Medtronic (MDT) today at its analyst meeting said it expects commercial launch of its surgical robot in fiscal 2020, which is roughly a year delay compared to the company’s prior expectations, Cantor Fitzgerald analyst Craig Bijou tells investors in a research note partially titled “ISRG’s Headstart Gets Bigger.” The analyst views the revised timing of the commercial launch of Medtronic’s robot as a “clear positive” for Intuitive Surgical (ISRG). With the commercial launches of the Medtronic and Johnson & Johnson (JNJ) robots at least 18 months away, Intuitive should continue to grow its global installed base, further advancing its global surgical robotics leadership position, Bijou writes. He reiterates his Overweight rating on the shares with a $510 price target. The stock in afternoon trading is up $8.46 to $486.39.
Tuesday, June 5, 2018
Allergan says board refreshment continues to be ‘top priority’
Allergan issued the following statement in response to a public shareholder letter: “Allergan’s board of directors and management welcome input from all our shareholders, and take into account their views. Our board and management are committed to creating a world class biopharmaceutical and aesthetics business and driving shareholder returns. The conclusion of our recently completed strategic review is to create a more focused Allergan that concentrates on four therapeutic areas where we have leadership positions and depth and breadth of our products and pipeline, and to pursue a disciplined capital allocation strategy to generate value for shareholders. Our board has been active and aggressive in board refreshment with three new directors joining our board over the past 16 months, and board refreshment continues to be a top priority. The board also strongly believes in independent leadership as exemplified by the role of Chris Coughlin, our lead independent director, who was chosen as Director of the Year by the National Association of Corporate Directors in 2015. Mr. Coughlin brings over 30 years of biopharmaceutical industry experience to the Allergan board. Our number one priority continues to be executing on operational excellence and delivering strong results to drive long term shareholder value.”
Merck said to be preparing for supply blackout amid Brexit
Merck is planning for the possibility of a temporary supply blackout when the U.K. leaves EU, and may stockpile as much as six months worth of goods, according to Bloomberg, citing a person familiar with the matter. The contingency plans include factoring in as much as two extra days of travel on routes between U.K. and EU destinations to allow for delays caused by document checks, source said.
Eisai, Biogen: Phase 2 Alzheimer’s med safe, well tolerated
Eisai (ESALY) and Biogen (BIIB) announced that elenbecestat was generally safe and well tolerated in a Phase II clinical study of the oral BACE inhibitor elenbecestat conducted in the United States, and the results demonstrated a statistically significant difference in amyloid beta levels in the brain measured by amyloid-PET. A numerical slowing of decline in functional clinical scales of a potentially clinically important difference was also observed, although this effect was not statistically significant. This study, a Phase II study of 70 patients, is the first study of a BACE inhibitor to show a statistically significant difference in amyloid beta in the brain while also suggesting a delay of clinical symptom decline in exploratory endpoints.Study 202 is a multicenter, randomized, double-blind, placebo- controlled parallel-group 18-month Phase II clinical study in patients with mild cognitive impairment due to Alzheimer’s disease, or mild to moderate dementia due to Alzheimer’s disease with confirmed amyloid pathology by PET screening. Seventy patients were randomized to four treatment arms receiving elenbecestat or placebo daily. During the study period, more than half the patients in the elenbecestat 5 mg and 15 mg arms were switched to the 50 mg arm for three months or more. The 50 mg treatment arm plus the group switched to the 50 mg arm are hereafter referred to as “50 mg total arm” with a mean duration of approximately 11 months on 50 mg per day. Elenbecestat demonstrated acceptable safety and tolerability profile through 18 months of study drug administration. In the elenbecestat 50 mg total arm, the six most common adverse events observed were contact dermatitis, upper respiratory infection, headache, diarrhea, fall, and dermatitis. No serious adverse reactions suggestive of hepatic toxicity were observed in this study. In addition to the safety objectives, the study assessed Abeta in the brain at 18 months as measured by amyloid PET as well as efficacy in terms of clinical symptoms, which were exploratory objectives in this study. The elenbecestat 50 mg total arm demonstrated a statistically significant difference in Abeta levels in the brain as measured by amyloid PET compared with placebo This is the first time in which a significant effect in Abeta in the brain using a BACE inhibitor was confirmed in a clinical study of patients with mild cognitive impairment through moderate Alzheimer’s dementia. CDR-SB was an exploratory endpoint to assess efficacy in terms of clinical symptoms. The study showed numerically less decline in CDR-SB for the elenbecestat 50 mg total arm as compared to placebo of a potentially clinically important difference, which was not statistically significant. Further, a similar magnitude and direction of differential in decline was observed in a post-hoc analysis of ADCOMS, Eisai’s newly developed assessment scale in the elenbecestat 50 mg total arm as compared to placebo. The study was not powered to show statistical significance compared to placebo on clinical symptoms.
Don’t Expect Much from YouTube Vids Labeled for Colon Cancer
One-quarter of 40 YouTube videos ostensibly about colorectal cancer featured “content of minimal or no relevance to colorectal cancer or screening,” according to a study presented here.
Among them: the most popular video that turned up on the site with a search for “colon cancer,” with some 3 million views.
“That was what was striking,” lead author Donelle Cummings, MD, of SUNY Downstate Medical Center in Brooklyn, N.Y., told MedPage Today. Cummings and colleague Prameela Rao, MD, presented their findings at Digestive Disease Week.
The pair searched YouTube for the terms “colon cancer” and “colon cancer screening” over 3 weeks last year, evaluating the top 20 most-viewed videos’ content and associations for both terms.
They did not find much educational content in videos with the most views, Cummings said.
“Providers must become familiar with web-based content and patients’ use of it for gathering information about colorectal cancer screening,” Cummings and Rao wrote in their poster. “Stakeholders must develop novel methods to educate and engage individuals using YouTube and similar platforms” to increase knowledge and screening rates.
About one-quarter of the videos included “expert or professional testimonial or narration,” the authors reported. Nearly half included information on colorectal cancer pathology, screening methods, and the benefits of screening. About one-quarter discussed risk factors, while 14 discussed signs and symptoms, and 14 treatments. Six discussed screening risks.
Two videos were actually advertisements.
Concerning the most-viewed video, Cummings noted it featured video of an endoscopy with limited dialogue — and nothing about colorectal cancer or screening.
Among the 40 videos, 16 were user-generated or independent. Cummings and Rao found seven posted by non-profits or public healthcare organizations, and five from national or international societies.
YouTube is second among all websites in total views, the authors noted, and “promotional messages have been shown to increase” screening rates. They added, “As individuals increasingly rely on web-based media to gather information, they may have difficulty finding quality content.”
So “it’s very important” for providers to be aware of what content is on popular sites, Cummings said, noting that educating patients is part of the job. “We have to kind of adapt with the times,” he added. Cummings advised providers look for quality online resources and steer patients to those, particularly any hosted by academic institutions and national societies.
Cummings encouraged stakeholders to work with YouTube to produce more certified videos on the site. The site has already begun displaying more certified videos recently “with high-quality content,” he said. “I’m encouraged by what I’ve seen lately.”
Osteoporosis Risk After Bariatric Surgery
Anatomical changes due to bariatric surgery can put patients at risk for mineral deficiencies and subsequent osteoporosis, and managing this risk can pose a challenge for healthcare providers.
“Many forms of bariatric surgery lead to malabsorption of calcium and vitamin D, which can cause secondary hyperparathyroidism in the absence of treatment,” Elaine W. Yu, MD, of Massachusetts General Hospital in Boston, explained to MedPage Today.
However, the degree of fracture risk following bariatric surgery varies based on the specific procedure.
“Mixed restrictive and malabsorptive procedures such as Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) are associated with an increased risk of fracture at osteoporotic sites, risk that starts to manifest between 2 and 5 years after surgery,” Anne Schafer, MD, of the University of California San Francisco and the San Francisco VA Healthcare System told MedPage Today. “Laparoscopic adjustable gastric banding (LAGB) appears not to increase fracture risk, at least in the short term, and it is not possible at this point to determine whether sleeve gastrectomy increases fracture risk.”
While sleeve gastrectomy may also cause bone loss, it’s perhaps to a lesser degree than BPD or RYGB, Yu said.
Schafer said that “the literature is largest and strongest for RYGB” mostly because it was the reigning bariatric procedure in popularity until recently.
“After RYGB, bone mineral density declines at the axial and appendicular skeleton, and there are detrimental effects on bone microstructure and estimated strength. Postmenopausal women seem to be particularly affected,” she noted.
As for screening, the joint guidelines released by the American Association of Clinical Endocrinologists (AACE), the Obesity Society, and American Society for Metabolic and Bariatric Surgery (ASMBS) state that DXA bone density scans are indicated both preoperatively and 2 years after bariatric surgery.
“In particular, I recommend screening patients who are at higher risk for low bone density, such as postmenopausal women, older men, and those with prior fragility fractures or a family history of osteoporosis,” Yu said.
This recommendation was echoed by Schafer, who added, “I believe DXA may be appropriate preoperatively in higher-risk patients, including postmenopausal women, men ages >50 years, and others with risk factors for osteoporosis. It could also be considered postoperatively, perhaps after 2 years, in select patients.”
In addition to screening bariatric surgery patients for bone changes, clinicians must also closely monitor calcium and vitamin D levels before and after surgery.
“Especially considering that patients with obesity are at high risk of vitamin D deficiency, one should measure serum 25-hydroxyvitamin D (25OHD) level and correct vitamin D deficiency preoperatively. Postoperatively, routine monitoring of serum 25OHD, calcium, albumin, and parathyroid hormone (PTH) levels is indicated. The recommended frequency of these measurements varies between guidelines, but one reasonable approach is to do routine biochemical screening every 6 months for the first 2 years and then annually,” Schafer said.
She recommended that providers refer to the guidelines of the ASMBS when considering calcium and vitamin D supplementation for these patients.
“Calcium citrate is preferred over calcium carbonate,” Schafer said, adding that it should be administered with split doses to achieve a total daily calcium intake — including diet plus supplements — of 1,200 to 1,500 mg per day in patients who underwent RYGB, sleeve gastrectomy, or LAGB. Patients who underwent BPD should aim to achieve a total intake of 1,800 to 2,400 mg daily, she added.
“These intakes may not be sufficient for a substantial proportion of patients, at least after RYGB and BPD, and thus monitoring with PTH (and 24-hour urinary calcium when appropriate) is important,” Schafer noted.
She also suggested that “a typical initial vitamin D supplement dose is 3,000 IU of vitamin D3 daily, with titration to serum 25OHD >30 ng/mL.”
Lifestyle modification after bariatric surgery is important for these patients in order to mitigate the adverse impact on their bones. Other recommendations include a diet sufficient in protein and regular physical activity.
In some bariatric surgery patients at a moderate to high fracture risk, antiresorptive osteoporosis therapies may also be appropriate. However, in order to minimize the risk of hypocalcemia, “an antiresorptive should be used only after vitamin D and calcium supplementation is deemed sufficient based on measurement of serum 25OHD, corrected calcium, PTH, and potentially 24h urinary calcium,” Schafer said, explaining that the parenteral route is preferred over oral treatment.
This recommendation was reinforced by Yu, who suggested that providers “avoid oral bisphosphonates due to theoretical problems with absorption and potential for increased risk of GI adverse effects. Intravenous bisphosphonates and/or denosumab could be cautiously considered as long as providers ensure appropriate calcium and vitamin D supplementation to avoid hypocalcemia.”
She also said that healthcare providers must emphasize to patients prior to bariatric surgery that calcium and vitamin D supplements are “lifelong requirements” following surgery.
“I want to reiterate the call for bone density screening in this population — in an analysis that we published, only around 10% of bariatric patients received bone density scans at any point after surgery,” Yu noted.
#ASCO18: Cancer therapy targeted at tumor genetics doubles survival
Using molecular tumor markers to select targeted therapy slowed cancer growth and doubled survival, according to a retrospective analysis of early experience with precision medicine.
Among 1,300 patients with at least one identified genetic alteration, those treated with a drug that targets the alteration had a 3-year overall survival (OS) of 15% as compared with 7% for patients who received nonmatched therapy. At 10 years, 6% of the patients treated with targeted therapy were still alive versus 1% of those who received conventional therapy, reported Apostolia-Maria Tsimberidou, MD, PhD, of the MD Anderson Cancer Center in Houston.
Progression-free survival, objective response rate, and clinical benefit rate all favored targeted therapy, she reported at the American Society of Clinical Oncology (ASCO) meeting.
“This is the first and largest study — with the longest follow-up — to assess the impact of precision medicine on survival across multiple cancer types,” she said during an ASCO press briefing. “Our findings show that molecular testing of tumors using next-generation sequencing can be used to optimize therapy and should be taken into consideration when selecting therapy for patients with difficult-t0-treat cancers.”
Apostolia-Maria Tsimberidou, MD, PhD, presenting the results
Noting that the results represented experience with patients treated as long ago as 2007, Tsimberidou said, “I am optimistic that in the next few years, we will dramatically improve outcomes for patients with cancer by increasing implementation of precision medicine.”
The advent of precision medicine transformed traditional paradigms for treating cancer, which focused on the type of cancer, growth kinetics, and other less specific methods of matching therapy to disease, said ASCO expert Catherine Diefenbach, MD, of NYU Langone Medical Center in New York City.
“This method of molecular profiling tumors and treating on the basis of actionable mutations is the wave of the future,” said Diefenbach. “Large-scale [studies] will bring these efforts to many, many more patients and will usher in new approaches to treating advanced cancer and hopefully improve overall survival.”
Tsimberidou reported long-term follow-up data from the Initiative for Molecular Profiling in Advanced Cancer Therapy (IMPACT). Begun in 2007, the study had a working hypothesis that selecting cancer therapy on the basis of patient’s tumor molecular analysis would lead to better outcomes as compared with the prevailing standard approaches.
The study involved patients with advanced-stage cancers for which no standard treatment options existed or who had incurable rare cancers. Study participants had been referred for molecular testing of tumor specimens, which might have involved a single gene during early stages of the testing program to as many as 50 in the later years.
If the test results showed an actionable mutation, patients were matched with targeted therapies, if available. If no appropriate targeted agents were available, patients received nonmatched treatment.
From 2007 to 2013, 3,743 patients underwent molecular testing, which revealed at least one targeted alteration in 1,307 patients. Subsequently, 711 of the patients were matched to a targeted therapy, and 596 received nonmatched therapy. The patients had received a median of four prior regimens, and 2.8% of the cohort had no prior treatment before referral for molecular evaluation. The most common types of cancer represented by the cohort were gastrointestinal (24.2%), gynecologic (19.4%), breast (13.5%), melanoma (11.9%), and lung (8.7%).
Tsimberidou reported that matched therapy resulted in an objective response rate of 16.2% versus 5.2% for nonmatched treatment. Additionally, 18.4% of matched patients and 14.7% of unmatched patients had stable disease for at least 6 months. Matched patients had a significantly higher clinical benefit rate (response plus stable disease: 34.9% versus 20.1%, P<0.001).
Patients who were matched to therapy had a median PFS of 4.0 months and median OS of 9.3 months, as compared with 2.8 and 7.3 months, respectively, for the unmatched population (HR 0.67, HR 0.72, P<0.001). By multivariate analysis, receiving nonmatched therapy was an independent predictor of worse survival (HR 1.30, 95% CI 1.16 to 1.46, P<0.001). Alterations in the PI3K/AKT/mTORpathway also were associated with worse survival (HR 1.25, 95% CI 1.10 to 1.42, P<0.001).
Investigation of the IMPACT strategy will continue in IMPACT 2, an ongoing prospective, phase II randomized trial comparing PFS in patients who received targeted therapy matched to tumor molecular characteristics versus treatment versus nonmatched therapy.
Although IMPACT and other studies have demonstrated the potential benefits of precision medicine and analysis of tumor genetics, the oncology community still has a lot to learn, cautioned Richard Schilsky, MD, ASCO chief medical officer.
“There’s a lot of this going on in routine clinical practice these days, and that’s probably a leap a little too far ahead of what the data will support, at least in the context of patients with far-advanced cancer,” he said. “Doing this in the context of a research program is a completely valid and important thing to do until we get the information we need about the circumstances under which these approaches actually work.”
Otis Brawley, MD, American Cancer Society chief medical officer, offered a more succinct cautionary assessment. “Precision medicine has given us some things, but it has promised a lot — which it has yet to deliver,” he said.
Tsimberidou disclosed relevant relationships with Baxter, Bayer, Boston Biomedical, EMD Serono, Foundation Medicine, IMMATICS, Karus Therapeutics, ONYX, Placon, and Stem Cells Inc. Co-authors disclosed multiple relevant relationships with industry.
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