FDA OKs Boston Scientific next-gen heart device

The FDA approves Boston Scientific’s (NYSE:BSX) next-generation Watchman FLX Left Atrial Appendage Closure (LAAC) device to reduce the risk of stroke in patients with non-valvular atrial fibrillation who need an alternative to oral blood thinners.

The left atrial appendage is where blood clots typically form in these patients.

Commercial launch will begin immediately.

The device was CE Mark’d in March 2019.

https://seekingalpha.com/news/3593361-fda-oks-boston-scientific-next-gen-heart-device

Intuitive Surgical EPS beats by $0.62, beats on revenue

Intuitive Surgical (NASDAQ:ISRG): Q2 Non-GAAP EPS of $1.11 beats by $0.62; GAAP EPS of $0.57 misses by $0.14.

Revenue of $852.1M (-21.8% Y/Y) beats by $215.26M.

178 (-3.5% Y/Y) daVinci systems shipped vs. consensus of 141.

Shares +1.9%.

Press Release

https://seekingalpha.com/news/3593319-intuitive-surgical-eps-beats-0_62-beats-on-revenue

Acadia fails to expand use of antipsychotic to treat depression

Acadia Pharmaceuticals reported negative results Monday from a pair of late-stage clinical trials seeking to expand the use of its antipsychotic medicine Nuplazid to patients with major depressive disorder.

The two identically designed Phase 3 clinical trials involved 300 patients who hadn’t responded well to currently approved depression treatments. In both studies, Nuplazid failed to demonstrate an anti-depressive benefit compared to a placebo when given to patients alongside their current medicines.

Patients given Nuplazid saw their scores on a measure known as the Hamilton Depression Rating Scale drop 9 points over 15 days, compared to a decrease of 8.1 points for those in the placebo group.

Depression studies are notoriously difficult to pull off successfully, and often require multiple attempts to achieve positive results. However, Acadia said it has no immediate plans to conduct another depression study at this time.

The FDA is currently reviewing Nuplazid as a treatment for hallucinations and delusions associated with dementia-related psychosis, with an approval decision date set for April 3, 2021.

Nuplazid is currently approved to treat reduce hallucinations and psychotic symptoms in people with Parkinson’s disease. Sales in 2019 totaled $339 million and are expected to reach $437 million this year.

Acadia fails in attempt to expand use of antipsychotic to treat patients with depression

Actual Covid-19 case count may be 6-24 X higher than official estimates – CDC study

The true number of coronavirus cases in the U.S. could be anywhere from six to 24 times higher than the confirmed number of cases, depending on location, according to a large federal study that relied on data from 10 U.S. cities and states.

The vast majority of Americans, however, are still vulnerable to Covid-19.

The study, published Tuesday in JAMA Internal Medicine, relied on serological tests — blood screens that search for antibodies to the virus and that determine whether someone was previously infected. They are different from diagnostic tests, which only detect people who currently have the virus, called SARS-CoV-2.

Overall, an estimated 1% of people in the San Francisco Bay Area have had Covid-19, while 6.9% of people in New York City have, according to the paper’s authors, who included researchers at the Centers for Disease Control and Prevention and state health departments. In seven of the 10 sites, the estimated number of cases was 10 times the number of reported cases.

The study was based on tests from more than 16,000 people across the 10 sites, but one limitation is that it relies on old data. The San Francisco samples were collected from April 23 to 27, while the New York tests were on blood from March 23 to April 1. The latest tests were conducted in May, and a lot can change during two months in the course of an outbreak. In South Florida, for example, researchers estimated that 1.9% of the population had antibodies to the virus. But that figure is based on samples collected from April 6 to 10, and given the spread of the virus since then in the state, the number now would certainly be some amount higher.

Still, the data reflect what CDC Director Robert Redfield recently said — that true case numbers are 10 times higher than confirmed diagnoses. Confirmed cases in the U.S. stand at more than 3.8 million.

The data underscore two other points: that testing in the U.S. is not capturing the full scope of the outbreak, and that even hard-hit communities are not close to reaching a herd immunity threshold — where enough people are immune from the virus (which scientists expect will happen for some amount of time after an initial infection) to slow down its spread to the point that unprotected people have a natural buffer.

“The study rebukes the idea that current population-wide levels of acquired immunity (so-called herd immunity) will pose any substantial impediment to the propagation of SARS-CoV-2 in the U.S., at least for now,” infectious disease experts Tyler Brown and Rochelle Walensky of Massachusetts General Hospital wrote in an editorial accompanying the study. Experts estimate that 60% to 70% of people in a given area would need to be protected from the virus — either through recovering from an infection or vaccination — to reach herd immunity.

Other locations included in the study and the estimated levels of antibodies in their residents:

• Western Washington: 1.1%
• Louisiana: 5.8%
• The Philadelphia area: 3.2%
• Missouri: 2.7%
• Utah: 2.2%
• Connecticut: 4.9%
• The Minneapolis-St. Paul area: 2.4%

Overall, the researchers found that there was no association between infection rates and age or sex.

The results fit with other serosurveys that have found just a few percent of people in a given place have been infected with the SARS-CoV-2 virus, which causes the disease Covid-19. There have been a few outliers: One study in the hard-hit Boston suburb of Chelsea estimated that 30% of people had been exposed to the virus, while another survey in a German town where a carnival drove an outbreak found 14% of residents had antibodies.

Still, the new study landed on different estimates for New York City than a state-run survey released in April, which found that 1 in 5 people in the city had antibodies. The disparate results highlight how study design — such as how participants are recruited or what blood samples are included — can influence findings.

The new study relied on leftover blood samples collected from patients who sought medical care for any reason from March through May. Because so many appointments and procedures were canceled then, and because so many people were avoiding medical care during stay-at-home periods, the samples “are likely not representative of a typical prepandemic cohort,” Brown and Walensky wrote.

Experts note that the inability of diagnostic testing to keep up with cases is not just limited to problems with the tests, which have included a botched rollout, overwhelmed labs, and supply shortages. It’s also that some 20% to 40% of Covid-19 infections are asymptomatic. Those people can still spread the virus, as can people who eventually develop symptoms but don’t feel sick yet — which has complicated efforts to rein in the spread.

Researchers also stress that it’s still not confirmed if people who recover from Covid-19 are protected or for how long, or what levels (or titer) of antibody would be required to confer immunity. Some people with Covid-19 may not generate a robust antibody response, perhaps depending on how sick they get, though that remains an open question as well.

“At present, the relationship between detectable antibodies to SARS-CoV-2 and protective immunity against future infection is not known,” the study’s authors wrote. “Extrapolating these estimates to make assumptions about population immunity should not be done until more is known about the correlations between the presence, titer, and duration of antibodies and protection against this novel, emerging disease.”

Actual Covid-19 case count could be 6 to 24 times higher than official estimates, CDC study shows

Over 100,000 sign up for coronavirus vaccine testing

More than 107,000 Americans have volunteered to participate in clinical trials for potential coronavirus vaccines as of last week, according to a USA Today report.

While the number is still shy of the needed 120,000, or 30,000 for each of the four drugmakers launching phase three trials, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the quick sign-ups are a positive sign, according to the newspaper.

“That’s why we’re optimistic that we’re going to be able to get the trials enrolled in an expeditious way. I think we can do what we need to do,” Fauci said.

“I would say it’s very encouraging at this stage to have 107,000 volunteers,” Barry Bloom, a professor of public health at Harvard’s Chan School of Public Health, told the newspaper.

To accelerate the trial process, the National Institutes of Health earlier this month launched the COVID-19 Prevention Trials Network, combining four pre-existing trial networks that have been used as far back as the AIDS crisis.

“It would take literally years to build up a network that I’ve build up over the last 30 years. So why do it? We’re going to use what we have,” Fauci said.

“Each vaccine needs to be tested on about 30,000 volunteers,” NIH Director Francis Collins said in June. “We don’t believe that we have enough power in the analysis to be able to document the vaccine works unless you get to roughly that number.”

The Food and Drug Administration is prioritizing the demographics that have been particularly hard-hit by the pandemic for testing, including minorities, the elderly and people with pre-existing medical conditions, but the trials will adhere to the same strict safety standards as other vaccines.

“The guidelines for these trials are really clear. They will be scientifically rigorous and there are no shortcuts,” Bloom told USA Today.

https://thehill.com/policy/healthcare/508073-more-than-100000-have-signed-up-for-coronavirus-vaccine-testing

Moderna’s $37B market cap ‘too high, despite COVID-19 vaccine’ – JPMorgan

JP Morgan has downgraded its valuation of Moderna, saying its $37 billion market cap is way too high even if its COVID-19 vaccine mRNA-1273 succeeds in clinical trials.

Moderna’s share price has rocketed 385% this year, driven by the development of mRNA-1273, but the analysts think there are too many unknowns surrounding the coronavirus pandemic and the prospects for a vaccine to justify its valuation.

They have downgraded the stock from overweight to neutral, stressing however that the move “is not a call on any sort of diminished expectations around the company or mRNA-1273.”

More important are questions such as how long the pandemic will last, what price vaccine makers will be able to charge, and how many effective vaccines will become available, says JP Morgan.

Just yesterday, there were positive preliminary trial results with two other coronavirus vaccines – from Oxford University/AstraZeneca and CanSino Biologics – and at last count there were 24 candidates in clinical development.

mRNA-1273 – one of five vaccines in the clinical pipeline based on RNA – is also one of the furthest ahead in development, having already started phase 3 testing.

Earlier this month, Moderna reported initial clinical results from a US National Institutes of Health (NIH) study showing that two doses of the shot was able to stimulate neutralising antibodies against SARS-CoV-2, the virus that causes COVID-19.

“We remain bullish on Moderna’s long-term outlook, disruptive platform (in the vaccine space and otherwise), and chances of being one of the first companies to bring a COVID-19 vaccine to market,” write the JP Morgan analysts in a research note.

More positive data readouts could drive the company’s share price and market cap still higher, but “we’re simply unable to continue to fundamentally justify it,” they add.

They also think success with the COVID-19 candidate will read through to the rest of Moderna’s pipeline, which includes other vaccine candidates as well as RNA-based drugs for cancer immunotherapy and other diseases.

At the moment JP Morgan ascribes a value of $25 billion for Moderna’s mRNA platform, which is substantially above any other companies it covers.

They place a value for mRNA-1273 of $16 per Moderna share – trading at more than $82 today – with a 60% chance of success for the programme and peak sales estimates of $4.2 billion to 6.4 billion, depending on the duration of the pandemic.

The top end of those estimates apply if SARS-CoV-2 becomes endemic or the pandemic lasts through 2025 with people requiring annual shots for protection.

The lower end of the model – which JP Morgan give a 10% probability to – is that the pandemic lasts through 2022.

Moderna’s $37B market cap is too high, despite COVID-19 vaccine; analyst

Synairgen joins the 2020 coronavirus winners club

A small trial of inhaled interferon marks a 30-fold increase in Synairgen stock since January, but the endpoints warrant scrutiny.

With investors and governments itching to analyse the first clinical data from Astrazeneca/Oxford University’s Covid-19 vaccine today, it was in fact a different UK company – the tiny biotech Synairgen – that seized most of the morning’s attention.

Synairgen is a group focused on respiratory disease, whose key technological advance has been an inhaled form of interferon beta-1a. But its masterstroke was to begin a study of this in Covid-19, and the results of this small trial, toplined today, have sent its stock up 400%, notwithstanding questions over what the company has actually demonstrated.

Even more remarkably, Synairgen now stands over 30 times higher than it did at the start of 2020, putting it in line to be one of this year’s best-performing biotechs. But even after the share price surge its market cap is still just £250m ($315m).

The study of Synairgen’s inhaled interferon beta-1a, a project coded SNG001, has two parts, made up of 101 hospitalised patients and 120 in the home setting. It was the former that generated what the markets today deemed a clinical win.

Endpoints?

Still, Synairgen has disclosed very little about its study’s primary endpoint of absolute 28-day improvement versus placebo on an eight-point ordinal scale on which 0 represents “well” and 8 is “death”.

Instead, it press-released three apparently secondary efficacy measures: developing severe disease, recovery as defined by no limitation of activities or no evidence of infection, and improvement in breathlessness, all by day 16. All were backed by p values that were below 0.05, but at no point did Synairgen’s press release claim that any was statistically significant.

On a media call the group accepted that the p values had not been adjusted for multiplicity – 10 or 15 analyses had been done, it revealed – leaving open the possibility that they lacked statistical significance. Moreover, it cited an extremely wide confidence interval range, suggesting a high likelihood of chance.

The group was also evasive as regards the primary endpoint of absolute improvement at 28 days, its chief executive, Richard Marsden, saying he did not have these results at hand.

Professor Tom Wilkinson, the study’s lead investigator, argued that this involved a complicated statistical analysis. “We have performed that analysis [and it] demonstrates that there was a clear treatment effect. It was statistically significant,” he stated.

Management argued that the primary outcome was captured in the measures of improvement it cited for day 16, but the absence of a primary efficacy analysis – a study’s most important metric – is puzzling.

UK biotech win

All that said, perhaps given Synairgen’s market cap a borderline numerical benefit in what is ultimately a small trial can be called a win. After all, every other company working on Covid-19 that has revealed clinical data – most with multi billion-dollar valuations – has raised some red flags.

It is also clear that Synairgen needs more trials of SNG001 and more money to run these, but today’s announcement certainly raises the group’s profile. Interestingly, its study’s at-home part has proved difficult to enrol, and “completion will depend on there being a second wave [of Covid-19 in the UK], which we believe will happen”, said Mr Marsden.

Synairgen, a University of Southampton spin-out, had earlier focused SNG001 at asthma and COPD, and its greatest success until now was a $7m tie-up with Astrazeneca. Perhaps the Covid-19 data will attract further funding, though this will likely come from investors; the UK government has so far focused its spending efforts largely on securing vaccine supply.

Today, the UK government announced that it had secured 30 million doses of Biontech/Pfizer’s BNT162, for delivery in 2020/21, and 60-100 million doses of Valneva’s VLA2001. An agreement to supply the UK with 100 million doses of the Astrazeneca/Oxford University vaccine AZD1222 was also reportedly struck in May.

Whatever doubts might remain about Synairgen’s statistical rigor, the company’s co-founder Stephen Holgate insisted: “We do feel confident that there’s a real biological and clinical signal here within the data.”

https://www.evaluate.com/vantage/articles/news/trial-results/synairgen-joins-2020-coronavirus-winners-club