Covid-19 booster shots take centre stage

 Astrazeneca’s swift advancement into pivotal trials of AZD2816, a booster vaccine optimised for the Covid-19 Beta variant, will have softened the blow of a US delay to the group’s original vaccine, Vaxzevria. Today Astra confirmed that Vaxzevria’s US regulatory path would comprise a full BLA filing rather than a much quicker emergency use authorisation.

Still, many had long suspected that pursuing a BLA was inevitable, and perhaps the bigger question now is when Astra might start making a profit on Vaxzevria. This is also relevant if next-generation vaccines gain importance – something echoed by Pfizer, which pressed its own case for boosters during its earnings call yesterday.

Astra’s commitment to provide Covid-19 vaccines at cost while the current pandemic persists marks one difference between the two companies. While yesterday Pfizer booked $7.8bn of second-quarter Comirnaty sales, fuelling an earnings uplift, today Astra reported $1.1bn of first-half Vaxzevria revenue, at zero profit.

Presumably the UK group’s commitment will extend to AZD2816, but a switch to booster shots might be one indication that the initial pandemic, at least in many western countries, is over. On a call today Astra’s chief executive, Pascal Soriot, offered no specific guidance, and said his goal was to deliver on doses ordered so far, all at cost.

Booster trial

But focus will fall increasingly on a phase 2/3 study of AZD2816. This has two parts, the first in subjects already vaccinated with two doses of Vaxzevria or an mRNA vaccine, giving subjects a booster dose of either Vaxzevria or AZD2816, and is expected to yield data in the current quarter, leading to UK filing by the year end.

The second part is designed for rest-of-world approval, and is in unvaccinated individuals, testing two doses of Vaxzevria or AZD2816. Data are expected by the end of the fourth quarter. Interestingly, this booster programme appears to be an answer to a waning efficacy problem that Astra does not yet accept it has.

Not so Pfizer, which yesterday showed waning neutralising antibody level data eight months after the second Comirnaty dose, highlighting how levels increased again after a third shot.

Source: Pfizer's second-quarter earnings presentation.

The obvious question, of course, is whether declining antibody levels correlate with decreasing vaccine efficacy. Pfizer said it was now getting reports of breakthrough infections in countries other than Israel, one of the first to launch its vaccination programme.

This stance was further strengthened by long-term data from Comirnaty’s phase 3 trial, published as a preprint yesterday, showing vaccine efficacy slipping to 84% at six months, though efficacy against severe disease was 97%.

For its part, however, Astra said antibody levels were just one part of the immune response; another was T cells. “Adeno vector vaccines tend to stimulate large production of T cells, and it’s quite possible that these will provide long-lasting protection,” said Mr Soriot, though he too accepted some loss of antibodies over time after Vaxzevria.

If boosters do become the norm, the next question is whether they might be a one off or be given periodically. Pfizer’s chief scientific officer, Mikael Dolsten, said he “would not be surprised” if a Covid-19 shot would be needed at regular intervals. This could be either annual or based on a diagnostic, he added.

EUA

Pfizer plans to ask for emergency use authorisation (EUA) of a booster by August, when it will also start clinical trials of a Delta-specific vaccine. A separate issue is that the US Centers for Disease Control and FDA have initially come out against Covid-19 boosters.

For Astra, before AZD2816 becomes reality Vaxzevria probably needs to make it across the US finish line. The initial vaccine has suffered repeated delays, and work is now under way to gather sufficient data for a pre-BLA meeting, and to start a rolling BLA filing by the year end.

“The reason it’s taking a long time is because the FDA is requesting an awful lot of information,” said Mene Pangalos, Astra’s head of biopharmaceuticals R&D. This apparently includes UK, Brazil, Africa and US studies, in addition to real-world data.

It is also possible that full BLA approval will boost Astra’s chances of raising Vaxzevria’s price. Mr Soriot stressed that Astra does not intend to make a “large profit”, but said that “at some point in the future we will move to an affordable price. We can’t be at no profit forever.”

https://www.evaluate.com/vantage/articles/news/pricing/covid-19-booster-shots-take-centre-stage

Insulin goes generic

 Viatris’s Semglee was first approved last year, but its new interchangeable label means that it can be substituted for the reference product, Sanofi’s long-acting Lantus, at US pharmacies, like a generic. The FDA believes that this direct competition will cut prices; the amount US patients pay for insulin products has surged over the past few years. According to GoodRx, when bought without insurance a vial of Lantus costs around $190, versus around $110 for Semglee, though this pricing does not appear to take account of the new approval. But when a patient has insurance or Medicare coverage the calculation can become more complicated. In Sanofi's 2021 pricing report the company said that since 2012 the amount it received for Lantus had fallen 45% – but the average out-of-pocket cost for Lantus patients with commercial insurance and Medicare had risen 82%. Availability of a cheaper generic might simply mean that patients pay a similar amount and insurers pocket the difference. Perhaps more generics might help. Viatris will have a year on the market with Semglee before the FDA can approve another interchangeable biosimilar, but several non-interchangeable ones are available around the world, and some might eventually attain this additional label. 

Biosimilar versions of Sanofi's Lantus (insulin glargine)
Company	Product	Status
Viatris	Semglee, Basalog	Launched in India in 2009, Japan in 2016, S Korea & UK in 2018 and Australia in 2019; approved in EU in 2018; approved in the US in 2020 and as interchangeable in 2021
Lilly/Boehringer Ingelheim	Basaglar, Abasaglar	Launched in South Korea in 2017; approved in EU & US in 2014 and in Australia & Japan in 2015
Samsung Bioepis	Lusduna	Approved in Europe in 2017; tentative US approval for follow-on biological granted in 2017
Gan & Lee	Basalin	Launched in China in 2005
Wockhardt	Glaritus	Launched in India in 2009
Kalbe Pharma	Ezelin	Launched in Indonesia in 2017
GC Pharma	Glarzia	Launched in S Korea in 2018
Source: the Generics and Biosimilar Initiative.  https://www.evaluate.com/vantage/articles/news/snippets/insulin-goes-generic

FDA authorizes Lilly’s baricitinib as Covid-19 treatment

 The U.S. Food and Drug Administration has revised its emergency use authorization (EUA) for Lilly’s baricitinib and authorized it as a Covid-19 treatment.

The U.S. FDA has authorized Lilly’s baricitinib as monotherapy for Covid-19.
Baricitinib, developed by Eli Lilly as a treatment for rheumatoid arthritis, is sold under the brand name Olumiant. The FDA granted EUA for the combination of remdesivir and baricitinib as a treatment for Covid-19 in November.

Under the revised authorization, U.S. medical institutions will use the treatment on hospitalized adults and pediatric patients two years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

“This revision to the EUA for baricitinib was supported by data from a clinical trial of hospitalized patients with Covid-19, where baricitinib showed a reduction in the proportion of patients who died through 28 days of follow-up compared to patients treated with the standard of care for COVID-19 alone,” the FDA said. “This study did not require hospitals to administer a combination of baricitinib and remdesivir, and most of the patients did not receive remdesivir.”

The study provided information previously unavailable to the agency at the time of the original authorization, the agency added.

The FDA added that while the revised EUA no longer requires hospitals to use baricitinib in combination with remdesivir, the agency’s letter of authorization notes that the trial supporting this revision did not raise questions about the safety or efficacy of baricitinib when used in combination with remdesivir for the treatment of patients hospitalized due to Covid-19 requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECMO.

“Therefore, the use of baricitinib in combination with remdesivir is not contraindicated under the terms and conditions of this authorization,” the FDA said. “A contraindication describes when the use of a product is not appropriate.”

https://www.koreabiomed.com/news/articleView.html?idxno=11781

Cassava Sciences Announces Positive Cognition Data With Simufilam in Alzheimer’s

 

• Simufilam Significantly Improves Cognition in Patients with Alzheimer’s in Interim Analysis of Open-label Study at 9 Months
  
  

• Cognition Improved 3.0 Points on ADAS-Cog at 9 Months (p<0.001)
  
  

• Cognitive Improvements Track with Biomarker Improvements
  
  

• No Behavior Disorders in Over 50% of Patients
  
  

• No Safety Issues

https://finance.yahoo.com/news/cassava-sciences-announces-positive-cognition-135300621.html

J&J Says U.S. FDA Agrees to Extend Shelf Life of Its COVID-19 Vaccine

 The U.S. Food & Drug Administration extended the shelf life for Johnson & Johnson's single-shot COVID-19 vaccine to six months from four-and-a-half months, the company said late Wednesday.

The FDA's decision is based on data from ongoing studies, which showed the vaccine is stable at six months when refrigerated at 2 to 8 degrees Celsius (36–46 degrees Fahrenheit), the drugmaker said.

In a letter to the company, the FDA said it had completed the review of data provided by J&J, and based on the information submitted, it concurs with the extension. (https://bit.ly/3zRuTMB)

The agency also said the extension was applicable to batches that might have expired prior to the issuance of the letter provided they were stored at the recommended temperature.

https://www.usnews.com/news/top-news/articles/2021-07-28/j-j-says-us-fda-agrees-to-extend-shelf-life-of-its-covid-19-vaccine

U.S. expected to keep border expulsions policy as Delta variant cases surge

 The United States is expected to delay a partial rollback of a controversial migrant expulsion policy, according to three people familiar with the matter, citing fears related to the fast-spreading Delta variant of the coronavirus.

The administration of President Joe Biden had planned to exempt migrant families arriving at the U.S.-Mexico border from the expulsion policy by July 31, while continuing to keep it for individuals, sources familiar with the discussions told Reuters earlier this month.

The partial rollback of the Title 42 policy was delayed because the Biden administration "put the brakes on it" due to concerns over the highly transmissible COVID-19 Delta variant and the rising number of infections in Mexico, one of the people said.

It is now unclear when the order could be lifted for families or in its entirety.

Biden, a Democrat, has been under intense pressure from human rights groups, some fellow Democrats, migrant advocacy groups and United Nations refugee officials to end the Trump-era policy they say leads to thousands of expelled migrants facing kidnappings and other violence in northern Mexico.

Biden has kept Title 42 in place as border arrests have risen to their highest monthly levels in 20 years. Since he took office in January, migrants have been expelled under Title 42 more than 500,000 times, although many of those include repeat border crossers.

"It will remain in place as long as that is the guidance from our health and medical experts," White House Press Secretary Jen Psaki said during a briefing on Monday, referring to the U.S. Centers for Disease Control and Prevention (CDC). She added that the administration had never publicly set a date for ending it.

U.S. coronavirus cases have been rising due to the Delta variant, which emerged in India but has quickly spread and now accounts for more than 80% of U.S. coronavirus cases.

Biden risks alienating pro-migrant allies and members of his own party if he continues to keep Title 42, which was one of former President Donald Trump's most restrictive immigration policies.

The administration already faces a legal challenge over the family expulsions led by the American Civil Liberties Union (ACLU).

The ACLU agreed in February to pause litigation so that the parties could attempt to resolve or narrow the dispute but will decide by Monday whether to resume the legal challenge, according to Lee Gelernt, deputy director of the ACLU's immigrants’ rights project.

"(Title 42) has caused enormous hardship and could never be justified on public health grounds," Gelernt said in an emailed statement to Reuters. "By August 2 we will alert the court whether it is time for us to end negotiations and resume the litigation, which we always said we would do if an end to Title 42 is not in sight."

Representative Judy Chu, a Democrat whose congressional district includes part of Los Angeles, said the Biden administration did not have an adequate rationale for expelling asylum seekers while allowing hundreds of thousands of legal travelers and other migrants caught at the border to enter the United States.

Chu joined a group of more than 60 Democratic lawmakers who earlier this year urged the Biden administration to end the policy.

"They're just indiscriminately rejecting people and sending them back," she said in an interview.

Still, the Biden administration exempted unaccompanied children from the policy in February and has been phasing it out for migrant families arriving at the southern border.

In June, 84% of the roughly 50,000 migrant family members caught at the southern border were allowed into the United States to pursue their cases.

The White House, CDC and Department of Homeland Security did not respond to requests for comment.

CNN first reported last week on a possible delay to the rollback of the order for families.

CONSEQUENCES OF THE DELAY

Thousands of migrants have been granted humanitarian exceptions to the border policy under an informal program managed on the ground by a consortium of non-profit organizations who help to identify those most vulnerable.

The program has mitigated the impact of Title 42, but a number of the non-profits have either ended their participation in it or are planning to in the coming weeks, compounding the impact of the delay in rolling back Title 42.

"We have made a commitment to do this until the end of August," said Rachel Levitan, vice president for international programs with HIAS, a refugee organization formerly known as the Hebrew Immigrant Aid Society. "That is the end of the line for us."

While Biden is under pressure to end Title 42, he is also being pressed by Republicans and some Democrats in border states to keep it in place.

Migrant crossings typically taper off in the hot summer months, but arrests at the southern border rose in June to the highest level since April 2000. The tally in July is expected to be similar or even higher, according to two border patrol officials who spoke on the condition of anonymity.

Representative Henry Cuellar, a Democrat who represents a border district in south Texas, is urging the Biden administration to keep the policy and step up immigration enforcement to discourage people from crossing.

"They're afraid to show people being deported because they don't want to offend the left," Cuellar said. "I think they put so much emphasis on the immigration activists. They need to start paying attention to the border communities."

https://news.yahoo.com/u-expected-keep-border-expulsions-102231415.html

Biden to ask federal workers to get vaccinated against COVID-19 or face testing

 US President Joe Biden on Thursday (Jul 28) is expected to announce that about two million civilian federal workers will need to be vaccinated against the coronavirus or face testing, social distancing, mask requirements and limits on travel, according to a source familiar with the matter.

Biden, who will deliver remarks on COVID-19 at the White House at 4pm on Thursday (Friday, 4am, Singapore time), will not mandate vaccines for federal employees and those who decide against getting a vaccine will not be at risk of being fired, the source said.

The plan is similar to what some states and New York City have announced, the source added. For example, New York Governor Andrew Cuomo said on Wednesday that state employees will be required to be vaccinated or get tested weekly.

On Tuesday, Biden said his administration was considering the requirement for federal employees.

Numerous US agencies on Wednesday mandated masks at federal buildings in COVID-19 hot spots in line with instructions issued by the White House Office of Management and Budget (OMB), according to an OMB email seen by Reuters.

The White House also said masks are required indoors in federal buildings for all employees and visitors, whether or not vaccinated, in those areas experiencing sharp increases in infections.

On Wednesday, the Centers for Disease Control and Prevention (CDC) said nearly 67 per cent of US counties were at substantial or high transmission rates, up from 63.4 per cent on Tuesday.

The federal government is racing to contain the pandemic in the hope of avoiding future nationwide shutdowns, as the virulent Delta variant of the coronavirus blazes through parts of the United States and immunisations lag.

Some organised labour groups such as the American Postal Workers Union (APWU) said it opposes a vaccine mandate for federal employees and expressed concern about Biden's expected announcement.

"While the APWU leadership continues to encourage postal workers to voluntarily get vaccinated, it is not the role of the federal government to mandate vaccinations for the employees we represent," the group said in a statement.

Others such as AFL-CIO President Richard Trumka told C-SPAN that the union supports vaccine mandates.

"If you come back in and you are not vaccinated, everybody in that workplace is jeopardised," Trumka said.

https://www.channelnewsasia.com/news/world/biden-federal-workers-vaccine-covid-19-testing-15324550