Controversy Surrounds Biogen and Eisai’s Alzheimer’s Drug Aducanumab

Biogen and Tokyo-based development partner Eisai are embroiled in controversy surrounding their investigational Alzheimer’s drug, aducanumab.

Biogen submitted a Biologics License Application (BLA) to the Food and Drug Administration (FDA) for the approval of aducanumab as a treatment of Alzheimer’s disease (AD) in July and it has been under review ever since. The European Medicines Agency (EMA) also recently began their review. 

Aducanumab (BIIB037) is an investigational human monoclonal antibody being studied for the treatment of AD. If it does indeed prove successful, the drug has the potential to reduce cognitive decline associated with AD and return quality of life and independent living to patients.  If approved, it would be the first drug to make such an impact, raising the stakes all the more.

In March of 2019, Biogen and Eisai pulled the plug on two Phase III trials, ENGAGE and EMERGE, after an independent committee concluded that efficacy in slowing down cognitive decline in AD was unlikely to be found.

Biogen stock was hit hard – the company lost $18 billion in value – and more broadly, the case for the amyloid hypothesis took another critical blow to the bough. 

After further review of follow-up data from the two trials, the partners announced in October 2019 that with exposure to a higher dose, the drug showed “reduced clinical decline in patients with early AD.”

However, David Knopman, a neurologist at Mayo Clinic who was an investigator in the ENGAGE and EMERGE trials, led a paper in the Journal of the Alzheimer’s Association, Alzheimer’s & Dementia disputing the merits of this claim.

Knopman and his colleagues argue that the benefits to the biomarkers amyloid and tau protein may not translate into actual cognitive benefits. The authors are advocating for a new Phase III trial that may lead to more definitive results.

“In contrast, we identified alternative accounts for the apparent drug benefits in post hoc subgroups that are unrelated to dose effects. Biomarker data were consistent with target engagement, but no evidence was presented to correlate biomarker changes to cognitive benefits. Our analysis supports the conduct of a third, phase III trial with high-dose aducanumab,” state the authors.

Knopman, who is conspicuously absent from the advisory committee meeting, told Reuters that he had been recused from the panel due to his involvement in conducting the phase III trials. The FDA has not commented on this situation, but conflict of interest is the usual reason in cases such as this.

Drugs developed on the basis of the amyloid hypothesis attempt to block the formation of amyloid plaques in the brain, which could delay the onset of dementia. This theory has been largely deflated in recent years due to a spate of recent clinical trial failures in drugs.

In February,  Eli Lilly and Roche’s Genentech announced top-line results from a Phase II/III trial testing their respective amyloid-targeting drug candidates, solanezumab and gantenerumab, stating that both failed to meet primary endpoints.

Biogen and Eisai are hopeful of reviving the hypothesis with aducanumab.

https://www.biospace.com/article/controversy-surrounds-biogen-and-eisai-s-alzheimer-s-drug-aducanumab/

Apollo Medical EPS beats by $0.23, beats on revenue; raising FY20 guidance

• Apollo Medical (NASDAQ:AMEH): Q3 GAAP EPS of $0.45 beats by $0.23.
• Revenue of $180.1M (+15.4% Y/Y) beats by $12.83M.
• FY20 guidance: Total revenue of $665.0M-$675.0M vs consensus of $670.8M, raising net income of $110.0M-$120.0M from previously announced $100.0M-$110.0M; raising EBITDA to $182.0M-$194.0M from previously announced $155.0M- $167.0M and adjusted EBITDA to $97.0M-$112.0M from previously announced $75.0M-$90.0M.
• Press Release
• https://seekingalpha.com/news/3631698-apollo-medical-eps-beats-0_23-beats-on-revenue-raising-fy20-guidance
  

Coronavirus spread at workplaces, and what's needed to make them safer

The small town of Watton, Norfolk recently held the unfortunate title of having England's highest rate of infection with COVID-19 relative to population size, following an outbreak at a food factory.

Despite varying degrees of lockdown restrictions due to the pandemic, many people in the UK are still going in to their workplaces. Factories, warehouses, schools, farms and some shops and hotels are all still open, and all have been sites of workplace clusters of transmission of COVID-19.

Indeed, the first case of the virus spreading in a workplace stretches back to the one in a Wuhan market in China in December 2019. The major means to prevent workplace transmission were then identified at a global and national level early in 2020. Yet UK prevention or even control of workplace COVID clusters is failing, sometimes badly.

Week by week, we continue to get new workplace clusters. The latest weekly surveillance report from Public Health England revealed 397 suspected outbreaks in care homes and 334 incidents in workplaces between October 19 and 25. Care homes are, of course, workplaces too.

Attempts to dismiss workplace clusters as simply due to non-work factors such as travel to and from work and crowded housing, which in themselves are occupationally-related, are not supported by available evidence. So what is going wrong and how can it be put right?

The COVID workplace threat to employees, their families and communities can only come primarily from three factors. First, control measures built into government and government agency "COVID-secure" guidance on things like social distancing, masks, ventilation, cleaning, and testing and contact tracing could be inadequate or wrong.

Second, employer working practices could be poor. Thirdly monitoring, inspection and enforcement of guidance by the health and safety regulators who enforce the law—the Health and Safety Executive (HSE) and in some settings local authority health and safety inspectors—could be deficient. Or there could be a combination of all three factors at work. The problem is that there is little investigation into or publicly available data on what is happening.

One high-risk industry that should have been thoroughly checked for months illustrates the problem. In late October, COVID-19 clusters involving hundreds of workers were still being reported in the East of England meat processing industry. This is despite the fact that the specific risks in the sector became clear at the end of 2019 and means to control risks were widely available by May.

The US government has looked at COVID-19 in workers in 115 meat and poultry processing facilities reported by 19 states up to May 2020. From approximately 130,000 workers at these facilities, 4,913 COVID cases and 20 deaths occurred. Factors potentially affecting infection risks included workplace physical distancing, cleaning and hygiene. No similar statistics for the UK are in the public domain.

In Germany, one large meat processing COVID-19 outbreak, also in May 2020, was immediately investigated and a detailed report found spacing, temperature, humidity and ventilation conditions were all factors in how the virus could be spread over long distances. Again, no such reports have apparently been produced in the UK to examine causes and lessons for the future.

Lack of powers

Investigations of COVID-19 workplace clusters in Britain are led by public health staff at a national and local level and not by the HSE, although joint inspections and investigations may occur. This could could mean some investigators lack the powers and possibly the knowledge and skills to enforce measures to stop the spread of the virus.

The HSE has powers to close a workplace hazardous to health. Local authority inspectors have the power to shut workplaces on environmental health grounds. Directors of Public Health do not have such powers.

Nor, for various reasons connected to patient and commercial confidentiality, have details on working conditions in British meat processing plants with COVID-19 clusters been quickly released by either regulators or public health directors. This lack of information and transparency is proving a major handicap to speedy prevention, along with problems on regulatory inspection, industry practice, worker involvement and flawed government policies.

With winter looming, making workplaces COVID-safe rather than simply COVID-secure is therefore proving a challenge for governments, employers, regulators, and workers. It can be done—and has been elsewhere in the world—by applying the science available, adopting best practice in occupational health and safety, and resolving organizational and policy conflicts and confusion.

https://medicalxpress.com/news/2020-11-coronavirus-rapidly-workplaces-safer.html

Regenxbio EPS beats by $1.14, beats on revenue

• Regenxbio (NASDAQ:RGNX): Q3 GAAP EPS of $0.24 beats by $1.14.
• Revenue of $98.9M (+572.8% Y/Y) beats by $74.1M.
• Shares +1.5%.
• Press Release
• https://seekingalpha.com/news/3631476-regenxbio-eps-beats-1_14-beats-on-revenue
  
  

PRA Health Sciences EPS beats by $0.16, beats on revenue; FY20 guidance

• PRA Health Sciences (NASDAQ:PRAH): Q3 Non-GAAP EPS of $1.30 beats by $0.16; GAAP EPS of $1.41 beats by $0.73.
• Revenue of $796.3M (+2.0% Y/Y) beats by $27.16M.
• FY20 guidance: Revenue of $3.120B-$3.150B vs consensus of $3.10B, GAAP net income per diluted share of $3.23-$3.35 and non-GAAP net income per diluted share of $4.61-$4.71 vs consensus of $4.46.
• Press Release
• https://seekingalpha.com/news/3631464-pra-health-sciences-eps-beats-0_16-beats-on-revenue-fy20-guidance
  

McConnell sets sights on stimulus bill by end of the year

• Senate Majority Leader Mitch McConnell said his top priority will be to pass a new economic stimulus bill before the end of the year, he said in a news conference in Kentucky after he won re-election for his seventh term in the Senate.
• Though there are still some Senate races too close to call, it appears that Republicans will keep control of the Senate.
• McConnell said he hopes that "partisan passions that prevented us from doing another rescue package will subside with the election."
• "And I think we need to do it, and I think we need to do it before the end of the year," he said.
• Talks for further fiscal measures to ease the economic burdens of the coronavirus have been stalled for months. The House, controlled by Democrats, passed a $3T stimulus bill in May, then passed a revised $2.2T package in early October, neither of which were taken up by the Senate.
• McConnell had tried twice, unsuccessfully, to pass a half-trillion-dollar program that provided aid for schools and replenished the PPP small loan program. That was blocked by Senate Democrats who said it didn't go far enough and by some Republicans who said it cost too much.
• With the elections over, McConnell seems to be taking a more conciliatory tone. "We have to deal with the Democrats,” he said.
• https://seekingalpha.com/news/3631436-mcconnell-sets-sights-on-stimulus-bill-end-of-year
  

Schools Aren't Driving Covid Infection Rates - Study

The return to schools in the US was memorably fraught with doomsayers like Dr. Fauci who at times allied with unions (particularly in America's biggest districts like in LA, Chicago and New York) to force mayors to agree to lengthy delays of in-person education unless they acquiesced to measures on staffing and resources intended to ensure "teacher safety".

Months later, the controversy that surrounded President Trump's attempt to force schools around the country to reopen, something that the media raised a major stink about (accusing the president of endangering the nation's children for the sake of something as trivial as "the economy") has all but faded.

A surfeit of testing in the US and across Europe that was carefully monitored and studied by researchers has been carried out. And as Bloomberg reports, positivity rates in places like NYC were "extremely low" - less than 0.2%.

Though we never saw the surge in cases that some feared reopening schools might trigger, infection rates in schools have more or less tracked the rates from their surrounding community.

“You can’t really pull the school out from the community,” said Walter Gilliam, an education policy researcher at the Yale School of Medicine. “The biggest part of this, really, is how do you keep transmission rates in a county to a level that the schools even have a chance? If the transmission rates are too high, there's just almost nothing they could do to keep it from getting into schools."

So far, the data show that children are not major spreaders of the virus a) among themselves b) among each other and c) among their parents.

If rates of spread in the community are high, then rates in the schools will be high. This is the reasoning that undergirds decisions in France, Germany etc. that revived most of the restrictions from the springtime lockdowns, with the exception of the schools.

These trends hold true around the world, not just in the US. Research by a third-party nonprofit called Insights for Education examined data from 191 countries and found that the trend was virtually the same everywhere, with rates of infection in K-12 school systems mirroring rates in the surrounding community.

Other early evidence similarly suggested that schools don’t inherently become virus hot spots. Insights for Education, an independent foundation that advises education departments and ministries, examined data from 191 countries between Feb. 10 and Sept. 29 and found "no consistent pattern between school status and infection levels."

In Spain, a second wave of the virus began before schools reopened. One analysis there found that in one region cases dropped three weeks after schools reopened, in one region cases stayed flat and in others case numbers continued rising at the same rate. A new project that is collecting data on reopenings in the U.S., the COVID-19 School Response Dashboard, examined data from more than 5,000 schools across all 50 U.S. states and found that at a late-September peak, about 3% of schools reported outbreaks of five or more infections.

But, seeing as this is a Bloomberg report, the reporters note that just because 'the experts' were wrong about COVID-19 and its risk to the public education system doesn't mean they were wrong about...well...everything else, too.

In the US, school openings have been complicated and confused by a White House that has downplayed the risks of in-person instruction and federal agencies that have never issued clear guidelines for safe practices. That’s left policy-making to state and local governments that are rushing to respond to the changing virus and what’s learned about it.

Whether it’s safe to open schools, said Rainu Kaushal, a clinical researcher at Cornell University’s medical school, Weill Cornell Medicine, in New York City, depends largely on two factors: How serious the spread of the virus is in the community and how seriously the community is taking precautions against the virus.

She said schools also need to be nimble.

"This virus situation evolves so rapidly that one can only make the best decision for the next few weeks," she said. "And then you really have to take stock again."

To be sure, while K-12 schools haven't proved nearly as dangerous as advertised, college students remain a risk, with reports on college campuses showing large universities around the country becoming veritable petri dishes of disease. Epidemiologists will be watching the numbers as the winter progresses to see whether the virus continues to intensify heading into the new year, or whether rates finally begin to subside.

https://www.zerohedge.com/geopolitical/another-covid-19-myth-busted-schools-arent-driving-infection-rates-study-finds