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Monday, February 10, 2020

GenMark Diagnostics CEO Massarany to depart in shakeup

GenMark Diagnostics (NASDAQ:GNMK) says Hany Massarany has stepped down as President and CEO and as a board member, effective immediately.
GenMark appoints COO Scott Mendel as interim President and CEO.
The company also names Kevin O’Boyle as Chairman, while prior chair James Fox will remain on the board as a non-executive director.
Massarany was President and CEO since 2011 after holding various positions with Ventana, Roche Diagnostics, Bayer Diagnostics and Chiron Diagnostics.
Mendel has served as COO since last February after joining GenMark as CFO in 2014.
https://seekingalpha.com/news/3540329-genmark-diagnostics-ceo-massarany-to-depart-in-shakeup

Regeneron builds preventive case for Eylea with new 2-year data

Despite facing a highly touted competitor in Novartis’ Beovu, Regeneron hasn’t broken a sweat as blockbuster eye med Eylea continues to gobble up market share. Already in the lead in multiple indications, new two-year data could help Regeneron make the case for its drug in the preventive setting as well.
After two years, injectable Eylea sliced the risk of vision-threatening complications by 75% over placebo in patients with non-proliferative diabetic retinopathy, according to phase 3 data released Friday.
Regeneron touted the data as a case for physicians to use Eylea preventively, as 58% of patients in the phase 3 Panorama trial’s control arm developed diabetic macular edema or compromised vision at the two-year mark.
The FDA approved Eylea in May to treat all stages of diabetic retinopathy, a condition that affects about 8 million people worldwide and is the leading cause of blindness in U.S. adults, the company said.
The administration based its nod on six- and 12-month data from the Panorama study showing Eylea significantly cut the risk of patients developing proliferative diabetic retinopathy when treated every eight and 16 weeks.

Eylea’s newest data will likely give Regeneron even more confidence that its blockbuster can weather the storm as competitors like Novartis’ Beovu take on the stalwart in wet age-related macular degeneration (AMD).
In the fourth quarter, U.S. sales of Eylea jumped 13% year over year to $1.22 billion, slightly ahead of industry watchers’ expectations of $1.20 billion. Regeneron commercial chief Marion McCourt tied Regeneron’s booming success to its sustained market dominance in AMD as well as its growing penetration in diabetic eye disease. The drugmaker also rolled out a prefilled syringe application in December that McCourt said would drive volume in the future.
Also on Friday, Regeneron announced it would enroll patients in a phase 2 study of high-dose Eylea in wet AMD, potentially setting the stage for a future regulatory filing.
Those figures are good news for Eylea as Beovu, just months into its launch, hit $35 million in sales in its first quarter and has attracted some positive reviews from physicians.

In an earnings call earlier this month, Novartis said Beovu had received “outstanding feedback” so far, with 84% of retina specialists actively prescribing the drug. Evercore ISI analysts said at least one physician saw a “dramatic improvement” in patients treated with Beovu over both Eylea and a third competitor, Roche’s Lucentis.
Those positive reviews spelled dollar signs for Evecore, which said that Beovu could be well on its way to capturing half of the AMD market within the next two years.
It’s not all sunshine and roses for Beovu, though: After its approval in October, Piper Jaffray analyst Christopher Raymond called the drug’s label a “hot mess” without any Eylea-topping data included and no four-week dosing schedule. SVB Leerink analyst Geoffrey Porges had choice words of his own, blasting the Beovu label’s “lack of clarity” on dosing, including sparse language directing physicians on how to choose between eight- and 12-week schedules.
https://www.fiercepharma.com/pharma/regeneron-builds-preventative-case-for-eylea-new-2-year-data

Telepsychiatry Filling a Critical Gap in US Emergency Care

A national shortage of psychiatric services means a growing number of US emergency departments (ED) are turning to telepsychiatry to fill a critical treatment gap, new national data show.
Investigators surveyed over 5300 EDs and found that 20% of those that responded to the survey were utilizing telepsychiatry services, especially in high-volume EDs, those located in rural areas, and those designated as critical access hospitals.
A second survey of 95 EDs conducted by the same group found that for the majority, telepsychiatry was the only form of emergency psychiatry services, with one quarter receiving such services at least once a day — especially in admission or discharge decisions and transfer coordination.
The findings “suggest that telepsychiatry fills a critical role by enabling many EDs to access emergency psychiatric services,” study investigators Rain Freeman, MPH, and Carlos Camargo, MD, DrPH, told Medscape Medical News via email.
Freeman is an epidemiology specialist at the University of Montana’s School of Public and Community Health Sciences in Missoula, and Camargo is founder and division chief of the Emergency Network Coordinating Center at Massachusetts General Hospital in Boston.
The study by Freeman, Camargo, and colleagues was published online February 5 in Psychiatric Services.

Dearth of Psychiatric Services

“In recent decades, psychiatric services have become increasingly difficult to access because of a shortage of mental health professionals and a decrease in dedicated beds,” the study authors write.
Due to cuts in hospital and community psychiatric services, many patients  experiencing mental health crises have no choice but to attend the ED for care, resulting in growing numbers of ED psychiatric visits and boarding of psychiatric patients awaiting bed placement.
Telepsychiatry is emerging as a way of helping to mitigate the “dearth of psychiatric services available” in the ED, write the authors. Telepsychiatry allows psychiatrists to evaluate patients remotely, “thus making psychiatric services more accessible, even to patients located in rural, underserved areas.”
“We wanted to know what ED telepsychiatry use looks like across the country [because], while research exists on telepsychiatry effectiveness and outcomes for specific programs, there is limited information on national trends,” Freeman and Camargo said.
“Through two nationally representative surveys, we aimed to find out how many EDs receive telepsychiatry and what they use it for,” they said.
The first survey examined ED care provided in 2016 by 5375 EDs that were open 24/7, 365 days a year, identified through the National Emergency Department Inventory (NEDI)-USA database, to determine annual visit volume, presence of a pediatric emergency care coordinator, and aspects of telemedicine use.
The second survey randomly sampled 130 of the 885 EDs that reported utilizing telepsychiatry services in 2016.

Earlier Intervention

Of the EDs initially contacted, 84% (4507) responded to the survey; of the 4410 responders that completed the telepsychiatry question, 20% (885) reported using telepsychiatry.
Unadjusted analyses showed these EDs were more often hospital-based and satellite freestanding EDs (FSEDs) and less frequently autonomous. EDs were also more likely to receive telepsychiatry if they were rural and if they had a critical access hospital designation.
Multivariable analysis showed several differentiating characteristics of EDs that used telepsychiatry vs those that did not.
  • Annual total ED visit volume ≥ 10,000
  • Presence of a pediatric emergency care coordinator
  • Satellite rather than hospital-based FSED
  • South rather than Northeast region
  • Rural location
  • Critical access hospital designation
EDs that were less likely to receive telepsychiatry services had a larger annual total visit volume by children, were autonomous FSEDs, and were located in a geographic mental health professional shortage area (HPSA).
Of the 130 EDs that reported in the initial survey using telepsychiatry services, 81% (105) responded to the second survey, with over 90% confirming their earlier report of receiving telepsychiatry.
Over half (59% [95% CI 49% – 69%]) reported that telepsychiatry was the only type of emergency psychiatric service available.
Telepsychiatry was most commonly used in admission or discharge decision-making (80%), followed by transfer coordination (76%), diagnosis (56%), and treatment (45%).
“The telepsychiatry provider may interact with the patient for diagnostic evaluation or treatment, or they may only act as consultants to the ED staff for a variety of needs related to ED mental health care,” said Freeman and Camargo.
Using telepsychiatry in diagnosis and treatment may facilitate earlier delivery of care, they suggest.

Improving Access

The researchers queried respondents about average wait times between an admission request and actual admission to a psychiatric unit.
  • Adult patients:
  • Average wait time 6 – 11.9 hours: 24% of EDs
  • Average wait time ≥ 12 hours: 47% of EDs; roughly half of these reported telepsychiatry as the only form of psychiatric service
  • Maximum wait time of > 1 day: 68% of EDs, with wait times ranging from just over 1 day to 30 days
  • Pediatric patients:
  • Average wait time 6 – 11.9 hours:  29% of EDs
  • Average wait time ≥ 12 hours: 40% of EDs; half of these reported telepsychiatry as the only form of psychiatric service
  • Maximum wait time of ≤ 1day: > 50% of EDs
  • Maximum wait times of > 1 day: 42% of EDs, with wait times ranging from just over 1 day to 90 days
“In many EDs, there is a limited delivery of mental health care during the boarding process,” with “extended” waits for placement and receiving care, the authors note.
Telepsychiatry can assist with inpatient placement, potentially alleviating ED crowding in several different ways, such as helping ED physicians understand the difference between emergent and nonemergent psychiatric cases or securing the inpatient psychiatric beds more effectively, they add.
The investigators also note that telepsychiatry may be effective “for creating accessible services and streamlining the ED process, with favorable effects on ED boarding and crowding and better utilization of limited resources.”

Obvious Benefits

Commenting on the study for Medscape Medical News, Michael Wilson, MD, PhD, assistant professor, Department of Emergency Medicine, University of Arkansas for Medical Sciences, Little Rock, said the study is “the first and certainly most comprehensive survey of ED use of telepsychiatry.”
The benefits of telepsychiatry are “pretty obvious” because “we’re pretty sure that having someone specialized in mental health care to evaluate these patients is better than having someone not specialized in mental health care,” said Wilson, who is also the director of the Department of Emergency Medicine Behavioral Emergencies Research lab and was not involved with the study.
“The more expert the person doing the evaluation is, the better the results, which isn’t surprising,” he noted.
An additional benefit of telepsychiatry is that the average ED physician does not necessarily have time to conduct a full evaluation, so involvement of a psychiatrist via telepsychiatry is especially important, he said.
He noted that a problem with telepsychiatry is that “we don’t know how this will play out with regulation and licensing, creating a lot of confusion, since out-of-state providers may need special credentialing” and telepsychiatrists seeking to expand into multiple states and provide services “may need credentialing in multiple places, so the amount of paperwork can be staggering.”
Moreover, “the DEA [US Drug Enforcement Administration] has not yet publicized final regulations about offering some kind of substance abuse treatment, such as buprenorphine, via telepsychiatry,” Wilson said. “So although we have evidence that buprenorphine works, how that can be prescribed has not yet been fully worked out.”
This study was supported by a grant from the Emergency Medicine Foundation and the R Baby Foundation. The authors have disclosed no relevant financial relationships. Wilson reports serving on the editorial board of the Journal of Emergency Medicine.
Psychiatric Services. Published online February 5, 2020. Abstract
https://www.medscape.com/viewarticle/924993#vp_1

Another Alzheimer’s failure for Biogen bulls to shrug off

Wonder whether Biogen’s resurrection of aducanumab has stoked unrealistic hopes for Alzheimer’s disease progress? Look no further than Lilly’s shares, which opened 4% down this morning on the failure of the Dian-Tu study, an ambitious trial handicapped by a very small sample size.
Biogen shares were largely unmoved, meanwhile; while a positive signal in Dian-Tu would have been claimed as a major endorsement of the beta-amyloid hypothesis, aducanumab bulls have swiftly pointed to trial design and differences in the antibodies involved. These might be valid points, but yet another setback for this space only emphasises just how precarious Biogen’s position is here.
Dian-Tu was run by Washington University, and tested two failed anti-amyloid beta antibodies, Lilly’s solanezumab and Roche’s gantenerumab, in subjects with a rare inherited form of early-onset dementia called autosomal-dominant Alzheimer’s disease (ADAD). Because these individuals display degeneration at a predictable age, researchers hoped to tease out a benefit in a small number of subjects (Another chance for Lilly and Roche to take on Alzheimer’s, January 31, 2020).
None was seen, at least according to the primary endpoint of the study: neither project showed a significant slowing of cognitive decline, statements from Lilly and Roche said today. These press releases also confirmed the very small number of patients that received the active agents; 52 were randomised to receive gantenerumab, while only 50 received solanezumab.
The full data, due to be presented at a medical conference in April, remain of interest. The high doses tested in Dian-Tu helped rekindle hopes here, echoing Biogen’s case for finding a way forward for aducanumab: that if you dose patients high enough and long enough, an effect can be seen. But Dian-Tu only hiked the dosages half way through; this, and the very small sample size, will surely render any positive signals to emerge in the full results exploratory at best.
Important differences? How the amyloid-beta antibodies differ, mechanistically

Aducanumab  Gantenerumab  Solanezumab
Target Fibrillar and oligomeric amyloid-beta Fibrillar and oligomeric amyloid-beta Soluble monomeric amyloid-beta
Epitope N-terminus (3-7) N-terminus (3-11) and mid-domain (18-27) Mid-domain (16-26)
Plaque binding  Yes Yes No
Source: sellside research.
Analysts at SVB Leerink, who only a few weeks ago declared that the Dian-Tu outcome would influence whether confidence in beta-amyloid as a target, and thus Biogen’s antibodies, went up or down, today decided that the outcome had limited impact on aducanumab. The bank has been a major supporter of Biogen’s stance that aducanumab is approvable.
These three anti-beta-amyloid antibodies all work slightly differently, targeting different epitopes, Leerink pointed out. Again, the small number of patients involved here surely means that mechanistic conclusions are hard to draw.
Still, it is hard to escape the notion that Biogen’s putative progress with aducanumab raised unrealistic hopes here. The next big test for this mechanism will probably come from Roche’s gantenerumab, which is due to complete a prodromal study later this year, and Biogen bulls will no doubt be ready with reasons should this fail too.
Selected upcoming Alzheimer’s disease readouts
Company  Project Mechanism Trial Setting Estimated timing
Roche gantenerumab Anti-beta-amyloid MAb NCT01224106 Prodromal (phase III) Mid-2020
Roche/AC Immune Semorinemab (RG-6100) Anti-Tau MAb NCT03289143 Prodromal/Mild AD ( phase II) Mid-2020
Biohaven troriluzole Glutamate modulator NCT03605667 Mild-to-moderate AD (phase II/III Late 2020
Eli Lilly Donanemab (LY3002813) N3PG antibody Trailblazer-Alz NCT03367403 Early symptomatic AD (phase II) Late 2020
Cortexyme COR388 Gingipain inhibitor Gain NCT03823404 Mild to moderate AD (phase II/III) Poss interim analysis mid/late 2020; completion late 2021.
Abbvie ABBV-8E12 Anti-Tau MAb NCT02880956 Early AD (phase II) 2020 (primary completion Apr 2021)
Roche gantenerumab Anti-beta-amyloid MAb NCT02051608 Mild AD (phase III) Q2 2021
Biogen Gosuranemab (BIIB-092) Anti-Tau MAb Tango NCT03352557 Early AD (phase II) 2021
Lilly Zagotenemab (LY3303560) Anti-Tau MAb NCT03518073 Early symptomatic AD (phase II) 2021
Source: EvaluatePharma & company statements.
https://www.evaluate.com/vantage/articles/news/trial-results/another-alzheimers-failure-biogen-bulls-shrug

J&J files U.S. application for expanded use of Darzalex

Johnson & Johnson (NYSE:JNJ) unit Janssen Pharmaceutical Companies has filed a supplemental marketing application with the FDA seeking approval to use Darzalex (daratumumab), combined with Amgen’s (NASDAQ:AMGN) Kyprolis (carfilzomib) and dexamethasone, to treat patients with relapsed/refractory multiple myeloma (MM).
The agency first approved the CD38-directed cytolytic antibody in November 2015 for previously treated MM. It subsequently approved five additional uses (mostly combinations) in MM.
https://seekingalpha.com/news/3540289-j-and-j-files-u-s-application-for-expanded-use-of-darzalex

Merck passes on KalVista DME candidate

KalVista Pharmaceuticals (NASDAQ:KALV) announces that its option agreement with Merck (NYSE:MRK) related to KVD001, its candidate for the potential treatment of diabetic macular edema (DME), and future oral DME molecules has expired.
Merck had the option to in-license KVD001 and future oral plasma kallikrein inhibitor programs for DME via paying a non-refundable $37M fee to KalVista who now has no obligations to Merck and retains full ownership of all assets.
https://seekingalpha.com/news/3540308-merck-passes-on-kalvista-dme-candidate

LogicBio -26% as FDA puts hold on LB-001

LogicBio Therapeutics (NASDAQ:LOGC) has slid 26.3% postmarket after the company announced the FDA has placed a clinical hold on its LB-001, for the treatment of methylmalonic acidemia.
That hold is pending the resolution of clinical and nonclinical questions, the company says. It expects hte questions will be provided in writing within 30 days.
The company submitted an Investigational New Drug application in January with an eye toward a Phase 1/2 clinical trial.
https://seekingalpha.com/news/3540327-logicbiominus-26-fda-puts-hold-on-lbminus-001