Empty middle airplane seat could cut coronavirus exposure by up to 57% - CDC

 A vacant middle airplane seat could cut the risk of exposure to coronavirus by 23% to 57% compared with a full flight, according to a study on physical distancing onboard released on Wednesday.

Researchers from the U.S. Centers for Disease Control and Prevention and Kansas State University based their findings on laboratory modeling of exposure to SARS-CoV-2, the virus which causes COVID-19, on single-aisle and twin-aisle aircraft in November 2020.

The research is backed by results of a separate investigation of coronavirus transmission on a 10-hour international flight in March 2020, in which 16 people were infected, they said. That study found 75% of infected passengers were seated within two rows of a symptomatic passenger.

U.S. airlines blocked middle seats early in the pandemic but have gradually opened them up, citing studies showing low transmission risk if everyone onboard wears a mask. Delta Air Lines is lifting its seating block beginning May 1.

https://www.marketscreener.com/news/latest/Empty-middle-airplane-seat-could-cut-coronavirus-exposure-by-up-to-57-CDC--32968771/

Bluebird, PsiOxus show oncolytic virus boosts CAR-T in solid tumors

 Bluebird bio has shown cancer gene therapy vectors boost the efficacy of its CAR-T therapy in mice. The study assessed the effect of giving bluebird’s anti-EGFR CAR-T cells in combination with vectors in development at PsiOxus Therapeutics. 

PsiOxus and bluebird began exploring the combination in light of the limitations of monotherapies in solid tumors. CAR-T cells have underwhelmed so far in solid tumors, potentially because the tumor microenvironment stops them from infiltrating the cancer and killing its cells. It may be necessary to tackle the immunosuppressive environment to make CAR-T cells effective in solid tumors.

The bluebird-PsiOxus work assessed the ability of cancer gene therapy vectors based on the oncolytic adenovirus enadenotucirev to make the microenvironment more hospitable to T cells. The vectors encoded for immunomodulatory molecules to encourage T-cell recruitment and activation.

In mice implanted with human lung cancer A549 xenografts, neither the anti-EGFR CAR-T cells nor the cancer gene therapy vectors showed efficacy or delayed disease progression when administered as a single agent. However, in combination, the drug candidates cleared the xenograft and pulmonary metastases. Expression of the virus-encoded transgenes was evident.

“These data validate the potential of our T-SIGn platform to reprogram the tumor microenvironment such that CAR-T cells are recruited, activated and sustained within solid tumors to yield efficacy,” John Beadle, CEO of PsiOxus, said in a statement. Buoyed by the findings, PsiOxus plans to continue evaluating its T-SIGn vectors in combination with T-cell therapeutics in solid tumors. 

PsiOxus is already testing one of its vector programs, NG-641, in humans. A first-in-human study in patients with metastatic or advanced epithelial tumors began last year, and a checkpoint inhibitor combination trial is in the works. Another vector program, NG-347, is at the IND-enabling stage.

https://www.fiercebiotech.com/biotech/bluebird-psioxus-show-oncolytic-virus-boosts-car-t-solid-tumors

Europe won't renew AstraZeneca, J&J COVID-19 vaccine contracts next year: report

 Amid delivery delays and concerns over rare but serious blood clots for the AstraZeneca and Johnson & Johnson COVID-19 shots, European officials are looking elsewhere for next year's supply. 

The European Commission has opted against renewing its vaccine contracts with AstraZeneca and J&J once they expire at the end of the year, Italian newspaper La Stampa reported Wednesday, citing an unnamed source from the Italian health ministry. Reuters also picked up the story.

Both shots have come under scrutiny over rare but serious cases of blood clots in people who had received the vaccines, prompting several countries to halt use of the AZ shot while the European Medicines Agency completed a follow-up safety review. Meanwhile, AstraZeneca has struggled to meet the delivery targets it originally laid out, while J&J just this week said it would delay its vaccine rollout in the bloc over safety concerns.

“The European Commission, in agreement with the leaders of many (EU) countries, has decided that the contracts with the companies that produce (viral vector) vaccines that are valid for the current year will not be renewed at their expiry,” La Stampa reported.

At the same time, the Commission is demanding answers from J&J over its “completely unexpected” delay, an EU official told Reuters Tuesday.

J&J and AstraZeneca did not immediately reply to Fierce Pharma’s request for comment.

AstraZeneca had originally committed to delivering 90 million doses to the EU in the first quarter of 2021, according to reports, but cut that target to 31 million in January, sparking a heated back-and-forth between the company and Brussels officials. It eventually said it would push to deliver 40 million doses, but in mid-March, dialed its estimate back to 30 million doses.

In last month’s supply update, AZ said it would aim to deliver 100 million doses to Europe in the first half of the year, a reduction of two-thirds from the company's prior target of 300 million doses.

Johnson & Johnson, for its part, let European officials know it was “under stress” to meet its second-quarter delivery target back in early March. J&J stood firm on its “commitment to deliver 200 million doses of its single-dose COVID-19 vaccine candidate to the EU in 2021 starting in the second quarter.” A Reuters source noted J&J might still be able to hit that target.

Now, however, J&J is delaying its rollout for another reason. On Tuesday, the drugmaker said the U.S. Centers for Disease Control and Prevention and the Food and Drug Administration had recommended a pause on the vaccine’s use out of an “an abundance of caution” amid investigations into an extremely rare potential side effect involving blood clots with low platelets.

The company says it has been reviewing the cases with Europe, too, and has made the call to delay its rollout there and pause vaccinations in all Janssen COVID-19 trials as it updates its guidance for investigators and participants.

Of the nearly 7 million people who’ve received J&J’s shot in the U.S., six recipients—all women between the ages of 18 and 48—were diagnosed with rare clots afterward, according to the FDA. One of those people died and another is in critical condition.

"We have been working closely with medical experts and health authorities, and we strongly support the open communication of this information to healthcare professionals and the public," J&J said in its statement Tuesday.

For Europe, the bloc will now likely lean on the mRNA vaccines from Pfizer and BioNTech and Moderna in a big way, La Stampa reported. The European Union is keeping all options on the table as it tunes its pandemic response for 2022 and beyond, a European Commission spokesperson told the Italian daily.

Officials are seeking member-state approval to secure up to 1.8 billion Pfizer-BioNTech doses for 2022 and 2023, Reuters reported last week, citing an unnamed EU official. About half of those doses will be optional. Meanwhile, Comirnaty's price tag is ticking up. 

The EU is reportedly negotiating the new Pfizer contract at a price of €19.50 ($23.22) per dose, Bulgarian Prime Minister Boyko Borissov said Sunday, as quoted by Business Today. The price was originally €12 per dose, and has since increased to €15.5, he said. 

https://www.fiercepharma.com/pharma/astrazeneca-j-j-covid-19-vaccine-contracts-won-t-be-renewed-europe-next-year-report

Gilead snags 2nd Trodelvy nod—in bladder cancer—but Seagen, Astellas set high bar

 On the heels of turning a conditional FDA nod for Trodelvy in triple-negative breast cancer into a full one, Gilead Sciences has snatched a second green light for the antibody-drug conjugate, this time in bladder cancer. But thanks to competitive data from a rival, pharma watchers have low sales expectations for the new indication.

The FDA has granted accelerated approval of Trodelvy to treat patients with locally advanced or metastatic urothelial cancer who have tried two prior therapies, including a platinum-based chemo and a PD-1/L1 checkpoint inhibitor, Gilead said Tuesday.

Bladder cancer wasn’t a major driver in Gilead’s decision to spend $21 billion on Trodelvy’s developer, Immunomedics. But the drug could have had more opportunity if it weren’t for the even better clinical data that Seagen and partner Astellas recently posted for their own antibody-drug conjugate, Padcev.

Trodelvy earned its bladder cancer go-ahead with early results from the phase 2 Trophy-U-01 study. Of the 112 patients evaluable for efficacy, 27.7% responded to Trodelvy with significant tumor shrinkage, with responses lasting a median 7.2 months. Gilead’s now running a phase 3 confirmatory trial dubbed Tropics-04, hoping to show the drug can extend patients’ lives and convert the accelerated green light into a full one.

But Padcev already has all those data, and it appears to be more powerful than the Gilead med. In third-line bladder cancer, Padcev cut the risk of death by 30% over chemotherapy in the phase 3 EV-301 trial. As for tumor shrinkage, Padcev’s overall response rate stood at 40.6%, which appeared to be better than Trodelvy’s showing in its own trial, according to results updated at this year’s ASCO GU event.

While cross-trial comparisons have their intrinsic problems, analysts use them for competition analysis anyway. Based on those data, they had already declared Padcev the winner between the two in bladder cancer.

Two oncology experts labeled Padcev’s data as “practice changing” in third-line treatment and “were excited for the drug to move into earlier lines of therapy and to use the drug in combination with [Merck’s] Keytruda,” SVB Leerink analyst Andrew Berens wrote in an investor note right after the ASCO GU event in February.

As for Trodelvy, one expert “felt the enthusiasm was much more modest” in late-line bladder cancer, and both industry leaders expressed concern about the drug’s toxicity profile. Trodelvy bears a boxed warning for potentially life-threatening neutropenia and severe diarrhea.

Gilead’s commercial focus for Trodelvy is expanding its use from academic medical centers—which generally have more experience managing serious side effects—into the community setting, Porges summarized in a separate February note after hosting Gilead Chief Commercial Officer Johanna Mercier and Chief Financial Officer Andrew Dickinson at an investor event. The company believes targeted education and emphasizing the survival benefit seen in the drug’s TNBC indication could help it increase share in the community setting, Porges said.

Investors’ focus is on Trodelvy’s upcoming phase 3 data in the much larger HR-positive, HER2-negative breast cancer indication, which are expected later this year. Another potential major upside for the drug lies in non-small cell lung cancer, with a phase 2 readout possible in 2022.

Analysts have previously questioned whether Gilead paid too much for Immunomedics. But the company believes it can justify that heavy investment if it achieves success in just one more disease between either HR-positive breast cancer or NSCLC, Porges noted.

https://www.fiercepharma.com/marketing/a-roll-gilead-snags-2nd-trodelvy-nod-bladder-cancer-but-efficacy-bar-has-gone-up

Apple, Google block NHS contact tracing app update on privacy grounds

 A scheduled update to the NHS COVID-19 app has been blocked because it allows location tracking – something prohibited by Apple and Google, which developed some of the code it uses. 

The new version of the app used in England and Wales was due to become available today to coincide with the relaxation of lockdown rules, with the public now able to attend venues such as non-essential shops, pub beer garden, gyms and hairdressers.

The new version of the app would ask users to upload the log of venues they had checked into using QR codes if they subsequently tested positive for COVID-19.

This type of location tracking is however explicitly banned by Apple and Google on privacy grounds, and the two tech giants have now refused to allow the new version to be downloaded from their app stores. The older version of the app is however still available.

Apple and Google collaborated on the development of the contact tracing system that allows people who have been exposed to SARS-CoV-2 to provide a notification of their status, and warn other users of the app who have been in close contact with them to self-isolate.

It’s the latest embarrassing setback for the NHS app after the initial model was canned last year after field trials on the Isle of Wight found it was all-but ineffective, despite millions of pounds of development.

That home-grown version was unable to operate effectively because of a feature of Apple’s iPhone operating system, specifically that apps go to sleep when not in use and cannot be activated by Bluetooth – the technology used to determine close contacts.

It also relied on a centralised database off registered participants, a move which sparked concerns about infringement of civil liberties before it was abandoned.

The Department of Health and Social Care (DHSC), which is responsible for the app, subsequently swapped to the exposure notification platform developed by Apple/Google, but in so doing signed up to agreement terms that prohibit location tracing.

The app used in Scotland isn’t affected because it has developed a separate app for venue check-ins, rather than building that functionality into the Protect Scotland contact-tracing app, according to the BBC.

Commenting on the delay, Jim Killock, executive director of the UK Open Rights Group (ORG) which campaigns to protect privacy and free speech online, said the proposed changes “would have a significant impact on user privacy”.

He went on: “Unfortunately, the government have not put in place any legal safeguards, and the ICO [Information Commissioner’s Office] continues to be reluctant to challenge them.”

The ORG has previously taken the government to task – and specifically Health Secretary Matt Hancock – for dismissing calls for a data protection impact assessment (DPIA) for the tracing system as “bureaucracy”, even though legal advisors indicated one was required.

A spokesperson for the DHSC told Sky news that the new feature had simply been “delayed”, adding that “we remain in discussions with our partners to provide beneficial updates to the app which protect the public”.

https://pharmaphorum.com/news/apple-google-block-nhs-contact-tracing-app-update-on-privacy-grounds/

Bausch boosted ahead of eye spin-off

 Despite various products being marketed for dry eye disease, there is still an unmet need in the disorder. This explains why the late-stage pipeline is relatively crowded, with many different mechanisms being tested.

One of these projects, Bausch Health Companies' NOV03, yesterday succeeded in its first phase 3 trial, Gobi. The project will have to repeat the trick in its second pivotal study, Mojave, but if it does NOV03 could become a key product for the new-look Bausch & Lomb, which is set to spin off from its parent company.

Still, getting products approved for dry eye disease has not always been easy – just ask Kala, which finally got the go-ahead for Eysuvis last year after having to carry out three pivotal trials. One of Eysuvis’s initial studies had shown a benefit on signs but not symptoms of dry eye disease, which spurred the FDA to ask for data from a third trial (Persistence pays off for Kala, March 10, 2020).

Signs and symptoms

In a positive sign for NOV03, Gobi hit on both signs and symptoms. On signs, there was a statistically significant reduction in total corneal fluorescein staining, a measure of eye damage, with NOV03 versus saline at 57 days. On symptoms, there was a statistically significant decrease in the dryness score with NOV03 versus saline at 57 days. Bausch said the p values for both co-primary endpoints were less than 0.001, but did not disclose the numerical reductions.

On the face of it the win looks impressive. But Evercore ISI’s Umer Raffat noted that an oil-based eye drop would have been a more stringent comparator, though he added that Bausch had presumably been guided by the FDA on the comparator to use.

He also questioned whether the project could ultimately compete with approved dry eye drugs like Abbvie’s Restasis and Novartis’s Xiidra – unlike studies of these products, the Gobi trial did not allow the use of artificial tears, a mainstay of dry eye therapy.

Finally, NOV03 is given four times per day, which could cause problems with compliance.

Stifel analysts were more optimistic about NOV03’s chances, saying the data, along with the project's novel mechanism, “position it perfectly” in the dry eye disease landscape. The semiflourinated alkane is designed to improve the function of the meibomian glands in the eye; these are responsible for secreting an oil that helps keep the eyes moist, and Bausch says their dysfunction is the cause of most cases of dry eye disease.

NOV03 is already marketed in Europe as Evotears by its originator, Novaliq. Bausch licensed the asset in the US and Canada in 2019.

Room for improvement

There is room for improvement in the treatment of dry eye disease. Stifel noted that the likes of Restasis and Xiidra do not provide patients with full relief and that, “due to the inadequacies of current therapies”, only two million of the 16 million US dry eye disease patients are receiving treatment.

Despite its shortcomings Xiidra is still forecast to make $688m in 2026, according to Evaluate Pharma, and tempted Novartis to shell out $3.4bn, so perhaps it is no wonder that many groups are still trying to crack dry eye disease.

One of the more interesting is Oyster Point, which has reformulated smoking-cessation drug Chantix as a nasal spray known as OC-01. The company is expecting an approval decision in October after posting positive pivotal data last year; only one of the doses tested improved symptoms of dry eye (Remember Chantix? It’s back – for dry eye disease, May 11, 2020).

Only one pipeline project, Aldeyra’s reproxalap, currently has sellside forecasts attached – Evaluate Pharma consensus puts 2026 dry eye sales at $391m. The Tranquility and Tranquility-2 phase 3 trials, evaluating signs of dry eye disease, are due to read out in the second half.

Ultimately, several different mechanisms might be needed to address this underserved market, Stifel reckons. To get a piece of it, all Bausch now needs to do is replicate the Gobi results in Mojave.

Selected novel agents in late-stage development for dry eye disease
Project	Company	Description	Note
Filed
OC-01	Oyster Point Pharma	Nicotinic acetylcholine receptor agonist, nasal spray	Reformulation of Chantix; Pdufa date on October 17, 2021
Phase 3
SkQ1	Essex Bio-Technology/Mitotech	Mitochondria-targeted antioxidant	Ph3 Vista-2 study hit in Feb 2021, Vista-3 study planned
Nov-03	Bausch Health Companies/Novaliq	Lipid regulator	Ph3 Gobi study hit Apr 2021, Mojave study completes Sep 2021
Reproxalap ophthalmic solution	Aldeyra Therapeutics	Aldehyde inhibitor	Ph3 Tranquility & Tranquility-2 planned to start H1, both studies to read out H2 2021
Tivanisiran	Pharmamar	RNAi eye drop inhibiting TRPV-1	Ph3 SYL1001 _V study in dry eye with Sjögren 's Syndrome began Mar 2021
Tavilermide	Mimetogen Pharmaceuticals	Nerve growth factor mimetic	Ph3 MIM-728 study completed enrolment in Mar 2020, results had been due in Q4 2020
RGN-259	Regenerx Biopharmaceuticals/GtreeBNT	Thymosin β-4 receptor agonist	Ph3 Arise-3 study failed in Mar 2021 but companies plan to meet FDA
HL036	Daewoong Pharmaceutical/Hanall Biopharma	TNFa inhibitor	Ph3 Velos-2 study failed in Jan 2020 but showed some benefits; second ph3 completes Feb 2022
Source: Evaluate Pharma, clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/trial-results/bausch-boosted-ahead-eye-spin

Brazil's P1 coronavirus variant mutating, may become more dangerous: study

 Brazil’s P1 coronavirus variant, behind a deadly COVID-19 surge in the Latin American country that has raised international alarm, is mutating in ways that could make it better able to evade antibodies, according to scientists studying the virus.

Research conducted by the public health institute Fiocruz into the variants circulating in Brazil found mutations in the spike region of the virus that is used to enter and infect cells.

Those changes, the scientists said, could make the virus more resistant to vaccines - which target the spike protein - with potentially grave implications for the severity of the outbreak in Latin America’s most populous nation.

“We believe it’s another escape mechanism the virus is creating to evade the response of antibodies,” said Felipe Naveca, one of the authors of the study and part of Fiocruz in the Amazon city of Manaus, where the P1 variant is believed to have originated.

Naveca said the changes appeared to be similar to the mutations seen in the even more aggressive South African variant, against which studies have shown some vaccines have substantially reduced efficacy.

“This is particularly worrying because the virus is continuing to accelerate in its evolution,” he added.

Studies have shown the P1 variant to be as much as 2.5 times more contagious than the original coronavirus and more resistant to antibodies.

On Tuesday, France suspended all flights to and from Brazil in a bid to prevent the variant’s spread as Latin America’s largest economy becomes increasingly isolated.

The variant, which has quickly become dominant in Brazil, is thought to be a large factor behind a massive second wave that has brought the country’s death toll to over 350,000 - the second highest in the world behind the United States.

Brazil’s outbreak is also increasingly affecting younger people, with hospital data showing that in March more than half of all patients in intensive care were aged 40 or younger.

For Ester Sabino, a scientist at the faculty of medicine of the University of Sao Paulo who led the first genome sequencing of the coronavirus in Brazil, the mutations of the P1 variant are not surprising given the fast pace of transmission.

“If you have a high level of transmission, like you have in Brazil at the moment, your risk of new mutations and variants increases,” she said.

So far vaccines, such as those developed by AstraZeneca and China’s Sinovac, have proven effective against the Brazilian variant but Sabino said further mutations could put that at risk.

“It’s a real possibility,” she said.

https://www.reuters.com/article/us-health-coronavirus-brazil-variant/brazils-p1-coronavirus-variant-mutating-may-become-more-dangerous-study-idUSKBN2C11XX