depression. However, little was known about how sleep changes are linked to molecular changes in the brain.
During this 9-week study, conducted by researchers from the Surrey Sleep Research Centre at the University of Surrey in collaboration with Eli Lilly, mice were intermittently exposed to a variety of mild stressors, such as the odour of a predator. Mice exposed to mild stressors developed signs of depression; they were less engaged in self-care activities; were less likely to participate in pleasurable activities such as eating appetising food, and became less social and interested in mice they hadn’t encountered before.
Monitoring their sleeping patterns, researchers identified an increase in the duration and continuity of REM sleep and specific brain oscillations characteristic of REM sleep, whereas ‘deep’ sleep, or non-REM sleep, did not change. The changes in REM sleep were very tightly linked to deficiency in the regulation of the stress hormone corticosterone. Mild stress also caused changes in gene expression in the brain.
To further understand the link between stress, the stress hormone, REM sleep and gene expression, researchers undertook a novel machine-learning approach, which identifies groups of genes that can predict the observed sleep, behavioural and hormonal characteristics. This revealed that REM sleep, the regulation of the stress hormone and a behavioural sign of depression were closely associated with molecular pathways involved in the death and survival of cells in the brain, primarily in the hippocampus.
These data suggest that an increase in REM sleep can activate signalling pathways in the brain which allow it to change in response to ‘mildly stressful’ waking experiences. The findings may provide a better understanding of how stress leads to mood disorders and how changes in sleep may contribute to this.
First author Dr. Mathieu Nollet said: “The comprehensive analysis of the behavioural changes in combination with the sleep and gene expression analyses make a strong case for the important role of REM sleep in the brain response to stress.”
Senior Author Dr. Raphaelle Winsky-Sommerer, Reader in Sleep & Circadian Rhythms at the University of Surrey, said: “The behavioural and sleep changes are very similar to those observed in depression and we therefore believe that the molecular changes observed in mice may also be relevant to the response to stress and mood disorders in humans.”
Professor Derk-Jan Dijk, who leads the Surrey Sleep Research Centre at the University of Surrey, said: “Once again we see that sleep is a very sensitive and early marker of the brain response to the challenges faced during wakefulness. It now will be important to see how sleep is involved in the recovery from stress.”
Explore further
More information: Mathieu Nollet et al. REM sleep’s unique associations with corticosterone regulation, apoptotic pathways, and behavior in chronic stress in mice, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073/pnas.1816456116
Does intensive blood pressure control reduce dementia?
Intensive lowering of blood pressure did not significantly reduce dementia risk but did have a measurable impact on mild cognitive impairment (MCI), according to the final, peer-reviewed results from the Systolic Blood Pressure Intervention Trial (SPRINT) Memory and Cognition in Decreased Hypertension (SPRINT MIND). SPRINT MIND secondary results are the first to show an intervention that significantly reduces the occurrence of MCI, which is a well-established precursor of dementia. The results were reported Jan. 28, 2019 in the Journal of the American Medical Association. SPRINT MIND was an integral aspect of the initial design for SPRINT, a large, randomized clinical trial of intensive blood pressure lowering on cardiovascular and renal disease; both were funded by the National Institutes of Health.
“Dementia continues to be a large public health challenge, and based on the primary results of this study, we still have yet to find an intervention strategy proven to reduce the risk of dementia,” said Richard J. Hodes, M.D., director of the National Institute on Aging (NIA), part of NIH and the lead institute on Alzheimer’s research. “Nevertheless, the secondary results showing that intensive lowering of blood pressure may reduce risk for MCI, a known risk factor for dementia, gives us additional avenues to explore on the path to prevention.”
MCI is a condition in which people have more difficulty with cognition, thinking, remembering, and reasoning, than normal for people their age. Dementia is a more severe form of loss in cognitive functions that interferes with daily life. Alzheimer’s disease is the most common type of dementia. High blood pressure, or hypertension, is very common in persons over the age of 50 and a leading risk factor for heart disease, stroke, kidney failure, and a growing body of research suggests that it may increase risk for dementia later in life.
The participants in SPRINT were adults 50 years and older at high risk for cardiovascular disease. Results of the SPRINT trial, which ended early, showed that intensive blood pressure control, i.e., a systolic blood pressure target of less than 120 mmHg (<120 mmHg), compared to a standard target of less than 140 mmHg (<140 mmHg), reduced cardiovascular events and overall mortality. Between November 2010 and March 2013 more than 9,300 participants were randomized to the two target groups with nearly 4,700 in each group. In August 2015, the SPRINT trial was stopped after 3.3 years of treatment when the major beneficial effects of intensive blood pressure management on mortality and cardiovascular disease were discovered. Assessment for development of dementia and MCI continued for the full planned five years.
SPRINT MIND aimed to address whether intensive blood pressure control would also reduce the risk of developing dementia and cognitive impairment over the ensuing five years. Cognitive assessments were given to participants who had high blood pressure but no history of stroke or diabetes at the start of the trial, and over 91 percent had at least one follow up. Participants were classified into one of three categories: no cognitive impairment, MCI, or probable dementia.
The SPRINT MIND Research Group, including corresponding author Jeff D. Williamson, M.D., M.H.S., from Wake Forest School of Medicine, Winston-Salem, North Carolina, noted that the primary results of this analysis found no statistically significant difference between standard and intensive treatment in the proportion of participants that were diagnosed with dementia. The study, however, had fewer cases of dementia than expected. Nevertheless, the secondary results suggested that the intensive treatment reduced the risk of MCI and the combined risk of MCI and dementia. Due to the success of the SPRINT trial on the cardiovascular outcomes, the study intervention was stopped early; as a result, participants were treated for a shorter period than originally planned. The authors concluded that the shorter time and the unexpected fewer cases of dementia may have made it difficult to determine the role of intensive blood pressure control on dementia.
“The fact that there was still an MCI result when the study was cut short makes these results encouraging,” explained Laurie Ryan, Ph.D., chief of the Dementias of Aging Branch in the NIA Division of Neuroscience.
The authors emphasized that this is the first randomized clinical trial demonstrating that an intervention significantly reduces the occurrence of MCI, which is an established risk factor and often a precursor for dementia. An important conclusion from this research is that the intensive lowering of systolic blood pressure to <120 mmHg target—which reduces the risk of cardiovascular events and mortality—is safe for the brain.
“This is a landmark study in that it is the first trial of its size and scope to look at a modifiable risk factor for dementia and MCI,” said Lenore J. Launer, Ph.D., a senior investigator in the NIA Laboratory of Epidemiology and Population Sciences and co-author of the paper. “The study had a carefully designed hypothesis, used approved appropriate tools to assess dementia and MCI, was blinded for diagnosis, and got a good sample of older people.”
The authors noted that there currently are no proven interventions that prevent or delay the incidence of MCI or dementia. Therefore, people should consult with their healthcare providers to decide the best blood pressure goals for themselves and to determine how to reach those goals (for example, introducing lifestyle changes such as diet and exercise; or lifestyle changes with addition of blood pressure medications).
“This study is in line with where the field of dementia research is going: preventing memory loss earlier,” added Ryan, who is also the program lead for SPRINT MIND. “Much like we have research-based interventions for heart health and cancer prevention, we hope to have guidance based on this and subsequent studies that will more definitively show how to slow or even stop dementia well before symptoms appear.”
More information: Journal of the American Medical Association (2019). DOI: 10.1001/jama.2018.21442
Subscribe to:
Posts (Atom)