Boeing (BA) is equipping mechanics with exoskeletons to increase their strength and speed and help reduce fatigue on repetitive tasks, according to a Reuters report from Eric Johnson and Tim Hepher. In a photo of employee Rob Gross, who “gets a boost from a gas-powered exoskeleton Boeing is using to boost productivity and safety,” an Ekso logo can be seen. Shares of small cap Ekso Bionics (EKSO) have jumped 17c, or 10%, to $1.91 in afternoon trading following the circulation of Reuters’ report.
https://thefly.com/landingPageNews.php?id=2857943
Friday, February 1, 2019
Personalized Medicine: Just Marketing?
“Personalized” medicine sounds appealing. Rather than just guessing at what medication to try, a genetic test can figure out, in advance, which medications will be effective and which medications are more likely to make you sicker.
Except it doesn’t work. It’s mostly marketing and hype.
The FDA has officially warned consumers and physicians that genetic tests sold to predict patient responses to medications shouldn’t be used. They’re not FDA approved, and in most cases, there’s no reason to think that these tests can accurately predict how a medication is metabolized or what it’s likely to do when you take it. These tests are being aggressively marketed to the general public and physicians, and they don’t deliver what they promise.
Medicines for conditions like depression, acid reflux, and heart disease have been highlighted by the FDA — though many other medicines have become targets for these tests, too. And these tests do reveal certain genetic “polymorphisms” (variations) that all of us carry, variations that affect the way medicines are metabolized and processed in our bodies.
The problem is that our knowledge about these polymorphisms is rapidly evolving, and it’s far from complete. It turns out that dozens or maybe hundreds of genes can have overlapping functions, and (with few exceptions) we don’t yet know all of the genes involved. And for each gene, there may be hundreds or thousands of variations in the general public. Or maybe, some of us have a unique variant that hasn’t been seen before. These companies have no way to test the gene variants to know their function. They rely on proprietary databases, riddled with incomplete data and assumptions.
Just one example: When the MTHFR gene and its variants were first described, it seemed like MTHFR polymorphisms could have wide-ranging and significant health effects. It turned out that’s completely wrong. MTHFR “variations” are so common in the general public that it’s fair to say we all have polymorphisms, and almost none of these have any clinical importance. Even the 23andMe company, which makes money selling genetic tests, discourages MTHFR testing, saying, “Despite lots of research — and lots of buzz — the existing scientific data doesn’t support the vast majority of claims that common MTHFR variants impact human health.” Still, many families are still relying on misguided MTHFR testing pushed by naturopaths and chiropractors to make health decisions. And this is just one of the hundreds of genes these kinds of tests rely on.
Genetics shows great promise, and I think the future includes a big role for genetic testing. But we don’t have the knowledge to use the results of these tests to better guide therapy. But that doesn’t mean that therapeutic decisions, now, are entirely guesswork. Reviewing a family history and the exact nature of a problem often gives physicians some good clues to help guide decisions. I know, that sounds old-fashioned. But talking and listening remain the best ways for docs and patients to work together to make the best decisions.
Roy Benaroch, MD, is a pediatrician who blogs at the Pediatric Insider. He is also the author of A Guide to Getting the Best Health Care for Your Child and the creator of The Great Courses’ Medical School for Everyone: Grand Rounds Cases.
Cath procedure helped women conceive without pills or IVF
A relatively fast outpatient procedure helped infertile women become pregnant – without the need for pills or in vitro fertilization, researchers said here.
Using micro-catheters and a 0.018-inch guide-wire, doctors can perform proximal fallopian tube recanalization in less than the time it takes to watch a feature length movie, reported Jeff Wang, BS, a fourth-year medical student at Chicago Medical School.
At the 2019 International Symposium on Endovascular Therapy, Wang said his review of hospital records found that of 66 women for whom complete records were available, 21 pregnancies occurred, and the median time to pregnancy in these women was 4 months.
“The use of micro-catheters and wires that can be maneuvered in a minimally-invasive manner should make it a first-line use for removing fallopian tube proximal occlusions for women having fertility problems,” Wang told MedPage Today.
His retrospective review overall included 160 patients over the course of 24 years who were treated by Rush Medicine of Chicago. “We have one of the larger datasets out there and it confirms this is a minimally-invasive procedure that has pretty good outcomes. It also shows how obstetricians and gynecologists can work together with interventionalists,” Wang said.
“There is a subset of women – about 30% of the women who report fertility problems — who have proximal occlusions of their fallopian tubes,” he said. “These occlusions can be mucus or debris or a contamination of mucus and debris which build up over time. Which women are at risk for this occurring has not yet been fully explored. It could be they have a history of chronic infection or they could just be unlucky.”
He said the women are all referrals from specialists. “Usually, you have a couple who come to the ob/gyn office with problems of getting pregnant,” he said. “These patients are then referred to a reproductive endocrinologist/fertility specialist.”
In an outpatient procedure, interventionalists employ a micro-catheter to perform hysterosalpingography, and, if necessary, the wire is deployed to remove debris from the tube. “It can take a half hour to 90 minutes, depending on anatomy or whether both tubes need to be opened,” Wang said. “We use a high pressure hysterosalpingogram to determine if contrast is getting into the fallopian tubes. Sometimes this itself will unblock the occlusion. If we can’t see the contrast, we know there is a blockage. The procedure is all done through the vaginal canal. Some women experience some post-procedural pain that can be managed with medication.”
He said that all the women in the study were seeking to get pregnant. “But so far we have only been able to gather follow-up data on 66 of the patients, and 21 of them or 32% have gotten pregnant. Our data only tells us that these patients achieved fertilization. We do not yet have data on live births. Live births are part of a different dataset that we haven’t flushed out yet.”
In commenting on the study, Francisco Contreras, MD, an interventional radiologist and associate professor of radiology at Florida State University, University of Central Florida, and Florida Hospital, Orlando, told MedPage Today, “We, as interventional radiologists, have been successful in using these techniques to recanalize the fallopian tubes, and I think as more and more physicians and patients learn of these procedures it is likely that this will be done more frequently.” He suggested that a 32% pregnancy rate as described in the study would be considered a good result.
Contreras noted that undergoing the minimally-invasive procedure would not preclude other attempts at pregnancy down the line, such as in vitro fertilization.
- Prior to the treatment, Wang said 89 women had no patent tubes, but after the procedure 72 of these women achieved bilateral patency; 14 achieved unilateral patency; three women still had no patent tubes.
- In the 67 women who presented with one blocked fallopian tube, bilateral patency was achieved in 61 women; six women remained with one open tube.
- Four women had patent fallopian tubes but underwent the procedure to remove blockages. All still had bilateral patency following the procedure.
Wang said the interventionalists achieved technical success in 319 of 341 tubes they attempted to recanalize.
“We are now seeking to get long-term data and to increase the sample size, and it is important to get live birth outcomes as well,” he said.
Wang and Contreras disclosed no relevant relationships with industry.
Primary Source
International Symposium on Endovascular Therapy
Consumer Reports, Industry Square Off Over Metals in Juice
The fruit juice industry hit back at Consumer Reports, the product testing and ratings publication, following its report on Wednesday that many well-known juice products contain enough arsenic, lead, and cadmium that they should be avoided.
Consumer Reports said 21 of 45 juice products it tested had “concerning” levels of at least one of these heavy metals. One such product, Trader Joe’s Fresh Pressed Apple Juice, exceeded 15 parts per billion (ppb) for arsenic — well above a proposed, though not yet official, federal standard of 10 ppb. Two Welch’s products contained lead at more than 5 ppb.
However, the report did not disclose the specific concentrations found for most of the products, nor did it explain what constituted “concerning” levels. In a statement released Thursday, the Juice Products Association seized on those omissions to accuse Consumer Reports of “raising unnecessary alarm.” The publication’s classification of some products as being “potentially harmful” was “without any scientific basis,” the industry group said.
“There is no scientific evidence indicating that the presence of trace levels of heavy metals in juice has caused any negative health outcomes among individuals at any life stage,” the group declared, although it acknowledged that “trace, harmless levels of these substances may exist in juice, and other foods.”
The group cited the FDA’s Total Diet Study to support its assertion that these “trace” levels are harmless. However, that effort merely tests foods for concentrations of various contaminants without determining whether they are unhealthy.
News reports about the dispute pointed out that toxicologists generally accept that no threshold for harm has been established for heavy metals in foods, especially for children. NPR, for example, spoke with an American Academy of Pediatrics committee member, Aparna Bole, MD, of Cleveland’s University Hospitals, who took Consumer Reports’ side: “We know there are no safe levels of exposure to these heavy metals.”
And the director of the National Institute of Environmental Health Sciences told NPR that lead may be harmful at levels below 1 ppb.
Heart Attack But Not Dementia Reduced With Tight Blood Pressure Control
Target Audience and Goal Statement:
Cardiologists, vascular medicine specialists, neurologists, geriatricians, internists, and family medicine physicians
The goal of the study was to determine whether reducing systolic blood pressure (BP) in older adults, ages 50 and up, who have hypertension but without diabetes or stroke, could reduce risk of dementia and/or mild cognitive impairment (MCI).
Questions Addressed:
- Does reducing systolic BP in adults older than age 50 reduce the risk of dementia and/or mild cognitive impairment and if so, by how much?
- Is the reduction of BP in this patient population safe?
- Are there any differences between subgroups in the effects of BP reduction on incident dementia and/or MCI?
Study Synopsis and Perspective:
Aggressively reducing blood pressure in hypertensive older adults reduced dementia risk by 17%, which was not statistically significant, and it reduced MCI by 19%, which was statistically significant, according to the SPRINT MIND study, reported in JAMA.
The SPRINT MIND study, a randomized trial conducted at 102 U.S. and Puerto Rico sites, compared the effects of treating hypertensive adults, ages 50 and up, to reach a systolic blood pressure (SBP) goal of <120 mm Hg, with treating them to a goal of <140 mm Hg. The primary outcome measure was incidence of probable dementia. Although this was reduced by 17% among patients with the lower target, it was not statistically significant (HR 0.83, 95% CI 0.67-1.04) and thus the primary endpoint was missed, according to author Jeff Williamson, MD, MHS, of the Wake Forest School of Medicine in Winston-Salem, North Carolina, and colleagues.
But attaining intensive blood pressure control did show statistically significant benefits in secondary outcomes, including a 19% lower rate for MCI (HR 0.81, 95% CI 0.69-0.95).
The mean SBP at baseline was 139.7 mm Hg, and the median Montreal Cognitive Assessment (MoCA) score was 23 (interquartile range, 20-26). Before the decision to terminate the trial, the mean SBP in the intensive treatment group was 121.6 mm Hg and 134.8 mm Hg in the standard treatment group, for a mean between-group difference of 13.3 mm Hg.
In the study, researchers included 9,361 individuals ages ≥50 who had baseline blood pressure — treated or untreated — from 130 to 180. All participants also had at least one additional cardiovascular risk factor, but not diabetes and no history of stroke; the average age in the study was 67.9. About 30% of the cohort was African American and 10% Hispanic. The median follow-up time was 5.11 years.
During this follow-up time, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1,000 person-years). Intensive BP control significantly reduced the risk of MCI (14.6 vs 18.3 cases per 1,000 person-years), as well as the combined incidence of MCI or probable dementia (20.2 vs 24.1 cases per 1,000 person-years; HR 0.85; 95% CI 0.74-0.97).
Participants received anti-hypertensive medications to help achieve their assigned blood pressure target, mostly generic drugs. The trial was not designed to test a specific drug. “SPRINT used a quasi-pragmatic approach with suggestions for treatment choice, but practitioners approached systolic blood pressure control individually, and most participants were taking multiple drugs,” noted Kristine Yaffe, MD, of the University of California San Francisco, in an accompanying editorial.
SPRINT MIND was a substudy of the NIH-funded Systolic Blood Pressure Intervention Trial (SPRINT), which aimed to determine whether aggressively lowering blood pressure could protect the heart, kidney, and brain over 5 years. Initial apparent success of the heart disease portion — although questions were later raised about the trial’s design and conduct and how results should be applied — led to the trial’s early termination at 3.3 years.
This made the study too short to definitively answer the dementia question, Williamson said. As a result, the Alzheimer’s Association announced in late January 2019 that it is funding Williamson’s group for SPRINT MIND 2.0, a 2-year extension.”Because dementia is a much more slowly progressive disease from no impairment to impairment, our hope is that with 2 more years of follow-up, SPRINT MIND will accrue the number of new cases of dementia that we originally planned for so that we can definitively answer this question,” Williamson added.
“The primary outcome was negative in the SPRINT MIND trial, but we’re very encouraged by the positive trend,” Maria Carrillo, PhD, the Alzheimer’s Association chief science officer, told MedPage Today. “And we are incredibly compelled by the secondary outcome of mild cognitive impairment being reduced by 19%. We think that with an extended time frame and an additional opportunity for follow-up, we may very well see that dementia outcome is positive.”
The authors noted that the incidence of probable dementia “was likely underestimated in both treatment groups because of incomplete ascertainment.”
They also observed that there has been controversy surrounding the benefits and risks associated with lowering SBP to below 150 mm Hg, such as the possibility of hypotension and cerebral hypoperfusion resulting in negative effects on the brain. The authors stress that their trial “demonstrates no such negative effect; specifically, these results importantly show that intensive BP control did not result in harm to cognition after a median intervention period of 3.34 years and an overall median follow-up of 5.11 years.” To the contrary, they view this trial as evidence, the first in any study, of benefit for reducing SBP in the reduction of MCI occurrence, a known risk factor for dementia.
Study limitations include early termination of the study which reflects a probable loss of power to detect an effect on dementia beyond that point. As well, patients with common comorbidities including type 2 diabetes, previous stroke, advanced kidney disease, or heart failure were excluded. The study did not adjudicate baseline cognitive status, and there was no way to determine the relative effect of specific anti-hypertensive medications on MCI or dementia.
There was also limited power to detect differences among race/ethnic groups; a recent study mentioned by Yaffe reported that older black adults may show greater effects of SBP control on cognitive outcomes. “This finding requires further investigation,” she observed.
Source References: JAMA 2019; DOI:10.1001/jama.2018.21442
Editorial: JAMA 2019; DOI:10.1001/jama.2019.0008
Study Highlights: Explanation of Findings
The study found that aggressively reducing blood pressure in hypertensive older adults reduced dementia risk by 17%, which was not statistically significant, and it reduced MCI by 19%, which was statistically significant. Many observational studies have linked hypertension to dementia, Yaffe pointed out in her editorial.
“How does one interpret a secondary endpoint in a trial that fails to win on the primary endpoint? With great circumspection,” observed Sanjay Kaul, MD, of Cedars-Sinai Medical Center in Los Angeles, who was not involved in the research.
“Hence the caveat from the investigators: ‘There was no adjustment of the significance threshold for the secondary or other endpoints; because of the potential for type I error, the findings from these analyses should be considered exploratory,'” Kaul told MedPage Today.
But even if the dementia results are positive, how that will translate into clinical practice is up for debate. “The relation of blood pressure — and in particular level and change in blood pressure — to brain function is complex,” noted Zoe Arvanitakis, MD, of Rush University Medical Center in Chicago.
While SPRINT MIND adds important information to this puzzle, more research needs to be done across a range of blood pressures, in a range of ages, using different outcomes beyond diagnostic dementia classification, Arvanitakis told MedPage Today.
A recent study of nearly 1,300 older people at autopsy showed that faster declining systolic blood pressure was associated with an increased number of brain infarcts and more severe cerebral vessel pathologies, she noted, and much research is needed to “better understand the potential benefits of intensive blood pressure treatment, as well as the potential risks.”
Like any other clinical trial, the results of SPRINT MIND should be interpreted in the context of the population it studied, added Behnam Sabayan, MD, PhD, of Northwestern University in Chicago.
“SPRINT excluded individuals who had diabetes, history of stroke, and those who are residing in nursing homes,” Sabayan told MedPage Today. “This means that frail individuals with highest burden of cerebrovascular pathologies were not necessarily a part of this study, and intensive blood pressure reduction in those subjects should be exercised with caution since it can put them at risk for brain hypoperfusion, falls, kidney impairment and might introduce further risk for subsequent strokes.”
The MCI finding in SPRINT MIND also needs a more careful look, Kaul suggested. “In a sensitivity analysis that accounts for multiple imputation for missing data for time to first mild cognitive impairment, the difference was not significant,” he said.
“And even if we were to take the results at face value, it is unproven whether lowering the risk of mild cognitive impairment will translate into reduced risk of progression to dementia or Alzheimer’s disease,” Kaul added.
Primary Source
JAMA
Secondary Source
JAMA
Additional Source
MedPage Today
Source Reference: George J “SPRINT MIND: What Have We Learned?” 2019.
Dramatic Increase in Teens’ Smoking Risk With Previous Vaping
Youth whose first use of a tobacco product was electronic cigarettes were more likely to initiate cigarette smoking over 2 years of follow-up in a newly reported study.
Prior e-cigarette use was associated with a more than four-fold greater risk of ever smoking cigarettes and three-fold greater risk of current cigarette use in the prospective cohort study.
Findings from the nationally representative study, published online in JAMA Network Open, add to the growing evidence linking e-cigarette use to an increased risk for initiating cigarette smoking among youth, especially among low-risk teens.
Kaitlyn M. Berry, MPH, of Boston University School of Public Health, and colleagues, concluded that the findings highlight the need for “aggressive regulation” to restrict access to e-cigarettes among teens.
Several recent studies have raised the alarm about an elevated risk of smoking initiation among teen e-cigarette users, including a 2017 meta-analysis that found that teens and young adults who used e-cigarettes had more than three times the odds of later cigarette use and more than four times the odds of current cigarette smoking.
This analysis led the National Academies of Sciences to conclude in a 2018 report that there is “substantial evidence” that e-cigarette use increases the risk for cigarette-smoking tobacco-naive youth.
But in an email exchange with MedPage Today, Berry explained that many of the prior studies may have been subject to methodological limitations because they started with a sample of youth who were never cigarette users, assessed their e-cigarette use at that early time point, and then reviewed their smoking status after a year of follow-up.
“By removing cigarette users at the beginning, this design may overlook youth who started with e-cigarettes and already made the transition to cigarette smoking,” she said. “Additionally, the design may misclassify youth who started vaping between the two time points.”
The design of the new study, which centers around a youth’s very first tobacco product use, allowed the researchers to create what Berry described as “a loose timeline of the order of products used, that, in theory, avoids these potential issues.”
The researchers analyzed data from three waves of the nationally representative Population Assessment of Tobacco and Health (PATH) Study (2013-2016) in their effort to evaluate the association between prior e-cigarette use and use of other non-cigarette tobacco products with later cigarette initiation over a roughly 2-year period.
The sample included 6,123 respondents (49.5% female, 54.1% non-Hispanic white) with a mean age of 13.4 (1.2 years) who were tobacco-naive at baseline.
A total of 8.6% reported e-cigarettes as their first tobacco product, while 5.0% reported using another non-cigarette product first (3.3% reported using cigarettes first).
Cigarette use at wave 3 was higher among prior e-cigarette users (20.5%) compared with youths with no prior tobacco use (3.8%).
Among the other main findings:
- Prior e-cigarette use was associated with more than four times the odds of ever cigarette use (OR 4.09, 95% CI 2.97-5.63) and nearly three times the odds of current cigarette use (OR 2.75, 95% CI 1.60-4.73), compared with no prior tobacco use
- Prior use of other tobacco products was similarly associated with subsequent ever cigarette use (OR 3.84, 95% CI 2.63-5.63) and current cigarette use (OR 3.43, 95% CI 1.88-6.26), compared with no prior tobacco use
- At the population level, the analysis indicated that the fraction of ever cigarette use attributable to prior e-cigarette use was 21.8% (an estimated 178,850 youths) and 15.3% of current cigarette use (43,446 youths) among U.S. youths ages 12 to 15 may be attributable to prior e-cigarette use
Nine variables were used to categorize the respondents into risk groups, including alcohol, marijuana, and prescription drugs without a prescription. The association of prior e-cigarette use with cigarette initiation was found to be strongest among youth categorized as low-risk (OR 8.57, 95% CI 3.87-18.97).
The researchers concluded that this finding “raises concerns that e-cigarettes may re-normalize smoking behaviors and erode decades of progress in reducing smoking among youths.”
Grant funding for the research was provided by the National Institutes of Health, the National Heart, Lung, and Blood Institute, and the National Cancer Institute.
Researcher Andrew Stokes reported receiving research grants from Johnson & Johnson not associated with this study.
Novartis eyes blockbuster launches for 2018-20, including Kymriah
As Novartis shakes off its Alcon eye business and the loss of two high-profile executives, chief Vas Narasimhan has outlined the Swiss drugmaker’s roster of 14 blockbuster launches, a bulk of which are expected to win approval between this year and 2020. The drugs included in the list are largely familiar, but the inclusion of the company’s pioneering CAR-T therapy Kymriah, whose adoption has been wobbly due to manufacturing woes, will raise some eyebrows.
In 2017, Novartis spent a hefty $9 billion on R&D, making it one of the top spenders in global biopharma. Investors expect to see the company to now get bang for its buck. Last November, the company used it R&D review to highlight 26 blockbuster contenders in its arsenal and offer a rosy picture of things to come after suffering a few knocks — the FDA rejecting its heart drug, and the company abandoning its attempt at a Rituxan copycat.
Since then, the company has seen good days and bad. On the positive front, its gene therapy for SMA secured the FDA’s priority review, and its sickle cell drug won breakthrough therapy status. The drugmaker also swallowed a cell and gene therapy manufacturer in an attempt to unclog the commercial rollout for Kymriah. In a first for a multinational pharmaceutical company, Novartis’ Sandoz unit tied up with Canadian medical cannabis producer Tilray, a landmark endorsement of the controversial plant. On Wednesday, as part of its full-year 2018 results, the drugmaker said four newer products — including Cosentyx and Entresto — in its roster of medicines achieved blockbuster status in 2018.
On the other end of the scale, Novartis has also suffered a number of setbacks in the last quarter of 2018. For instance, its migraine drug Aimovig — billed as a blockbuster and partnered with Amgen — was refused endorsement by the UK’s NICE, months after the agency declined to give the nod for Kymriah. Two top executives — CAR-T chief David Lebwohl and oncology head Liz Barrett — also left the drugmaker to take top positions in small biotechs. And J&J dealt Novartis a blow when its psoriasis drug Tremfya beat the dominant Cosentyx in a head-to-head study.
On the other end of the scale, Novartis has also suffered a number of setbacks in the last quarter of 2018. For instance, its migraine drug Aimovig — billed as a blockbuster and partnered with Amgen — was refused endorsement by the UK’s NICE, months after the agency declined to give the nod for Kymriah. Two top executives — CAR-T chief David Lebwohl and oncology head Liz Barrett — also left the drugmaker to take top positions in small biotechs. And J&J dealt Novartis a blow when its psoriasis drug Tremfya beat the dominant Cosentyx in a head-to-head study.
2018
AIMOVIG — The migraine drug forms part of a new crop of biologics targeting the CGRP protein that transmits pain signals into the brain. The drug was the first to win approval in 2018, and within months rival treatments from Lilly and Teva were also given regulatory nods. All three have demonstrated similar efficacy and safety in trials. Like its rivals, the drug is priced at $575 per month and has been pegged as a potential blockbuster. Following the NICE setback, reports suggested Aimovig was excluded from pharmacy benefits manager CVS’ formulary in the United States. This will be a blow, but there are other PBMs on the block.
KYMRIAH — The pioneering CAR-T drug was FDA approved amidst great fanfare in 2017, and since then the FDA has expanded its use in the United States and the EC also approved the drug last August. NICE refused to endorse the pricey drug. Meanwhile, rivals such as Gilead’s Yescarta have emerged, and Kymriah sales have suffered due to manufacturing issues. In the fourth quarter, the drug generated a paltry $28 million. However, Novartis is doing its best to shore up manufacturing, having bought cell and gene therapy manufacturer CellforCure.
LUTATHERA — The cancer drug, which came with Novartis’ $4 billion acquisition of Advanced Accelerator Applications in 2017, paid off handsomely in early 2018 after the FDA gave it a quick OK. Novartis reported an 11% jump in oncology revenue in the fourth quarter, driven partly by Lutathera sales of $81 million.
2019
BYL719 — Otherwise known as alpelisib, the PI3K inhibitor nearly doubled progression-free survival in a third of patients with a hard-to treat form of breast cancer last October. Other drugs in this class, including Roche’s taselisib, have largely crashed and burned due to safety concerns.
MAYZENT — Expected to launch this year, the MS drug also known as siponimod is critical for the company as one of its top sellers Gilenya has generic competition looming. Company officials have previously described the drug’s data in glowing terms, and analysts have concurred, offering a $3 billion peak sales projection for the treatment.
RTH258 — The eye drug has been built up as a rival to Regeneron’s flagship blockbuster injection Eylea and CEO Narasimhan has gone so far as to say RTH258 is “consistently superior” to Eylea, after conducting retrospective analyses of late-stage data last year. Eylea has been untouchable for more than a decade, so it is up to Novartis to prove otherwise.
ZOLGENSMA — The gene therapy is currently under FDA review and the agency is expected to announce its decision in May. In its review posted in December, ICER suggested the Zolgensma — with a list price of $2 million — would offer more cost-effective benefit in the long run versus rival Biogen’s Spinraza. However, the Swiss drugmaker has suggested a price of $4 million for the curative therapy, which it acquired via a $8.7 billion takeover of AveXis, may be justified.
2020
COSENTYX — The psoriasis drug that became a blockbuster in 2016 is one of Novartis’ key drugs, and the drugmaker is working on expanding the IL-17A inhibitor’s market by including patients with psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondylarthritis (nrAxSpA). Pivotal data are expected later this year and, if positive, will be followed by a marketing application before the end of this year.
ENTRESTO — The medicine is another top seller for Novartis and is currently approved for HFrEF (formerly known as systolic heart failure) — in these patients the heart muscle does not contract effectively, reducing the level of oxygen-rich blood pumped into to the body. Initially a slow moving product hampered by physicians reluctant to adopt a new therapy and insurers who balked at its price, Entresto is now comfortably a blockbuster product. The drug is now under evaluation for HFpEF (also referred to as diastolic heart failure) — a now larger group of patients whose heart muscle contract normally but ventricles do not relax as they should during ventricular filling. Data from the trial PARAGON-HF are expected in the third quarter of 2019.
INC280 — Otherwise known as capmatinib, the MET inhibitor was licensed to Novartis from Incyte in 2009. Mid-stage data on the drug in certain patients with the most common form of lung cancer (NSCLC), presented last October, showed INC280 induced an ORR of 72% in treatment-naive patients and about 39% in previously treated patients. Novartis is expected to submit a marketing application later this year.
OMB157 — Other than the approved Gilenya and Mayzent — which is currently under review — ofatumumab (OMB157) is another drug Novartis is hoping to use in MS. The drug, already sold as Arzerra, has caused a number of problems for Novartis as a treatment for leukemia — the drugmaker was forced to pull it off the market outside the US as competition heated up. Novartis thinks it can repurpose the drug for MS, an indication for which it is currently being investigated in two Phase III studies.
PDR001 COMBO — PDR001, also called spartalizumab, is Novartis’ PD-1 inhibitor and is being tested in a number of cancers. A late-stage study testing the drug in combination with Novartis’ approved cancer drugs — Tafinlar and Mekinist — in patients with metastatic melanoma is ongoing.
QVM149 — The asthma drug is currently being tested against standard triple combination therapy in a late-stage study in uncontrolled asthmatics — the trial is expected to be completed this year.
SEG101 — Expected to launch in 2020, the sickle cell disease drug has secured the FDA’s breakthrough therapy designation earlier this month. After a delay in 2018, a marketing application for the drug is expected this year.
AIMOVIG — The migraine drug forms part of a new crop of biologics targeting the CGRP protein that transmits pain signals into the brain. The drug was the first to win approval in 2018, and within months rival treatments from Lilly and Teva were also given regulatory nods. All three have demonstrated similar efficacy and safety in trials. Like its rivals, the drug is priced at $575 per month and has been pegged as a potential blockbuster. Following the NICE setback, reports suggested Aimovig was excluded from pharmacy benefits manager CVS’ formulary in the United States. This will be a blow, but there are other PBMs on the block.
KYMRIAH — The pioneering CAR-T drug was FDA approved amidst great fanfare in 2017, and since then the FDA has expanded its use in the United States and the EC also approved the drug last August. NICE refused to endorse the pricey drug. Meanwhile, rivals such as Gilead’s Yescarta have emerged, and Kymriah sales have suffered due to manufacturing issues. In the fourth quarter, the drug generated a paltry $28 million. However, Novartis is doing its best to shore up manufacturing, having bought cell and gene therapy manufacturer CellforCure.
LUTATHERA — The cancer drug, which came with Novartis’ $4 billion acquisition of Advanced Accelerator Applications in 2017, paid off handsomely in early 2018 after the FDA gave it a quick OK. Novartis reported an 11% jump in oncology revenue in the fourth quarter, driven partly by Lutathera sales of $81 million.
2019
BYL719 — Otherwise known as alpelisib, the PI3K inhibitor nearly doubled progression-free survival in a third of patients with a hard-to treat form of breast cancer last October. Other drugs in this class, including Roche’s taselisib, have largely crashed and burned due to safety concerns.
MAYZENT — Expected to launch this year, the MS drug also known as siponimod is critical for the company as one of its top sellers Gilenya has generic competition looming. Company officials have previously described the drug’s data in glowing terms, and analysts have concurred, offering a $3 billion peak sales projection for the treatment.
RTH258 — The eye drug has been built up as a rival to Regeneron’s flagship blockbuster injection Eylea and CEO Narasimhan has gone so far as to say RTH258 is “consistently superior” to Eylea, after conducting retrospective analyses of late-stage data last year. Eylea has been untouchable for more than a decade, so it is up to Novartis to prove otherwise.
ZOLGENSMA — The gene therapy is currently under FDA review and the agency is expected to announce its decision in May. In its review posted in December, ICER suggested the Zolgensma — with a list price of $2 million — would offer more cost-effective benefit in the long run versus rival Biogen’s Spinraza. However, the Swiss drugmaker has suggested a price of $4 million for the curative therapy, which it acquired via a $8.7 billion takeover of AveXis, may be justified.
2020
COSENTYX — The psoriasis drug that became a blockbuster in 2016 is one of Novartis’ key drugs, and the drugmaker is working on expanding the IL-17A inhibitor’s market by including patients with psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondylarthritis (nrAxSpA). Pivotal data are expected later this year and, if positive, will be followed by a marketing application before the end of this year.
ENTRESTO — The medicine is another top seller for Novartis and is currently approved for HFrEF (formerly known as systolic heart failure) — in these patients the heart muscle does not contract effectively, reducing the level of oxygen-rich blood pumped into to the body. Initially a slow moving product hampered by physicians reluctant to adopt a new therapy and insurers who balked at its price, Entresto is now comfortably a blockbuster product. The drug is now under evaluation for HFpEF (also referred to as diastolic heart failure) — a now larger group of patients whose heart muscle contract normally but ventricles do not relax as they should during ventricular filling. Data from the trial PARAGON-HF are expected in the third quarter of 2019.
INC280 — Otherwise known as capmatinib, the MET inhibitor was licensed to Novartis from Incyte in 2009. Mid-stage data on the drug in certain patients with the most common form of lung cancer (NSCLC), presented last October, showed INC280 induced an ORR of 72% in treatment-naive patients and about 39% in previously treated patients. Novartis is expected to submit a marketing application later this year.
OMB157 — Other than the approved Gilenya and Mayzent — which is currently under review — ofatumumab (OMB157) is another drug Novartis is hoping to use in MS. The drug, already sold as Arzerra, has caused a number of problems for Novartis as a treatment for leukemia — the drugmaker was forced to pull it off the market outside the US as competition heated up. Novartis thinks it can repurpose the drug for MS, an indication for which it is currently being investigated in two Phase III studies.
PDR001 COMBO — PDR001, also called spartalizumab, is Novartis’ PD-1 inhibitor and is being tested in a number of cancers. A late-stage study testing the drug in combination with Novartis’ approved cancer drugs — Tafinlar and Mekinist — in patients with metastatic melanoma is ongoing.
QVM149 — The asthma drug is currently being tested against standard triple combination therapy in a late-stage study in uncontrolled asthmatics — the trial is expected to be completed this year.
SEG101 — Expected to launch in 2020, the sickle cell disease drug has secured the FDA’s breakthrough therapy designation earlier this month. After a delay in 2018, a marketing application for the drug is expected this year.
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