Pfizer to pursue bringing COVID-19 vaccine to India after import relaxation

 Pfizer Inc said on Tuesday it would work towards bringing the COVID-19 vaccine it developed with Germany’s BioNTech to India after the government eased import rules, after withdrawing its application in February.

“We have noted the recent announcement with regard to the regulatory pathway for global vaccines,” a Pfizer spokesperson told Reuters in an email.

“We remain committed to continuing our engagement with the government towards making the Pfizer and BioNTech vaccine available for use in the government’s immunisation program.”

https://www.reuters.com/article/us-health-coronavirus-india-pfizer/pfizer-to-pursue-bringing-covid-19-vaccine-to-india-after-import-relaxation-idUSKBN2C01WE

India, big vaccine exporter, now seeks imports as COVID cases soar

 India is to fast-track emergency approvals for COVID-19 vaccines that have been authorised by Western countries and Japan, paving the way for possible imports of Pfizer, Johnson & Johnson, and Moderna shots.

The move, which will drop the need for companies to do small, local safety trials for their vaccines before seeking emergency approval, follows the world’s biggest surge in cases in the country this month.

India has the biggest vaccine manufacturing capacity in the world and had exported tens of millions of doses before its own demand skyrocketed and led to a shortage in some states.

Its need for imports would be a blow to dozens of poor countries that had relied on the country to run their inoculation drives.

India’s health ministry said vaccines authorised by the World Health Organization or authorities in the United States, Europe, the United Kingdom and Japan “may be granted emergency use approval in India, mandating the requirement of post-approval parallel bridging clinical trial”.

“If any of these regulators have approved a vaccine, the vaccine is now ready to be brought into the country for use, manufacture and fill-and-finish,” Vinod Kumar Paul, a senior government health official, told a news conference.

“We hope and we invite the vaccine makers such as Pfizer, Moderna, Johnson & Johnson and others ... to be ready to come to India as early as possible.”

Pfizer said it would work towards bringing its vaccine to India after withdrawing its application in February.

India has administered more than 108 million doses, sold more than 54.6 million vaccine doses abroad and gifted more than 10 million to partner countries.

It is currently using the AstraZeneca shot and a homegrown vaccine for its own immunisation drive, and this week approved Russia’s Sputnik V shot for emergency use.

RALLIES, RELIGIOUS EVENTS

Since April 2, India has reported the world’s highest daily tallies of infections, exceeding 100,000 for the first time last week. It reported 161,736 cases on Tuesday, taking the total to 13.7 million. Deaths rose by 879 to 171,058.

The jump in infections, for which Health Minister Harsh Vardhan acknowledged here widespread failure to heed curbs on movement and social interaction, has prompted calls for the government to cancel huge public events.

But hundreds of thousands of devout Hindus are set to bathe in the Ganges river on Wednesday, the third key day of the weeks-long Kumbh Mela - or pitcher festival.

Nearly a million bathed in the Ganges on Monday in the belief that its waters would wash away their sins. More than 100 tested positive for COVID-19 in random testing of around 18,000 attendees, media said.

Similar concerns of a spike in cases were sparked by mass election rallies by Prime Minister Narendra Modi’s party and opposition groups during polls in four states and one federally run region.

At one rally in the eastern state of West Bengal, a key political prize, Home Minister Amit Shah posted Twitter pictures of meetings with crowds of supporters while unmasked.

DEADLY SPREAD

The second wave of infections, which began in India’s major cities, is increasingly spreading into the hinterland, where healthcare facilities are often rudimentary.

In Raipur, the capital of Chhattisgarh state known for its large tribal population, the main government hospital’s morgue was struggling to keep up, said joint director Dr Vineet Jain.

“All oxygenated and ICU beds are full in our set-up,” he told Reuters.

“Around 50 dead bodies are laying, we have a shortage of space. Some private hospitals do not have space to keep the dead bodies so they also send the bodies to us.”

India is currently reporting around double the daily cases of the United States and Brazil, the two other worst affected countries, though its daily death toll is lower.

India’s total infections rank after only the United States, having overtaken Brazil on Monday.

https://www.reuters.com/article/us-health-coronavirus-india/india-big-vaccine-exporter-now-seeks-imports-as-covid-cases-soar-idUSKBN2C00BX

U.S. pauses J&J COVID-19 vaccine over rare blood clots

 U.S. federal health agencies on Tuesday recommended pausing the use of Johnson & Johnson’s COVID-19 vaccine after six women under 50 given the shot developed rare blood clots, dealing a fresh setback to efforts to tackle the pandemic.

Following the news, Johnson & Johnson (J&J) said it was delaying the rollout of the vaccine to Europe, a week after regulators there said they were reviewing rare blood clots in four recipients of the shot in the United States.

The moves come after European regulators said earlier this month they had found a possible link between AstraZeneca’s COVID-19 vaccine and a similar rare blood clotting problem that led to a small number of deaths.

J&J’s single dose vaccine - most COVID-19 shots are delivered over two doses - and AstraZeneca’s low-cost vaccine are seen as vital tools in the fight against a pandemic that has claimed more than three million lives.

The White House said the pause would not have a “significant” impact on its plan to administer about three million shots per day and a total of 200 million shots before President Joe Biden’s 100th day in office.

The U.S. Food and Drug Administration (FDA) said one person had died from the rare blood clotting condition after taking the J&J vaccine and another was in a critical condition.

Immunology experts stressed the risk posed by the J&J vaccine appeared extremely low, and that the shot remained a valuable tool against the risks of COVID-19. However they acknowledged the need for health officials to proceed with caution to understand the best ways to mitigate any risk.

“Even if causally linked to the vaccine: 6 cases with about 7 million doses (lower than the risk of clots with oral contraceptives) is not something to panic about,” Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Security in Baltimore, said in an email.

“People are asking me if they should cancel their J&J vaccine appointments and I have told them not to but I know many will and this will stall progress in controlling the pandemic.”

FDA acting commissioner Janet Woodcock said it expected the pause to be a matter of days, and it was aimed at providing information to healthcare providers so that they can diagnose, treat and report such blood clots.

FDA official Peter Marks said that part of the reason for the pause was to warn doctors that administering the standard treatments for clots can cause tremendous harm, or be fatal.

‘LESS THAN ONE IN A MILLION’

Most of the available J&J vaccine has been used in the United States due to production issues that have limited the company’s supply. As of April 12, more than 6.8 million doses of the J&J vaccine had been administered in the United States, compared with more than 180 million shots combined of the Moderna and Pfizer/BioNTech shots.

U.S. health officials said during a press briefing there had been no similar blood clot cases reported among recipients of the Pfizer/BioNTech of Moderna vaccines.

An advisory committee to the U.S. Centers for Disease Control and Prevention (CDC) will meet on Wednesday to review the cases, and the FDA will review the analysis, the agencies said in a joint statement.

All six cases involved women between the ages of 18 and 48, and the symptoms occurred six to 13 days after vaccination.

In the cases, a type of blood clot called cerebral venous sinus thrombosis (CVST) was seen in combination with low levels of blood platelets (thrombocytopenia).

J&J said it was working closely with regulators and noted no clear causal relationship had been established between the cases and the COVID-19 vaccine made by its Janssen unit.

“Even if all of the cases were caused by the vaccine, the risk of less than one in a million would have to be set against the benefits of protection from COVID-19 disease; a disease which, in itself, causes clotting in many cases,” said Peter English, a retired consultant in communicable disease control and a vaccine expert.

‘ABUNDANCE OF CAUTION’

“The FDA recommendation to pause the administration of the Johnson and Johnson vaccine out of an abundance of caution makes sense in terms of the nature of the unusual and serious side effect not seen with the other vaccines,” said Dr. Robert Klugman at the UMass Memorial Medical Center in Massachusetts in an email.

The J&J and AstraZeneca vaccines both use an adenovirus vector - a harmless cold virus that instructs human cells to produce a protein found on the surface of the coronavirus, thereby spurring the immune system to prepare an arsenal against the COVID-19-causing virus.

Among leading global COVID-19 vaccine developers, China’s CanSino Biological and Russia’s Gamaleya Institute with its Sputnik V vaccine are also relying on this approach. The Pfizer/BioNtech and Moderna vaccines use mRNA technology.

The rollout of J&J’s vaccine has been slowed by issues at production plants.

The company has supplied the United States with at least 20 million doses but is behind schedule on its deliveries. Problems at a Baltimore, Maryland plant run by outside contractor Emergent BioSolutions forced the companies to trash a batch of vaccine substance.

J&J only began delivering its COVID-19 vaccine to European Union countries this week. It has committed to delivering 55 million doses to the bloc by the end of June and another 120 million in the third quarter.

J&J has been doing vaccinations in South Africa to study the effects on health workers, and had vaccinated just under 300,000 people there as of Monday, according to data from the country’s health department. J&J recently struck a deal with the African Union for up to 400 million doses.

Europe’s drugs regulator continues to recommend the use of AstraZeneca’s COVID-19 vaccine, saying the benefits outweigh the risks. Several EU countries, however, have limited its use to certain age groups.

https://www.reuters.com/article/us-health-coronavirus-johnson-johnson-va/u-s-pauses-jj-covid-19-vaccine-over-rare-blood-clots-idUSKBN2C01BC

Novavax: Supply shortages delay full-speed production of its COVID-19 vaccine

 Novavax Inc has pushed back the timeline for hitting its production target of 150 million COVID-19 vaccine doses per month until the third quarter due to supply shortages including bags used to grow cells, a company spokeswoman told Reuters.

Novavax executives had previously said full-scale vaccine production could be achieved by mid-year. The company told Reuters in January it expected to reach full production capacity by May or June.

“We said during our earnings call that we expect all capacity being online by around mid-year. We’re continuing to refine that timing as we get closer, which now leads us to think we’re online/at full capacity by Q3,” Novavax communications director Amy Speak said by email on Monday.

“There are some supply shortages that come and go that have contributed to the revision in timing,” she added. “These have included things like the bioreactor bags and filters.”

Novavax could receive UK regulatory authorization for its vaccine as early as this month after releasing impressive UK trial data. It anticipates clearance in the United States could come as early as May after soon-to-be released data from its U.S. vaccine trial are reviewed by regulators.

The Maryland-based company is one of several COVID-19 vaccine makers that have had to push back production timelines due to industrywide shortages of raw materials and difficulties getting plants up and running.

Reuters reported last month that Novavax had delayed a planned deal to ship at least 100 million doses of its two-shot vaccine to the European Union, in part because of supply challenges.

In a Saturday interview with the Guardian, Novavax Chief Executive Stan Erck said the company has faced difficulties sourcing key production materials including single-use bags used to grow vaccine cells.

“Single-use bags are facing critical shortages and delays,” said Mark Womack, chief business officer of AGC Biologics, a contract manufacturer that is producing materials used in Novavax’s vaccine.

Data released in March from the UK trial showed the vaccine to be highly effective against the original strain of the novel coronavirus as well as the more contagious and deadly variant first discovered in Britain and now rampant in Europe and the United States. The data also suggests the shot provides some protection against a highly concerning variant that emerged in South Africa, which some drugmakers have said may require a booster shot to address.

https://www.reuters.com/article/us-health-coronavirus-novavax/novavax-says-supply-shortages-delaying-full-speed-production-of-its-covid-19-vaccine-idUSKBN2C013Z

AACR: BeiGene details Novartis-partnered PD-1's first global pivotal win in lung cancer

 BeiGene’s PD-1 inhibitor tislelizumab has several indications under its belt in China, but its global rollout, now wrapped up in a collaboration with Novartis, has yet to kick off. But things are headed in that direction: The drug has detailed its first global pivotal trial win, teeing up a potential filing outside its home country.

Compared with commonly used chemotherapy docetaxel, tislelizumab monotherapy cut the risk of death by 36% in patients with non-small cell lung cancer (NSCLC) that had progressed on one to two lines of systemic therapy, BeiGene unveiled at the American Association for Cancer Research annual meeting.

The reduction was for all trial participants. Those on the PD-1 drug lived a median 17.2 months, versus 11.9 months for the chemo group. As expected, the drug’s effect was more pronounced in patients with high expression levels of PD-L1, as the death risk reduction amounted to 48% in that group.

BeiGene and Novartis now expect the first ex-China regulatory filings for tislelizumab to be in non-small cell lung cancer and esophageal squamous cell carcinoma before the end of 2021, a Novartis media aide said via email. An application for the second-line NSCLC use was accepted for review by Chinese authorities last month.

But an FDA green light in previously treated NSCLC may be important to tislelizumab more as a symbolic milestone than from a perspective of market opportunity in that specific indication. Currently, the standard of care for previously untreated patients is the combination of Merck & Co.’s PD-1 inhibitor Keytruda and chemotherapy. Tislelizumab’s current Rationale 303 trial excluded patients who had previously gotten PD-1/L1 cancer immunotherapies.

As Keytruda has established a strong presence in front-line use, the relevant competitor for tislelizumab in second-line NSCLC is Bristol Myers Squibb’s Opdivo. There isn’t an Opdivo study that’s equivalent to Rationale 303 for comparison, but the BMS drug’s second-line nod for squamous and nonsquamous diseases were based on the CheckMate-017 and CheckMate-057 trials, respectively, both of which pitted Opdivo against docetaxel.

In those two studies, Opdivo showed it could reduce the risk of death by 27% in previously treated patients with nonsquamous NSCLC and by 41% among second-line patients with the squamous subtype. The Opdivo trials and the tislelizumab trial can’t be directly compared, as they enrolled different populations; for example, Rationale 303 didn’t allow patients with EGFR or ALK mutations, while CheckMate-057 did. Rationale 303 also didn’t enroll any patients in the U.S.

Besides previously treated NSCLC, BeiGene recently also said a second global phase 3 trial, Rationale 302, showed tislelizumab topped chemo at helping previously treated esophageal squamous cell carcinoma patients live longer. Details from that win remain under wraps. 

An esophageal cancer OK would also set tislelizumab on a collision course with Keytruda and Opdivo, both of which are allowed in the second-line setting. Keytruda just broke into front-line treatment, and Opdivo—either in combination with chemotherapy or with BMS’ CTLA4 inhibitor Yervoy—is eyeing the same setting.

Without a clear efficacy or safety edge, Novartis and BeiGene will have a hard time stealing share from those two established PD-1 players. One front on which tislelizumab can compete with those Western-made checkpoint inhibitors? Pricing, as BeiGene management and pharma watchers have suggested.

Currently in China, tislelizumab’s annual cost for China’s national reimbursement comes at roughly CNY 74,000 ($11,300). Opdivo, without national coverage, costs roughly CNY 110,600 ($16,900) after patient assistance.

https://www.fiercepharma.com/marketing/aacr-beigene-details-novartis-partnered-pd-1-s-first-global-trial-win-lung-cancer-should

Cipla doubles remdesivir production to meet 'unprecedented' demand

  India’s Cipla Ltd has doubled production of COVID-19 medication remdesivir to help meet “unprecedented demand” as the country battles a massive second wave of infections, the drugmaker said on Tuesday.

India has overtaken Brazil as the world’s second-worst coronavirus-hit country after the United States, having administered about 107 million vaccine doses among a population of 1.4 billion.

On Sunday, the country banned the export of anti-viral drug remdesivir and its active pharmaceutical ingredients to deal with crippling shortages of the medication in many parts.

“We have scaled up the production of remdesivir by 2x from the last wave of the pandemic,” Cipla said in a statement to Reuters. “Given the unprecedented demand for the drug, we have now further ramped up our capacities through our network.”

The company is working with authorities to restrict remdesivir supply just to hospitals and places with a high burden of severe COVID-19 cases, it added.

Just two months ago, Cipla had projected falling demand for remdesivir in India as coronavirus infections were on a steady decline.

The World Health Organization in November issued a conditional recommendation against the use of remdesivir in hospitalised patients, saying there was no evidence that the drug improved survival and other outcomes. Still, many countries, including India, have continued its use.

Cipla, one of India’s oldest and largest drug manufacturers, has a deal to make and supply U.S.-based Gilead’s remdesivir in more than 100 countries. Several other Indian drug producers also have similar agreements.

Cipla also warned that it was facing a shortage of tocilizumab, an arthritis drug developed by Roche that has been shown in trials to reduce the risk of death in patients with severe COVID-19.

“We expect intermittent supplies (of tocilizumab) as demand outstrips supply,” Cipla said.

https://www.reuters.com/article/us-health-coronavirus-india-cipla/indias-cipla-doubles-remdesivir-production-to-meet-unprecedented-demand-idUSKBN2C00UP

China's mRNA COVID-19 vaccine may start late-stage trial in May

 China’s locally developed COVID-19 vaccine candidate that uses messenger RNA (mRNA) technology could start late-stage clinical trial overseas as early as next month, official media said on Tuesday.

ARCoV, the China-developed mRNA vaccine candidate that is furthest along the clinical trial process, may get overseas approval to conduct Phase III clinical trial by as early as end-April, China National Radio said in an article on its website.

China has approved four locally developed coronavirus vaccines for general public use and a fifth for smaller-scale emergency use but none of them uses the mRNA platform. The country has administered more than 170 million vaccinations, the second-highest number of doses in the world after the United States.

The mRNA technology is used by rival shots developed by Pfizer Inc and its partner BioNTech, as well as by Moderna Inc. It contains instructions for human cells to produce proteins that mimic part of the coronavirus.

ARCoV is being jointly developed by the Academy of Military Science (AMS), Suzhou Abogen Biosciences and Walvax Biotechnology. Overseas clinical trials could formally begin in May, and South America could be a “first option” as a trial location, the report said, citing an interview with Ying Bo, founder of Suzhou Abogen Biosciences.

Ying said early stage trial data has shown that its vaccine is “fully comparable with two overseas mRNA vaccines,” without elaborating on the specific readings.

A Phase II clinical trial of ARCoV is underway in China and has completed injecting participants, Qin Chengfeng, an AMS researcher leading the vaccine project, said on Sunday during a presentation at a vaccine event. Results for the trial have not yet been made public.

Another COVID-19 vaccine candidate using mRNA technology being jointly developed by Chinese firm Stemirna Therapeutics and Tibet Rhodiola Pharma has also obtained approval to begin a clinical trial, Rhodiola said in January.

https://www.reuters.com/article/us-health-coronavirus-vaccine-china/chinas-mrna-covid-19-vaccine-may-start-late-stage-trial-in-may-state-media-idUSKBN2C00Y3