U.S. CDC recommends schools reopen with masks and rigid health protocol

 The U.S. Centers for Disease Control and Prevention on Friday issued new guidance for U.S. schools to reopen, recommending universal mask-wearing and physical distancing as key COVID-19 mitigation strategies to get children back in the classroom quickly.

FILE PHOTO: English Language Program teacher Marlon Henriquez and bilingual teacher at Pilsen Community Academy Daniela Lugo prepare for a car caravan of supporters of the Chicago Teachers Union, as negotiations with Chicago Public Schools continue over a coronavirus disease (COVID-19) safety plan agreement in Chicago, Illinois, U.S., January 30, 2021. REUTERS/Eileen T. Meslar/File Photo/File Photo

The guidelines here, which also emphasize the need for facility-cleaning, personal hygiene and contact tracing, are intended to give school districts a road map to bring the nation's 55 million public school students back to classrooms without sparking COVID-19 outbreaks.

“We believe with the strategies we have put forward that there will be limited to no transmission in schools if followed,” CDC Director Rochelle Walensky told reporters, noting that the CDC was not mandating that schools reopen.

The agency also said school reopenings should not be conditional on teachers’ access to COVID-19 vaccines, but strongly recommended U.S. states prioritize teachers and school staff for vaccination.

President Joe Biden promised to reopen most K-8 schools within 100 days of taking office on Jan. 20. He praised the CDC’s guidance on Friday and emphasized the problems arising from the continued closure of schools, including children’s mental health struggles and the exodus of parents from the workforce.

“We have sacrificed so much in the last year. But science tells us that if we support our children, educators, and communities with the resources they need, we can get kids back to school safely in more parts of the country sooner,” Biden said in a statement.

Just 44% of U.S. school districts were offering fully in-person learning as of December and 31% were operating all remotely, according to the Center for Reinventing Public Education, which surveyed 477 of the nation’s nearly 13,000 school districts. Other districts have employed a hybrid learning model, where students attend some school days in-person and some virtually.

School reopenings have caused labor disputes between teachers unions, who fear for their members’ safety, and school districts in major U.S. cities. In Chicago this week, the teachers union and district reached agreement on a safety plan after months of negotiations that included threats of a strike.

On Friday, the American Federation of Teachers, which has about 1.7 million members, commended the CDC’s guidance for relying on “facts and evidence.”

“We urge the CDC to remain flexible as more data comes to light. The guidance is instructive for this moment in time, but this disease is not static,” AFT President Randi Weingarten said in a statement.

FLEXIBLE APPROACH

The CDC’s phased mitigation strategy is adaptable depending on the level of COVID-19 transmission in a school’s community.

In areas where the COVID-19 positive test rate is below 5% and there were fewer than nine new cases per 100,000 in the last seven days, schools can fully reopen and safely relax social distancing measures as long as masks are worn, Walensky said. In areas of higher transmission, the agency is urging 6 feet (1.83 m) of separation in classrooms and weekly testing of students, teachers and staff.

Elementary school students should learn in-person at least part-time even in areas of high transmission, the guidance says.

Recent studies have shown that in-person learning has not been associated with increased community transmission, especially in elementary schools.

House Republican Leader Kevin McCarthy criticized the reopening guidelines on Friday as not bold enough to ensure that students return to classrooms promptly.

“Families and students deserve better. They need iron-clad assurances that their children will be able to get back into the classroom environment that offers the best education model,” McCarthy said in a statement.

U.S. House Speaker Nancy Pelosi, a Democrat, said on Friday that House committees were working to pass Biden’s $1.9 trillion American Rescue Plan legislation, which includes a $130 billion investment that could help schools follow the CDC protocols, to help schools enforce the CDC’s guidelines.

“Without strong assistance from Congress, our schools cannot afford to enact the science-based safety precautions required,” Pelosi said in a statement.

https://www.reuters.com/article/us-health-coronavirus-usa-education/u-s-cdc-recommends-schools-reopen-with-masks-and-rigid-health-protocols-idUSKBN2AC171

Citigroup Downgrades Alnylam Pharmaceuticals to Neutral

 Ups  target to $175

https://www.benzinga.com/news/21/02/19639618/citigroup-downgrades-alnylam-pharmaceuticals-to-neutral-raises-price-target-to-175

Hyundai debuts device that can help paraplegics walk

 Like most automotive manufacturers at this year’s CES, Hyundai put an emphasis on its self-driving concept car. But the real innovation on display from the company had nothing to do with vehicles.

Off to the side of the crowded booth sat a spherical display featuring a trio of prototype exoskeletons Hyundai is hoping to get into the market soon. Each of the devices offered a different functionality — aiding in industrial work, helping to carry elderly people and giving paraplegics the chance to walk again.

Hyundai says it hopes to make the H-MEX more affordable than existing exoskeletons, since it has factories capable of mass-producing other sorts of mobility devices.

Photo: Morgan J Segal Photography | Hyundai

“A car is one kind of mobility device,” says Jung Kyungmo, senior research engineer on the Human Factors and Devices Research team at Hyundai. “Exoskeletons [are] another kind of mobility device we think, so we developed [this].”

Hyundai’s not the first to create an exoskeleton, of course, but it’s approaching the field much like it did with the auto industry: with an eye toward making them more accessible and affordable to a larger audience.

The mechanics

It’s likely going to be some time before they’re available commercially, however. Kyungmo says all of the devices that were being shown and demoed at CES were prototypes, and they’ve just started doing clinical trials with the goal of getting FDA certification in the United States (and the corresponding medical certification in Korea). At present, it doesn’t expect to achieve that goal before 2018. And even once that milestone is achieved, the product will face a slow consumer rollout.

The H-MEX (Hyundai Medical Exoskeleton), designed for paraplegics, was the first exoskeleton born from the company’s R&D labs. That device not only allows people paralyzed below the waist to take steps but also improves blood circulation among patients. Additionally, says Kyungmo, the exoskeleton can be used in rehabilitation for patients with spinal injuries that have not resulted in permanent paralysis.

To the outward observer, the H-MEX resembles old-style leg braces (think about what a young Forrest Gump wore in the 1994 Academy Award-winning film) with a bulky battery pack nestled in the small of the user’s back. Leg lengths on the exoskeleton are adjustable to fit any user.

The aluminum frame that straps to your feet, legs and back with hinges on the knee and waist has a backpack with a lithium battery that operates for up to four hours. Carbon fiber walking canes feature controls that move each leg forward, instruct the device to sit down, and tell it to climb stairs.

Hurdles lie ahead

They’re used in conjunction with crutches that feature controls that move each leg forward, instruct the device to sit down and tell it to climb stairs. Encouraged by H-MEX, the company then developed H-WEX (Hyundai Waist Exoskeleton), designed to make it easier for workers who work in factories.

“The robot gives them additional back support. ... It can help the worker ... to lift the heavy object,” says Kyungmo.

Following that was HUMA (Hyundai Universal Mobility Assist), which was designed to carry the elderly and could have potential military applications.

Beyond the FDA clearance, there are a few issues to note about H-MEX. It’s not for everyone. Users must be no shorter than 5 feet 4 inches tall, for example. The cost is still not announced.

Hyundai’s not alone in the exoskeleton world. Rex Bionics, based in London, also has a device for paraplegics, though that is not yet for sale in the United States, in part because it has not been registered with the FDA. Publicly traded ReWalk (RWLK) does sell exoskeletons domestically, however — and was the first company to receive FDA clearance to use them for personal and rehabilitative use in the United States. The company’s ReWalk Personal 6.0 has a list price of $77,000.

While Hyundai won’t even speculate on prices at this time, it says it hopes to make the H-MEX more affordable than existing exoskeletons, since it already has factories capable of mass-producing other sorts of mobility devices.

https://www.cnbc.com/2017/02/01/hyundai-debuts-a-miracle-device-that-can-help-paraplegics-walk.html

Jefferies Upgrades Prothena Corp to Buy

Target to $30

https://www.benzinga.com/news/21/02/19633183/jefferies-upgrades-prothena-corp-to-buy-raises-price-target-to-30

FDA grants Moderna permission to up doses in each vial from 10 to 14

 The Food and Drug Administration (FDA) granted Moderna permission to increase the number of COVID-19 vaccine doses per vial from 10 to 14, the New York Times reports. 

Moderna did not confirm the approval Friday but told Fox News it is currently in discussions with the FDA about a "potential increase in fill volumes, thus enabling extraction of additional doses from each vial delivered."

One of the biggest constraints to Moderna's manufacturing capacity is how many vials can be filled. 

"In order to better maximize resources as well as maximize opportunities to deliver more doses into each market faster, Moderna has proposed filling vials with up to 15 doses of vaccine versus the previous 10 doses," a Moderna spokesperson told Fox News Friday. 

The FDA said Friday it cannot comment on discussions it is having with a manufacturer. 

"Generally speaking, any changes to an [Emergency Use Authorization] must be requested by the company and include data supporting the requested change and would be authorized via a granting letter or reissuance of the letter of authorization, which would be posted on FDA’s web site," an FDA spokesperson told Fox News. 

Moderna currently provides roughly half of America's vaccine supply. Because the increased number of doses per vial would not require different vials than the ones currently being used, it would be a simple way to increase the number of doses available. The manufacturing change would take two to three months to implement. 

President Joe Biden said Thursday that the U.S. is on track to deliver more than 600 million doses of the COVID-19 vaccine between Modern and Pfizer by the end of July, enough to fully vaccinate almost every American. 

"Just this afternoon, we signed the final contracts for 100 million more Moderna and 100 million more Pfizer vaccines," Biden said Thursday at the National Institutes of Health. "We’re also able to move up the delivery dates with an additional 200 million vaccines to the end of July, faster than we expected."

The FDA is currently considering an emergency use authorization request by a third drug company, Johnson & Johnson, for its COVID-19 vaccine. 

Moderna is contracted to supply 300 million doses to the U.S. and another 341.5 million doses to countries around the world. 

So far, 69,014,725 doses have been distributed and 48,410,558 doses have been administered in the United States, according to the CDC. 

Moderna's scaled-up manufacturing capacity comes as COVID-19 variants continue to rapidly spread throughout the country. 

https://www.foxnews.com/health/fda-grants-moderna-to-increase-doses-vial

Asco-GU – confirmatory Seagen Padcev trial throws a curveball

 Seagen/Astellas’s bladder cancer drug Padcev is expected to be selling nearly $4bn in five years’ time, according to EvaluatePharma sellside consensus, but its confirmatory EV-301 study has thrown doctors a curveball.

The data, being presented today at the Asco-GU meeting, appear to show that the drug does not work in women. However, the companies can probably shrug off this post hoc subgroup analysis and, even if doctors now shy away from prescribing Padcev to female patients, women comprise a relatively minor portion of this cancer type.

Padcev, an anti-nectin-4 antibody-drug conjugate, received US accelerated approval for urothelial bladder cancer after failure on PD-(L)1 blockade and chemo, just over a year ago. This was on the basis of the single-cohort EV-201 study, which showed a striking 44% overall remission rate in patients not preselected for nectin-4 expression.

To convert the early green light into full US approval the companies want to use the phase III EV-301 study, which tests a similar second or later-line setting to EV-201, but compares Padcev against chemotherapy. This was stopped early for efficacy last September, but the data are only now being presented at Asco-GU.

Across the 608-strong intent-to-treat population Padcev’s median overall survival benefit is 3.9 months, the 30% reduction in risk of death yielding a p value of 0.001. Risk of progression or death, a secondary endpoint, was reduced by 38% (p<0.001).

So far so good. But subgroup analyses reveal a worrying sign: among EV-301’s 138 female subjects survival favoured chemotherapy, with women given Padcev being at a relative 17% increased risk of death.

Deaths in selected EV-301 subgroups. Adapted from Dr Thomas Powles's presentation at Asco-GU.

Of course, such a post hoc finding has to be treated with caution. It concerns less than a quarter of EV-301’s population, reflecting the demographic profile of advanced urothelial carcinoma, and until it is explored prospectively it remains just a signal in a subgroup.

Still, the analysis will come as a surprise. EV-201 had not suggested a lack of responses in female patients, and Padcev’s label makes no mention of such a possibility. What it does do, however, is warn of embryo-fetal toxicity and say women given the drug should take contraception, as well as citing risk of adverse reactions in the child of a breastfeeding mother on Padcev.

Taken together such risk factors, and suggestion of no benefit versus chemo, might make urologists wary of prescribing Padcev to women. Should EV-301 lead to full US approval these data would be obvious to doctors reading Padcev’s updated label.

On the plus side, overall serious adverse events were balanced across EV-301’s two cohorts, though treatment-related rash, peripheral neuropathy and hyperglycaemia were elevated with Padcev.

From a business perspective, even eliminating female patients as a target population entirely might not cause too big a dent to Padcev’s sales forecasts, since women make up a minority of this cancer type.

And it is still unclear whether such a sex imbalance in benefit might also be seen in the much more important first-line setting. EV-302, the trial supporting this use, is still some way off yielding data, but forecasts no doubt bake in a significant contribution from the front-line setting.

Selected Padcev studies in urothelial bladder cancer
Trial	Setting	Data	Relevance
EV-201	≥2L (post PD-(L)1), single-cohort	ORR 44% (CR 12%)	Ph2 study that secured US accelerated approval
EV-301	≥2L (post PD-(L)1), vs chemo	mOS 12.9mth vs 9.0mth (HR=0.70, p=0.001)	Ph3 study to convert accelerated US approval to full approval
EV-103	1L & 2L, uncontrolled	Keytruda combo: mPFS 12.3mth; ORR 85% in PD-L1-high, 67% in PD-L1-low	Ph1/2 study of various combos
EV-302	1L, Keytruda combo, vs chemo	None (started enrolling Mar 2020)	Ph3 study to support 1L approval
Source: company reports & Asco-GU. https://www.evaluate.com/vantage/articles/events/conferences/asco-gu-confirmatory-padcev-trial-throws-curveball

Roche Eye Med Can Be Injected on Up to 4 Month Interval

 

• Across four studies in diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD), approximately half of people receiving faricimab could be treated every four months in the first year
• Approximately three-quarters of people receiving faricimab could be treated every three months or longer in the first year
• Faricimab showed rapid and consistent improvements in anatomical outcomes including central subfield thickness across all studies
• If approved, faricimab would be the first in a new class of medicine in 15 years for people with nAMD and in close to a decade in DME

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) today announced detailed results from four Phase III studies of its investigational bispecific antibody, faricimab, for the treatment of diabetic macular edema (DME) and neovascular or “wet” age-related macular degeneration (nAMD). The studies consistently showed that faricimab, given at intervals of up to four months, offered non-inferior vision gains compared to aflibercept, given every two months. Approximately half of people eligible for extended dosing with faricimab were able to be treated every four months in the first year in the YOSEMITE and RHINE studies in DME and the TENAYA and LUCERNE studies in nAMD. Faricimab is the first injectable eye medicine to achieve this length of time between treatments in Phase III studies for DME and nAMD. Furthermore, approximately three-quarters of people eligible for extended dosing with faricimab were able to be treated every three months or longer in the first year. Faricimab was generally well-tolerated in all four studies, with no new or unexpected safety signals identified.

Results from the studies will be presented at Angiogenesis, Exudation, and Degeneration 2021, a medical symposium presented by Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine, on Saturday, February 13.

“These faricimab data offer the promise of a new treatment for two common causes of blindness, diabetic macular edema and neovascular age-related macular degeneration," said Jeffrey Heier, M.D., Director of Retinal Research at Ophthalmic Consultants of Boston in Boston, Mass. “Faricimab’s potential to extend time between treatments may benefit those patients who struggle to keep up with the regular physician visits and eye injections needed to preserve their vision.”

https://www.biospace.com/article/releases/new-phase-iii-data-show-genentech-s-faricimab-is-the-first-investigational-injectable-eye-medicine-to-extend-time-between-treatments-up-to-four-months-in-two-leading-causes-of-vision-loss-potentially-reducing-treatment-burden-for-patients/