Epigenomics AG (Frankfurt Prime Standard: ECX, OTCQX: EPGNY), announced today that the Centers for Medicare & Medicaid Services (CMS) published a preliminary rate of $192 per Epi proColon test. Epi proColon is the first and only FDA-approved blood-based test for colorectal cancer screening. A press release with further details will be published on Monday, June 11, 2018.
Saturday, June 9, 2018
CDC Report Says Tobacco Use Declining in Teens
According to newly released figures from the CDC, tobacco use continued to decline among high school and middle school students in the U.S. in 2017. But the new data may fail to capture use of an electronic cigarette brand that has become hugely popular among teens, a separate report suggests.
Last year, current use of e-cigarettes among high school students was similar to that reported in 2016 and significantly lower than in the previous 2 years, according to data from the CDC’s National Youth Tobacco Survey (NYTS).
E-cigarettes remained the most widely used tobacco product among teens, but cigars overtook conventional cigarettes as the second most popular tobacco product among youth in 2017.
The new report outlining trends in youth tobacco use from 2011 to 2017 was published Thursday in the CDC’s Morbidity and Mortality Weekly Report.
“The big news here is that we have seen a considerable decline in all forms of youth tobacco product use since 2011,” Brian King, PhD, of the CDC’s Office on Smoking and Health, told MedPage Today.
“There are well over a million fewer kids using any form of tobacco product. However, on balance, the bad news is that there are still 3.5 million kids in the U.S. using some type of tobacco product and among those, half are using two or more tobacco products.”
Nearly one in five high school students and one in 18 middle school students reported current use of any tobacco product in 2017, compared with nearly one in four high school students and one in 13 middle school students in 2011.
In a statement following the report’s release, FDA Commissioner Scott Gottlieb, MD, said: “While fewer youth are using cigarettes and other combustible tobacco products, we must do more to address the disturbingly high number of youth who are using e-cigarettes and vaping products. We must not lose sight of the fact that for the past several years, e-cigarettes have been the most commonly used tobacco product among both middle and high school students and a total of 2.1 million youth used e-cigarettes in 2017.”
In 2017, 9.9% of female high school students and 13.3% of male high school students reported current use of e-cigarettes, which would mean that slightly over one in 10 high school students in the U.S. (11.7%) used e-cigarettes on a regular basis.
But a report published May 31 in Tobacco Control questions the accuracy of national teen tobacco use surveys and suggests that the current prevalence of e-cigarette use may be much higher than the NYTS data suggest.
The report examined the explosive growth of the electronic cigarette brand JUUL, which entered the market in the U.S. in 2015 and now commands more than 50% of the market.
Although sales of e-cigarettes to minors are prohibited by law, the FDA recently acknowledged that the brand has become wildly popular with underage users,announcing a crackdown on illegal sales.
According to lead researcher Jidong Huang, PhD, of Georgia State University School of Public Health in Atlanta, one reason the latest CDC figures may not accurately reflect current teen e-cigarette use is that the survey was conducted early in 2017 and the main growth in JUUL sales occurred in the mid- to latter months of 2017.
Huang told MedPage Today that many teens who use JUUL also may not consider the products to be e-cigarettes, since they look like USB flash drives rather than like traditional cigarettes or vaping devices.
“We believe national surveys like the one in the report are not capturing the use of JUUL — not because teens are lying, but because they don’t see these products as e-cigarettes,” he said.
King said the lack of progress in reducing e-cigarette use among teens is concerning, regardless of whether usage stalled or increased in 2017.
“Either way, it represents a non-continuation of the decline that we saw between 2015 and 2016. It also illustrates the importance of redoubling our efforts to reduce the use of these products among youth, which we know have health effects in this population.”
In a report on youth and e-cigarettes released in 2016, the U.S. Surgeon General found that youth and young adults are uniquely vulnerable to the long-term consequences of exposing the brain to nicotine, concluding that use of nicotine in any form is unsafe.
In a statement released Thursday afternoon, American Heart Association CEO Nancy Brown called the new e-cigarette data “worrisome.”
“The decline disclosed by the 2016 survey appears to have stalled last year,” she said. “Our greatest fear is that this may be a warning sign of a reversal, and in the coming years we may see a disturbing rise in the number of middle and high school students who smoke e-cigarettes.”
Brown called on the FDA to “crackdown on sloppy enforcement of age restrictions on tobacco sales” and remove flavored e-cigarettes and other flavored tobacco products that appeal to teens and young adults from the market.
“Vaping has become a scary trend among the youth in this country and the public is starting to take notice,” she said, citing San Francisco voters’ move earlier in the week to become the first city in the nation to ban all flavored tobacco products.
“We hope this action got the attention of the FDA and will spur the agency to take similar steps nationwide before our children repeat the tragic mistakes of prior generations and become lifelong tobacco addicts.”
Primary Source
CDC Morbidity and Mortality Weekly Report
Worse Depression Trajectory in Old Age
Major depressive disorder (MDD) may be more persistent for older individuals, a longitudinal study found.
Within a cohort of 18- to 88-year-old patients, older age was tied to a worse 2-year course of depression across several variables, reported Roxanne Schaakxs, PhD, of the VU University Medical Center in Amsterdam, and colleagues in The Lancet Psychiatry.
Older patients were more likely to have a diagnosis of major depression after 2 years (OR 1.08, 95% CI 1.00-1.17) and to have chronic symptoms (OR 1.24, 95% CI 1.13-1.35). They were also less likely to achieve remission of symptoms (HR 0.91, 95% CI 0.87-0.96) and had less improvement in depression severity (regression coefficient 1.06, P<0.0001).
Patients age 70 and older had the “worst outcomes” over 2 years, Schaakxs’ group said, compared to patients age 18 to 29 years old:
- MDD diagnosis: 45% versus 35%, OR 2.02 (95% CI 1.18-3.45)
- Chronic symptoms: 41% versus 18%, OR 3.19 (95% CI 1.74-5.84)
- Time to remission: 6.26 versus 19.31 per 100 person-months, HR 0.60 (95% CI 0.44-0.83)
- Mean depression severity change: -5.57 versus -12.64 points on the 30-item Inventory of Depressive Symptoms-Self Report scale
Even after adjustment for other factors, including loneliness, social support, pain, number of chronic disease, and BMI, the associations remained significant across the variables, except for likelihood of MDD diagnosis.
“The more unfavourable course of MDD towards old age was only explained to a small extent by clinical, social, and health factors that are common in old age and that are thought to worsen the course of the disease,” the group wrote, adding that loneliness was the only social factor that increased with age in patients with depression.
Treatment differences may also be an underlying factor in these differences, they suggested, noting that psychotherapeutic treatments are less commonly provided in older age. Although the older age groups in this study were more likely to use antidepressants — 73% of the 70 and older age group versus 33% of those 18 to 29 — the authors highlighted “it has been suggested that the effectiveness of antidepressants in older ages can be impaired because of medical comorbidity, frailty, and drug-drug interactions.”
The study included data on 1,042 individuals from the longitudinal Netherlands Study of Depression and Anxiety (comprising people 18 to 65 years of age) and the Netherlands Study of Depression in Older Persons (individuals 60 to 93 years old). Notably, the latter excluded patients with suspected dementia and a low score on the Mini-Mental State Examination (MMSE), which dropped the age range to 88.
All participants had a diagnosis of MDD within 6 months prior to enrollment and had a self-reported Inventory of Depressive Symptomatology score of at least 14 of 84 at baseline. Patients underwent in-person reassessment 2 years later.
To be more sure that dementia was not a confounder in their analyses, Schaakxs and colleagues performed a sensitivity analysis excluding all individuals who scored less than 25 points on the MMSE. Their main findings stayed robust.
Even so, the researchers acknowledged that they “cannot rule out that the presence of early phase dementia in the oldest age group might have contributed to our findings. It is paramount to assess the role of cognitive impairment in subsequent studies attempting to unravel age differences in the course of MDD.”
In an accompanying commentary, Tze Pin Ng, MBBS, PhD, of the Yong Loo Lin School of Medicine at the National University of Singapore, agreed that the exclusion “was insufficient to exclude a substantial contribution of variations in cognitive impairment to the observed differences in major depressive disorder trajectory,” adding that cognitive impairment is probably a major prognostic factor contributing to a worse trajectory of MDD in this older population.
Ng suggested these findings could also potentially be due to underlying metabolic and vascular factors in the older population, such as metabolic syndrome, chronic inflammation, and cerebrovascular disease.
“Further research should reveal more options for targeted treatment alternatives with insulin sensitizers, such as pioglitazone [Actos], for the treatment of MDD (and cognitive impairments) with a metabolic subtype in older patients,” he suggested.
The study was funded by the Netherlands Organisation for Health Research and Development, Fonds NutsOhra, Stichting tot Steun VCVGZ, NARSAD the Brain and Behaviour Research Fund, and the European Union’s 7th Framework Programme.
Schaakxs reported no relationships with industry. One co-author reported research funding from Janssen Research and Boehringer Ingelheim, unrelated to the current study. No other authors reported any disclosures.
LAST UPDATED
Primary Source
The Lancet Psychiatry
Secondary Source
The Lancet Psychiatry
#ASCO18: 3 unanswered questions
Each year, the ASCO annual meeting serves as a forum for some of the most important clinical studies in oncology, giving physicians important insights into how best to treat patients with cancer.
But the results are not always clear cut, particularly in the rapidly advancing field of immunotherapy.
Below are three pressing questions researchers are still grappling to answer:
Are Keytruda and Opdivo really all that different?
In April, a top executive from Bristol-Myers Squibb made headlines by claiming the pharma’s immunotherapy Opdivo (nivolumab) and Merck & Co. ‘s rival Keytruda (pembrolizumab) were more similar than different — a pharmaceutical version of Coke and Pepsi, in his words.Both drugs inhibit a checkpoint molecule known as PD-1. Both have also won a long list of approvals from the Food and Drug Administration to treat many of the same advanced cancers.Yet the remarks seemed to ignore the divergent paths taken by the two drugs in lung cancer.Opdivo, which still earns more than Keytruda, famously failed a large study testing the drug as a first-line treatment of non-small cell lung cancer. That left the door open for Merck, which has now won two approvals in the lucrative market.At this year’s ASCO, Merck presented data from a study roughly analogous to Bristol-Myers’ failed attempt two years ago: pitting Keytruda against chemotherapy in a broad range of NSCLC patients whose tumors expressed PD-L1 levels greater than 1%.Unlike Opdivo, however, Keytruda succeeded. Merck’s drug cut the risk of death in the overall study population by 19%. While high PD-L1 patients benefited the most, the result begs the question of why the two drugs performed so differently.Leena Gandhi, director of Thoracic Medical Oncology at the New York University School of Medicine, believes the trials are actually more similar than different, chalking up the split outcomes to study design.“Overall survival, although it was seen to be significant in [Merck’s] Keynote-042 study and not in [Bristol-Myers’] CheckMate-026 study, I think is in part explained by the differences in crossover,” Gandhi said, referring to protocols that let patients who fail chemo go on to receive immunotherapy while on study.More than 60% of patients in the chemo arm of CheckMate-026 received subsequent treatment with Opdivo, compared to only 20% in the chemo group of Keynote-042 who later received immunotherapy.“I think the drugs are very similar. I think it is study design and patient selection which has led to the differences,” said Jill O’Donnell Tormey, head of the Cancer Research Institute.Whether that’s true or not is still an open question. Either way, however, Bristol-Myers faces the uphill battle of unseating Merck in a market in which Keytruda now enjoys a commanding position.Which first-line immunotherapy regimen should lung cancer patients receive?
Entering ASCO, oncologists had evidence Keytruda helped certain patients with metastatic NSCLC live longer.But questions remained around which patients were best served by Keytruda alone and which would see greater benefit from receiving Keytruda together with chemotherapy.Results from two Phase 3 studies of Keytruda presented at this year’s conference help paint a clearer picture, highlighting the mainstay role Keytruda looks set to play in initial treatment of the disease.Currently, Keytruda is the only immunotherapy approved for first-line treatment of NSCLC. The PD-1 inhibitor is indicated as a monotherapy for patients with greater than 50% expression of the PD-L1 protein and in combination with chemo for all patients with nonsquamous NSCLC.New data showed pairing Keytruda together with a different chemo regimen also extended survival in patients with the harder-to-treat squamous form of NSCLC, regardless of PD-L1 expression. This suggested that, for all NSCLC patients without a driver mutation like EGFR or ALK, Keytruda plus chemotherapy is a superior option than chemo alone.A second study, testing Keytruda against chemo in NSCLC patients with greater than 1% PD-L1 expression, also attracted much attention at the conference. Results from the trial found Keytruda monotherapy reduced the risk of dying versus chemo in that broadly selected patient population.Much of the survival benefit seen, however, was due to responses among patients with high PD-L1 levels.“This benefit is clearly being driven by the higher PD-L1 subgroup,” remarked NYU’s Gandhi. “The benefit is not at all as clear cut for those with 1% to 49%, where a much larger percentage of patients are not benefiting from immunotherapy.”Keytruda alone, however, was much less toxic than chemotherapy, suggesting that it could play a role for patients who aren’t good candidates for chemo.Gilberto Lopes, who led the second Keytruda study, said in an interview the medical consensus will likely coalesce around giving immunotherapy together with chemo for patients who express between 1% and 49% PD-L1, while opting for Keytruda by itself in PD-L1 high individuals.That approach could be complicated, however, by ongoing studies conducted by Merck’s rivals Roche and Bristol-Myers of their own checkpoint inhibitors.Bristol-Myers, in particular, is developing a combination of two immunotherapies, Opdivo and Yervoy, which could offer a chemo-free option for patients who express a different biomarker known as tumor mutation burden.What is clear, however, is the role immunotherapy now plays in first-line lung cancer treatment.“Chemotherapy alone is no longer a first-line standard of care in non-small cell lung cancer,” said Gandhi in remarks at a plenary session.Have companies moved too fast to advance immunotherapy combinations into large trials?
Pairing immunotherapies with other drugs has been a central focus of the industry’s recent investment in cancer R&D. More than 1,100 ongoing combination studies involving the five approved checkpoint inhibitors are now underway.So far, all of that research activity has yielded few clear-cut successes outside of immunotherapy and chemo pairings.Earlier this year, for example, a closely watched Phase 3 study of Incyte’s IDO inhibitor epacadostat and Keytruda in melanoma failed — showing Incyte’s drug added no benefit whatsoever. It was a crushing blow to one of the industry’s most advanced combinations and sparked questions of whether the two drugmakers moved too quickly.Investors now appear worried that another high-profile combination could follow the same pattern. On Monday, Nektar Therapeutics lost $6 billion from its market capitalization as investors digested a confusing update on the biotech’s combination of its experimental drug NKTR-214 with Opdivo.Encouraged by promising data among just several dozen patients, the partners greenlighted three late-stages studies of the two drugs in melanoma, kidney and bladder cancers.The decision raised doubts of whether the companies had enough data to merit advancing into Phase 3, particularly as a second group of patients didn’t appear to experience the same high level of responses.It’s a question that faces the entire field, as companies are forced to weigh waiting for more (or any) randomized data against advancing quickly with pairings that present a strong biologic rationale for combining.“Is there enough of the translational data [generated]? Or are we going down another pathway of what happened with IDO — jumping from early to now spending millions on many patients,” said CRI’s O’Donnell-Tormey.At the same time, others argue that when there is enough evidence to suggest strong potential, it’s worth investing in.“It is really easy to say every asset needs a randomized Phase 2 before moving into Phase 3,” explained Kim Blackwell, head of early-phase oncology development at Eli Lilly, in an interview.“But there is also a time [element] here — if you have good science and you have a safe agent in the early phase, sometimes going directly to a large clinical trial might get you there faster. Our patients need better therapies.”
How Fujifilm became a contract manufacturer
Some might believe Fujifilm and Mitsubishi would make strange bedfellows, but a joint venture between the pair has resulted in the contract development and manufacturing organization Fujifilm Diosynth Biotechnologies. The parent company has said it aims to hit $1 billion in worldwide sales for its bio CDMO division by 2024.
BioPharam Dive sat down with Steve Bagshaw, CEO of the joint venture, to talk about their customer base, the move to gene therapies and how the industry is evolving.
BIOPHARMA DIVE: Why Fujifilm?
STEVE BAGSHAW: That might be the first question anyone ever says, “Why Fujifilm?” We’ve been part of Fujifilm now for seven years and very much part of their healthcare commitment. They wanted to leave the traditional fields of film and document solutions and move into something that would have a longevity — something they could bring that technology into, but wasn’t necessarily doing what they used to do.
They’re working with us in biotech manufacturing in a way that we have never really got to the levels they’ve got us to in terms of being able to get manufacturing quality right the first time using some of the technology development that Fuji has in their heads. For us it was an unusual combination because we had the same reaction when they were buying us, “Well, why are you buying?” But it’s become more and more obvious as we’ve been doing it that these guys have a depth in this area that is really helping us.
What do you bring to the table?
BAGSHAW: We’re the people who are just basically making sure that there’s a whole supply chain of big pharma, medium pharma, biotechs, mobile techs, all wanting to work with us. Then we’ve created a road map of services that we can provide to the market and in the last seven or eight years we’ve spent maybe $250 million investing in assets. We’re now 1,200 people strong in three locations in Texas, North Carolina, and Billingham in the northeast of England.
Steve Bagshaw
Credit: FujiFilm Diosynth Biotechnologies
In those three locations we offer a service to the market of development, analytical sciences, analytical services formulation and then in certain fields we’re also doing drug products manufacture, in terms of making the final dose for the project. But typically we stop at the end of making the drug substance, and then another expertise is to actually put that in the vial or the syringe or whatever the package that they think the market can use.
We have this business really that’s a really nice combination. We’re a joint venture in Fujifilm and Mitsubishi. We don’t publicize too much the Mitsubishi piece. It’s an 80/20 [split] but Mitsubishi are long-term trading partners of the world and so we use that expertise in terms of partnership and we use the Fuji expertise in manufacture and technology development. That’s where we come from.
The biotech world has changed dramatically in the last five to seven years, particularly on the manufacturing side with the advent of new technologies. How has the company evolved with that?
BAGSHAW: We’ve really invested heavily in single-use bioreactors and mobile clean rooms. Creating clean room spaces that are very reconfigurable for small quantities and using single-use bioreactors because we find that we spend a lot of time just cleaning your facilities because we’re very multi-product. If you have a big quantity of something to make, you’ve got a choice really whether you would make it yourself or get a CMO to make it.
Typically, we’ll have 70 different clients that we’re partnering with at any one time all going towards manufacture in our three facilities. We can reconfigure the plan to do any process they want. To us, that’s really helping them because not everybody wants the same process.
We’re also developing platforms so where there is a platform opportunity we’ll do it, but actually our history and where we came from is, “You want this. She wants that. He wants that. They’re three different requests we’ll make it for you flexibly.”
And that’s differentiated us actually from the competition, because the competition were very much about going, “It’s our way or the highway.” We came in and said, “Well, we’re the new kids on the block,” and we couldn’t win by being, “It’s our way or the highway.” We had to develop flexibility, and that’s what we’ve done and we’ve made it a strength.
Hence, now we see the good we’ve done now. We’re growing faster than we’ve ever grown before. We had another record year last year in terms of sales and profit and then continuing to grow like that and Fuji investing in us year on year to do that.
Tell me about your client base. Are they in a particular phase? Of a certain sized company? Certain therapeutic areas?
BAGSHAW: Phase-wise, we’ve got many preclinical and Phase 1 customers. We’re playing in that front end very much. Often we’ll make a batch for somebody and we’ll never see them again at that company. What we find is the guy or the gal that brought it to us will come with their next company in five years time going, “Hey, I’m back.”
It’s like old friends coming back bringing their new company to see us because five years ago we did this great project for them, made something, and now they’re coming for new technology. People are bringing us microbiome projects or they’re bringing us gene therapy projects. Some of them are the same people that brought us cell culture products five, 10, 15 years ago.
We’ve got three, four or five big pharma collaborations where there’s a — I don’t know what they’ll ask us tomorrow to do, but because we’ve been willing in the past to listen to them and say, “We’ve never done that before but we’ll do it with you,” that’s taking us places we’ve never been. It’s great.
Gene therapy is one of these areas where they’re going, “We know that if we grow this business, we don’t know how to make it. We’ll partner with you because you’re dealing with all these people, all these small guys. You’re gaining a technology sense of what’s possible and we want to work with you going forward,” and that’s fantastic that people are trusting us to be the leaders in gene therapy.
How have you handled some of the hurdles of gene therapy? Transport hurdles, turn around time on things like this, manufacturing consistency with the product?
BAGSHAW: We’ve had to recruit people who know what they’re doing. We brought some great players, but our track record is growing because we brought the same approaches that we have to cell culture and fermentation. We’ve brought that to the repeatable mentality and to doing process development in our laboratories, in Texas particularly, and using that same methodology to create processes that are repeatable.
We’re all wrestling with the same thing, which is how do you do the scale up? How do you do regulatory scale up, because it’s quite different biology really, so how do you do that? We’re playing in that field, very much partnering and getting involved. We don’t have the answers, but we know we’ve got a track record to help us in that area so that’s what we’re doing.
There’s been a lot of consolidation across your field. How has that impacted you? Is that bringing in more business or creating more competition to get clients?
BAGSHAW: A bit of both actually. Consolidation where it means someone wants to close a site is always a problem. If it’s consolidation where they’re just changing the name on the front door, not much business comes out of that. What’s interesting, I think, is everyone recognizing that you’ve got to be a long-term player.
I think the whole CDMO industry has gained reputation there actually, and we’ve all benefited from all playing a longer-term game, because we’re all long-term partners now.
The Importance of Having One Big Thing to Work On
I’ve read hundreds if not thousands of journal entries during my years of working with traders. One pattern shows up among the traders who make greater success:
Their performance journals are highly focused.
The trader surveys his or her trading and identifies one big thing to work on that will make the greatest difference to the bottom line. They sustain that single focus until they have demonstrated significant progress. Then they move to another “big thing” goal to work on.
The lesser successful traders recount everything that has happened in their trading and what they need to do better next time. Lots of good intentions, not many concrete goals.
It is difficult to sustain a sense of urgency when working on many things at one time. When there are many goals, it’s easy for a priority at one time to distract from efforts at other priorities.
When I see the progress of traders with many goals, it is difficult to pinpoint where they have made dramatic improvements. The more successful traders seem to be working on fewer things but they actually get more accomplished.
Here’s the framework I’m using for my own trading: one prioritized goal per month. Each day I have a specific plan for working on that goal and each day I review my recent work on the goal and modify my plan. If there are roughly 20 trading days in the month, that means that I have at least 20 reps in my workout, 20 trials in my deliberate practice. The reality is that I have more than that, because I take midday breaks in my trading and treat morning and afternoon as separate trading “days”. So that means 40 reps, working on just that one goal.
Then a new goal the next month.
And the next month.
By the end of the year, the idea is to have 12 big things that you’ve accomplished, each making you better. That’s a big outcome, and it springs from a small beginning: a single important thing to work on that will make a positive difference in your trading. Keeping a report card on your trading is huge. Focusing that report card takes it to the next level.
What’s your One Big Thing?
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