Canaccord analyst Michelle Gilson initiated Retrophin with a Buy rating citing what she views as an attractive valuation given the upside potential provided by the clinical stage pipeline. She sees limited downside risk but upside catalysts with POC data for CNSA-001 in early 2019 and Phase 3 FORT data in PKAN in the second half 2019. Gilson has a $36 price target on Retrophin shares.
Friday, August 17, 2018
Jazz Pharmaceuticals price target raised to $210 from $200 at Leerink
Leerink analyst Ami Fadia raised Jazz Pharmaceuticals for solriamfetol based on results from the firm’s MEDACorp physician survey on the Excessive Sleepiness market. Fadia continues to see solriamfetol as a key growth asset in the outer years when Xyrem faces competition. The analyst rates Jazz an Outperform and increased its price target to $210 from $200.
Start of Phase 3 trial for EB-101 an important catalyst for Abeona, says Citi
Following the premature publication of a draft protocol for Abeona Therapeutics’ EB-101 trial by the company’s collaborator, Citi analyst Liav Abraham said the start of this pivotal trial represents an important near-term catalyst for the stock. The analyst, who said that the Phase I/II trial for EB-101 in recessive dystrophic epidermolysis bullosa delivered “compelling data” on wound closure at 3 and 6-months, keeps a Buy rating on Abeona shares.
Thursday, August 16, 2018
Toward Opioid-Free Surgery
Charles N. Cornell, MD: My name is Dr Charles Cornell. I’m an orthopedic surgeon at the Hospital for Special Surgery. I specialize in total joint replacement of the hip and knee. I’m joined today by my friend and colleague, Dr Seth Waldman, who is the director of our chronic pain service at the Hospital for Special Surgery.
Our purpose today is to have a conversation about a recent forum that was held at the hospital called “Toward Opioid-Free Arthroplasty.” In the 1990s, we were encouraged to be aggressive in managing postoperative pain, especially for our [orthopedic] patients. The general perception was that we were inadequately managing postoperative pain. As a result, we began relying heavily on opioids to manage postoperative pain.
In the early 2000s, the concept of multimodal analgesia and multimodal anesthesia came to the forefront. We learned to reduce our dependency on opioids by utilizing other medications such as nonsteroidal anti-inflammatory drugs, neuroleptic agents, and acetaminophen.
We also increased our dependence on postoperative epidural analgesia. We moved our nerve blocks to the periphery so that they are sensory-only blocks that don’t interfere with motor function and we are able to mobilize our patients sooner. Today, we ambulate our patients within a few hours of surgery. These new techniques have allowed us to manage pain quite effectively and decrease our dependence on opioids.
Around 2015 to 2016, I became aware of the need to change my own personal practice, so I sought the help of Dr Waldman. We learned that many of my colleagues at the hospital were experiencing the same problem, so Dr Waldman put together an educational program on opioid prescribing, problems with prescribing, and opioid pharmacology, and extended it to all members of our staff.
What came out of it was a realization that we needed to change, and we’ve dramatically improved our opioid prescribing practices at the hospital. The basis for that has been multimodal analgesia, changes to our approach to physical therapy so that the physical therapy doesn’t contribute to postoperative pain, and addressing patient expectations and reassuring patients that we can manage their pain without opioid medications, making recovery from surgery much safer, with fewer complications.
Let me introduce Dr Seth Waldman, the director of our chronic pain service.
Standardizing Prescribing Practices
Seth A. Waldman, MD: Thank you very much. When this process started, we were in a position similar to that of many others throughout the country who recognized that a high volume of people coming in for routine surgery were on narcotic pain medication. These patients were sometimes not properly evaluated before they came in, which placed them at increased risk not only at the time of surgery but also after the surgery. Patients need to be properly assessed for risk with respect to other narcotics and the presence of factors such as alcohol use. There is also the question of hyperalgesia, which is the increased level of pain that people might have after exposure to opioid pain medications.
We started a series of steps here at the hospital. First, we analyzed prescribing practices throughout the hospital by looking at volumes of prescriptions being written to establish service-specific guidelines. In other words, we wanted to make sure that most people having an ACL repair would get about the same amount of medicine and most people having a knee replacement would get about the same amount of medicine—guidelines for our medical staff, physician assistants, and nurse practitioners so that we’re all on the same page.
Next, we changed documentation and standardized it to make sure that everyone was prescribing in a similar way and documenting in a similar way to justify the reasons for writing the prescription. The most important part of this was the development of a preoperative evaluation service. In the early phases, we relied on the surgeon or the preoperative clearance physician in the medical department to [assess] the risk, but then we formalized that process. Now, at every step along the way—from when a patient first presents to a surgeon as a possible candidate for a surgical procedure—the patient would be asked a series of questions: Are you on any medicine? Why are you on them? Who prescribes them? Do you have a history of substance abuse or alcohol use? Et cetera.
Every patient would be asked this series of questions. Anyone who meets any of these criteria is flagged to have an additional evaluation by the pain management physician. The pain management physician would speak with their prescriber, speak with the patient, and when necessary, get a toxicology screen. If there are risk factors or if there is a history [of abuse], the patient would be seen by our substance abuse counselor.
The purpose of all this is to make sure that patients are in optimal condition for surgery. If they had been on very high doses of medicine or if we find an addiction or alcohol issue, then we would address those issues with proper treatment before clearing them for elective surgery. Obviously, this does not get in the way of emergency procedures.
When we get those patients back, they are in a much better place to receive treatment, rehabilitate after surgery, and wean off opioid pain medications. A major driver of the opioid epidemic is the fact that people would sometimes have surgery, be started on medicine, and then remain on those medicines simply because they had become tolerant of the drug.
Putting this system in place has enabled us to gain a lot of headway in getting better outcomes and taking better care of our patients. One of the things that came out the opioid forum was to look at different ways in which we can focus our treatment to minimize the amount of narcotics used while patients are in the hospital. We decided to choose one of the more painful procedures and concentrated on knee arthroplasty because it’s a notoriously uncomfortable surgery that often requires opioids.
Present at the meeting were surgeons, anesthesiologists, bioethicists, and data analytics specialists to try to figure out ways in which we could identify patients who would be more likely to do well with this type of minimal or no opioid technique. How can we select patients, craft an anesthetic, and craft a postoperative plan such that exposure to opioids is minimized or eliminated? How can we best do that in a fair way so that we are not denying people good treatment but treating people to the best of our ability while minimizing their exposure to opioids?
Multimodal Pain Management
Cornell: One of the more interesting aspects of the meeting was input that we received from our guests from Europe, where very little opioid prescribing takes place. Our guest from Madrid was Dr Carlos Rodriguez Merchan, chief of the knee service at La Paz University Hospital in Madrid. He summarized his experience from the past 10 years, during which minimal narcotics were used in their patient population.
Their approach is quite different from ours, but it made us aware that we should be able to move towards less opioid prescribing for these painful procedures. The secret seems to be the use of multimodal approaches for pain management.
Waldman: I have to say that a substantial difference has been made in our acute pain service. Even 5 years ago—and certainly 10 or 20 years ago—we were able to use fewer narcotic medicines because of the use of prolonged regional anesthetics.
Our house anesthetic for knee replacement was usually a combined spinal epidural with epidural patient-controlled analgesia. Those patients are now having adductor canal blocks. Sometimes they’re having other peripheral nerve blocks and intravenous acetaminophen. That hasn’t affected our ability to mobilize them, and it allows us to get to the point of rehabilitation without having to initiate a high-dose opioid, minimizing our need to send patients home with opioids.
Cornell: That’s true. That has been my experience, moving away from dependence on the epidural anesthetic and epidural patient-controlled analgesia, which kept the patient down, toward the peripheral sensory nerve blocks that have no motor component. They effectively control early postoperative pain so that the patient is up and moving, functioning well.
In my experience, if they don’t have much pain in the early postoperative hours, they don’t have as much pain as patients used to during the abrupt transition from anesthesia to no anesthesia. Also, with help from you and the chronic pain service, we’ve standardized prescribing so that now we all know the recommended number of pills to prescribe and the recommended dosages. It is now common knowledge to everyone, and as a result, our prescriptions have gotten much smaller and our patients’ duration on opioids after total knee replacement, for instance, has been shorter. We used to expect our patients to take opioids for 4-6 weeks, but that has now been reduced to 7-10 days.
Waldman: What has been your experience with changes in patient expectations and the change in our culture [in regard to regional anesthesia]? It works well here because we use it, we expect it to work, and it’s part of the way we do things. Patients now come to the hospital expecting that they’re going to try to avoid using opioids, whereas 10 years ago, they expected opioids to be a large part of what they would need to drive the pain down. It seems as though there has been a cultural shift in the attitudes of the staff and the patients. They’re willing to put up with a little pain because they have a better respect for the potential risks of being exposed to opioids.
Cornell: You’re absolutely right. Patients commonly express their awareness of the opioid crisis, and their wish is to be off opioids as quickly as possible. They’re still concerned and there is still fear of postoperative pain, but our program has dealt with that in a very direct way. We are able to reassure our patients that their pain is going to be well managed, and that as a result of this program, we’re prescribing less opioids and using alternative medications with very beneficial effects.
For instance, we used to discharge our patients after total knee replacement with 120 pills. That has now been cut down to 60 pills. Very few of my patients are calling for an additional refill. The use of nonsteroidal anti-inflammatory drugs, the liberal use of acetaminophen, and use of cryotherapy modalities, cold therapy modalities, and modified physical therapy during the early postoperative period have all been big steps that helped us move forward in this area.
Waldman: Yes, absolutely. It has been a very gratifying change.
Our Goal: Take Good Care of People
Cornell: One of the things that came out of the forum was our consensus statement. The first element of our consensus statement is that whenever you prescribe a narcotic, you have to have a weaning process in mind. I thought that was a great point. Can you expand on that a little bit?
Waldman: As pain specialists, we’ve always looked at opioid prescribing as the initiation of a therapy. It’s not as dramatic as having a surgical procedure, but when you initiate opioid therapy, you’re assuming certain risks—not only the acute risks of nausea, itching, and constipation, but also the risk of oversedation, hyperalgesia, and addiction.
The goal is to take good care of people, allowing them to have a safe surgery and the quickest possible rehabilitation so they can get back to where they started, which is without pain and with good function. Inherent in that is the plan for weaning. I view opioids as a bridge to that. There are occasions when people need to be on chronic medicines, but there are many more occasions with acute injuries, particularly after surgery, when treatment with narcotics is part of the transition. We must use opioids at times, but we minimize their use because we expect certain risks. We’re bound to try to mitigate those risks when we prescribe them. Open-ended opioid prescribing is a thing of the past, except in very narrow circumstances.
Cornell: Did you want to make any other points or bring out some of the concluding remarks of the forum? Obviously, we want multimodal analgesia. That has been so successful for us and is high on our list on the consensus statement. Use multimodal approaches. An institution-wide, uniform approach has also been very helpful.
Waldman: An important part of the consensus statement, which was brought in by Travis Rieder, the bioethicist, is that our goal is to take good care of people. In our case, we’re taking good care of people who have had surgical procedures, and we should use whatever methods are necessary while always weighing the risks and benefits of what we are doing. We use an opioid when necessary, but if we have something safer and just as effective or safer and even more effective, we’re obliged to use it.
When we employ an opioid medicine that has some risks, it is incumbent on us to make sure we manage and monitor our patients properly so that nothing happens to them while they are under our care for that medication and that we return them to their former state as quickly as possible while minimizing risks. The best way to look at this is that the goal of our session, “Toward Opioid-Free Arthroplasty,” was to minimize exposure, minimize risk, and take good care of people. A byproduct of that is that we will use fewer or no opioids in some surgical patients.
Cornell: We’re receiving a large number of manuscripts from the participants. The topic is huge. Many of the papers address very specific protocols. Some of the papers are more general. When the forum is published, it’s going to have great appeal to a wide variety of readers. It will be very helpful to orthopedic surgeons, nurses, and all aspects of our field. This was a successful venture, and the end product is going to be valuable.
Waldman: Yes, absolutely. For me, this was a dream come true to be able to have this conversation, especially at this moment when both the medical and patient communities are receptive to this. What I saw in the hospital this week was almost unrecognizable compared with the way things were before. The expectations are more realistic, the outcomes are better, and the exposure to medicine is better and less risky. We are very much headed in the right direction.
Cornell: I feel very lucky to have worked with you on this. I’ve learned a lot from you. Thank you very much for not only participating in the forum but also helping me to produce this special issue of the HSS Journal, in which all the speakers and authors will be featured with their published articles. Thank you very much. You’re a true expert in this area and you’ve taught us all quite a lot.
Waldman: Thank you very much. I appreciate our collaboration on this. It was heartening to see the collaboration among all the specialties at our hospital [to address] the opioid crisis. I feel that the tide is turning in the direction of reducing exposure to opioids and improving medical and surgical care past the end of the opioid epidemic.
Is One Basal Insulin Just Like Another?
Hello. I’m Dr Charles Vega, and I am a clinical professor of family medicine at the University of California at Irvine. Welcome to Medscape Morning Report, our 1-minute news story for primary care.
A new review concludes that basal insulin analogs used in patients with type 2 diabetes do not differ substantially in their glucose-lowering effect.
Conclusive evidence about the comparative efficacy of the many available basal insulins has been lacking. This meta-analysis and systematic review, based on 39 trials involving 10 basal insulin analogs, was meant to fill that gap.
The results of this review come with several important caveats. First, the overall quality of the evidence included in this analysis was determined to be low.
Second, the researchers noted concerns about bias, which affected almost half of the studies that looked at changes in A1c and nearly all studies that assessed hypoglycemia.
In addition, conclusions about the comparative effects of newer-generation long-acting basal insulin analogs were based mostly on indirect rather than head-to-head comparisons.
This adds to the worrisome problem of poor evidence underpinning the care of patients with type 2 diabetes requiring insulin. Another recently published study[1] concluded that basal insulin analogs were no better than the old—and far less expensive—NPH insulin.
Bottom line: Many patients with diabetes will need insulin sooner or later. The higher cost of some newer insulins may not be matched by their clinical performance.
New Warning About Benzodiazepine Use and Dementia Risk
Yet another study has linked benzodiazepine use to an increased risk for Alzheimer’s disease (AD).
“Even though the association between benzodiazepine use and Alzheimer’s disease was small in this study, the threshold for prescribing these drugs should be high enough due to their overall adverse effect profile, including higher risk of falls and hip fractures,” lead author Vesa Tapiainen, MD, PhD, a student in the School of Pharmacy, University of Eastern Finland, Kuopio, told Medscape Medical News.
These drugs are often used to treat sleep problems, but their efficacy for this indication diminishes over time, whereas the risks for adverse events remain, she added.
“Physicians should consider the risks and benefits, as well as appropriate duration of treatment, before prescribing these drugs,” said Tapiainen.
Although other studies have linked benzodiazepines with AD risk, Tapiainen believes this one is the largest to date.
The study was published in the August issue of Acta Psychiatrica Scandinavica.
Widely Used
In addition to insomnia, benzodiazepines and other so-called “Z” drugs, such as zolpidem (multiple brands) and zopiclone (Lunesta, Sunovion), are used to treat other neuropsychiatric symptoms of dementia, such as anxiety.
Although these drugs have different molecular structures, they have a similar mechanism of action and similar anxiolytic, anticonvulsive, hypnotic, and relaxing effects. In addition, they have similar adverse effects, including drowsiness, and their use is associated with mobility problems, falls, and fractures.
Benzodiazepines are used in 9% to 32% of older patients, the authors report.
The researchers used the Medication Use and Alzheimer’s Disease (MEDALZ) cohort, which includes all 70,719 residents of Finland. The patients selected for the study had been diagnosed with AD between 2005 and 2011. The patients’ ages ranged from 34 to 105 years. The study also included 282,862 matched control persons from nation-wide registers.
AD diagnoses were based on criteria from the DSM‐IV, as well as from the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association, now known as the Alzheimer’s Association.
Investigators extracted information on drug use from the Finnish Prescription Register. They looked at short-, medium- and long-acting benzodiazepines and related drugs.
In addition, the researchers examined different durations of drug use (1 day to 1 month; 1 month to 1 year; 1 to 5 years; and more than 5 years), and cumulative consumption in defined daily doses (DDDs), divided by tertiles.
“Worrying” Results
To account for reverse causality, the researchers investigated drug use only from 1995 to 5 years before AD diagnosis.
They controlled for various chronic disorders, including asthma/chronic obstructive pulmonary disease, cardiovascular disease, and diabetes, as well as for substance abuse, socioeconomic status (SES), and use of antidepressants and antipsychotics. All confounders were extracted until 5 years before the AD diagnosis.
Results showed that compared to individuals who had not used any of the relevant drugs, any use was associated with an increased risk of AD (odds ratio [OR], 1.19, 95% confidence interval [CI], 1.17 – 1.21).
After adjusting for comorbidities, SES, and use of other psychotropic medications, the association was somewhat lower (OR, 1.06; 95% CI, 1.04 – 1.08).
Using statistical calculations, the authors determined that the proportion of AD cases that could be attributed to exposure to these drugs was 5.7%.
Although the authors acknowledge that the increased absolute risk is modest, they point out that because these drugs are frequently used in older people, even a small increase in risk may be important.
“This is worrying,” the investigators note, not only because these drugs are commonly used by older patients but also because, despite recommendations, they’re often used long term in this population of patients.
In this study, the AD risk with all drugs was highest in patients who used the drugs for longer than a year. In the fully adjusted model, there were no risks for use during periods of less than a month.
The risks and benefits of these drugs should be reevaluated regularly, stressed Tapiainen.
She added that targeting the causes of sleep problems in patients and using nonpharmacologic treatments “should be prioritized.”
The relationships uncovered by the authors were similar for the various drugs and for short-, medium- and long-acting formulations.
Puzzling Finding
Interestingly, lower average doses (<0.5 DDD/day) of many of the drugs increased the AD risk more than higher doses in the unadjusted model.
“We were puzzled by this observation and investigated it in more detail,” said Tapiainen. “This investigation revealed that those who used the highest average doses actually used these drugs for a shorter period of time, and so their total consumption was less.”
In addition, high and low doses may have been used for different indications.
The authors noted that the dose-response relationship that was uncovered for both cumulative consumption and duration was lessened in the highest drug dose category after adjusting for use of other psychotropics.
“This indicates that the association may be partially due to antidepressants and/or antipsychotics, or concomitant use of these medications,” said Tapiainen.
When asked whether the relationship between drug use and AD risk was more pronounced among the oldest patients in the study, Tapiainen said she and her colleagues did not investigate this in the published study.
“But because we found this question interesting, we did further analysis and found that the association was similar regardless of age,” she said.
A limitation of the study was that it did not include data regarding nonreimbursed drugs or drugs used in hospital.
Plausible Risk
Commenting on the findings for Medscape Medical News, David S. Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, and a member of the Alzheimer’s Association Medical and Scientific Advisory Council, noted that many studies have suggested that patients who are exposed to certain psychoactive drugs, such as those with cholinomimetic properties, are at increased risk for dementia.
“I therefore find it plausible that benzodiazepines and related drugs could carry the same risks,” he said.
However, he added that the risk uncovered in this current study was “very modest.”
When the authors refer to “risk of Alzheimer’s” they mean “risk of dementia,” said Knopman. “They have no evidence from either neuropathology or biomarkers that the affected individuals had amyloidosis and tauopathy — so Alzheimer’s disease in the biological sense of the word.”
Tapiainen noted that all AD cases in the study were clinically verified with CT/MRI and that the diagnoses were confirmed by a registered neurologist or geriatrician.
The “bottom line” for Knopman is the same — that use of certain psychoactive drugs seems to increase the risk for dementia.
However, it is unclear whether the drugs are temporarily worsening cognition or symptoms are being treated with these drugs, said Knopman.
“In other words, the direction of causality from drugs to dementia could go in either direction, and this study that used administrative data can’t determine the direction of causality,” he said.
Nevertheless, a take-home message is that benzodiazepines and related sleep medications should be avoided “if at all possible” in older individuals, said Knopman.
Also weighing in on the findings for Medscape Medical News, Ronald Petersen, MD, PhD, director, Alzheimer’s Disease Research Center, Mayo Clinic, agreed that it is “appropriate” to be cautious about benzodiazepine use.
Petersen said he found the study “interesting,” although he “would want to be certain the clinical diagnoses were not confounded by benzodiazepine use prior to testing.”
Dr Tapiainen, Dr Knopman, and Dr Petersen have disclosed no relevant financial relationships.
Acta Psychiatr Scand. 2018;138: 91-100. Abstract
As Millennials Pivot From Booze To Buds, Beer Industry Strikes Cannabis Links
The news of Constellation Brands, Inc. STZ 2.78%, producer of beers such as Corona and Modelo, increasing its stake in Canadian cannabis company Canopy Growth Corp CGC 3.71% with a $4 billion investment is only the latest link between companies in the business of a buzz.
The interest in cannabis-infused beverages comes as beer sales are falling:
Molson Coors Brewing Co TAP 1.07%‘s recent quarterly results revealed a marginal decline in second-quarter sales, hurt by lower volume and the adoption of new revenue recognition accounting standard.
Anheuser Busch Inbev NV (ADR) BUD 0.02% recently said its second-quarter U.S. revenues declined 3.1 percent, as its flagship Budweiser and Bud Light brands saw a 5-percent volume drop. The company is reportedly looking at other options such as low- or no-alcoholic beverages.
Trading Beer For Bud
Beer has fallen out of favor as consumers gravitate toward wine, which is seen as a healthier option; spirits; and weed.
The generation behind millennials, primarily the 21-25 age group, have put their weight behind cannabis rather than alcohol, according to Forbes.
Forbes highlighted research by the OutCo-Monocle Research Combine that suggested 51 percent of survey participants intended to swap alcohol for cannabis ahead of the legalization of recreational marijuana in California.
Source: Market Realist
Marriages Of Convenience
Molson Coors recently said its Canadian unit struck a joint venture with Hydropothecary Corp HYYDF 2.36% to explore opportunities to develop non-alcoholic, cannabis-infused beverages for the Canadian market.
Incidentally, Canada is close to legalizing recreational marijuana nationwide. Cannabis edibles and beverages, however, aren’t expected to be legalized until 2019.
“The new company will combine the proven beverage experience of Canada’s leading brewer with a recognized innovator in the fast-growing cannabis sector to explore the highly anticipated consumable cannabis market, which is expected to be legally permissible in Canada in 2019,” the companies said.
Also joining the bandwagon is Heineken N.V. (ADR) HEINY 0.89%, which through its Lagunitas unit, has launched Hi-Fi Hops, a cannabis-infused sparkling water. This is to be sold through a few dispensaries in California, where recreational marijuana is legal.
The company claims the product has zero alcohol, zero calories and zero carbs, and it comes in two versions: a 10-mg version with tetrahydrocannabinol and another with 5mg of THC and 5mg of cannabidiol, the non-psychoactive component of the cannabis plant.
A Promising Opportunity
For marijuana companies, the tie-up with big beer companies provides access to big capital. Retail investors have powered the marijuana industry up to this point, as institutional investors stay on the sidelines due to the uneven legislation across the country.
Cannabis-induced beverages are likely to disrupt the alcohol industry. States where recreational marijuana has been made legal have seen a 13-percent drop in binge drinking per month, theInlander said, quoting cannabis analyst Vivien Azer.
From a health care perspective, this is a welcome development given alcohol’s role in liver cirrhosis deaths.
Six out of 10 consumers of marijuana to prefer to consume it as an edible product, the Globe and Mail reported, citing Deloitte. And in the edible category, the accent is likely be on beverages.
Sales of cannabis-infused beverages will outstrip traditional soft drinks in convenience stores by 2030, according to Faircourt Asset Management CEO Charles Taerk’s projections, Bloomberg reported.
Subscribe to:
Posts (Atom)