Gilead, Merck collaborate to develop long-acting HIV treatment

  Gilead Sciences Inc has entered into an agreement with Merck & Co Inc to develop a long-acting HIV treatment, the drug makers said on Monday.

Gilead will combine its experimental drug lenacapavir, and Merck’s islatravir into a two-drug regimen that would allow for less frequent, oral or injectable dosing for HIV patients.

Gilead and Merck will share global development and commercialization costs 60% and 40%, respectively. The companies will have an equal share in sales of the therapy until the revenue crosses certain milestones.

The companies expect to begin testing in people an oral version of the combination during the second half of this year.

https://www.reuters.com/article/us-gilead-sciences-merck-co-hiv/gilead-merck-collaborate-to-develop-long-acting-hiv-treatment-idUSKBN2B716P

Moderna testing new COVID-19 vaccine as potential booster shot

  Moderna Inc said on Monday it had dosed the first patients in an early-stage study of a new COVID-19 vaccine candidate for its potential evaluation as a booster shot.

The company said its new candidate, mRNA-1283, could potentially be stored in refrigerators instead of freezers, making it easier to distribute, especially in developing countries.

The early-stage study will assess the safety and immunogenicity of mRNA-1283 at three dose levels, and will be given to healthy adults either as a single dose or in two doses 28 days apart, the company said.

Last week, Moderna began dosing the first participants in a study testing its COVID-19 booster vaccine candidates.

https://www.reuters.com/article/us-health-coronavirus-moderna/moderna-testing-new-covid-19-vaccine-as-potential-booster-shot-idUSKBN2B71OE

Money, talent flowing into mRNA sector after COVID-19 success

 The success of COVID-19 vaccines based on messenger RNA (mRNA) is smoothing the way for using the novel technology not only in other vaccines, but possibly as treatments for cystic fibrosis, cancer and other hard-to-treat diseases.

Scientists say mRNA has the potential to target diseases that cannot be reached by conventional drugs.

U.S. emergency authorization of the vaccines - one from Moderna Inc and another from partners Pfizer Inc and BioNTech SE – and their gene-based manufacturing processes has shown that the Food and Drug Administration is open to broader use of the previously unproven technology, according to interviews with eight top experts in the field of mRNA.

Billions of dollars in capital have flowed into mRNA-focused companies based on these raised expectations – hundreds of millions in the last few months alone. And with FDA acceptance, the field is attracting top scientific talent, experts said.

“There is more attention and focus on mRNA now that it has proven to be a technology that works,” said Glenn Hunzinger, U.S. pharmaceutical and life sciences leader at consulting firm PricewaterhouseCoopers.

Regulatory authorization of the vaccines “accelerates the process” for other mRNA therapies, providing real-world evidence that it is possible to secure fragile mRNA components during manufacturing and distribution, said Josh Kellar, co-lead of Boston Consulting Group’s COVID-19 team.

The technology is often likened to the operating system on a computer, allowing drugmakers to alter their target by inserting new genetic code into a manufactured form of mRNA, a natural chemical messenger that instructs the body to produce specific proteins.

Its advantage in vaccines is versatility and speed compared to standard technology requiring long lead times to produce and purify proteins and create a vaccine.

TREATMENTS REACH HUMAN TESTING

In 2020, given the urgent need created by the coronavirus pandemic, more than $5.2 billion was invested in companies engaged in developing mRNA vaccines and therapeutics - up from $596 million in 2019, according to India-based research firm Roots Analysis.

In just the last three months, mRNA company CureVac NV raised $518 million, Arcturus Therapeutics Holding raised $150 million and Gilead Sciences Inc agreed to a therapeutic HIV vaccine deal worth up to $785 million to mRNA company Gritstone Oncology.

Over 150 mRNA vaccines and therapeutics are in development globally, Roots Analysis said. Most are still in early animal testing, but more than 30 have reached human testing.

mRNA can be very difficult to work with, making future successes with treatments uncertain.

Instructions from mRNA are fleeting and non-specific about where in the body it goes, which works well when directing cells to make a harmless fragment of the coronavirus to trigger an immune response. It is more difficult to send those orders to a specific tissue, like the lungs or heart muscle, which requires different delivery methods or encapsulation to protect the fragile mRNA molecule.

Most of last year’s funding went to COVID-19 projects but enabled companies to also push forward with other disease categories.

Moderna, for instance, is working on treatments for heart disease, cancer, and rare diseases. Its most advanced non-COVID program is a vaccine for cytomegalovirus, the leading cause of birth defects in the United States.

Translate Bio Inc may be the first to market with an mRNA treatment if its inhaled drug for cystic fibrosis is shown to succeed at delivering instructions to make a protein known as CFTR to the lungs, according to Chief Executive Ron Renaud.

The company expects to have interim results from a mid-stage trial in the second quarter of this year. If safety and efficacy results are encouraging, it would conduct a larger trial and then potentially apply for U.S. approval.

People with cystic fibrosis, a life-shortening lung disease, have mutations in the CFTR gene that cause the protein to malfunction or not be made at all, leading to a buildup of thick mucus, which causes lung infections and other serious health complications.

“Most drugs treat the downstream effects of disease ... mRNA is in the business of replacing what’s missing,” said Joe Payne, CEO of Arcturus, which is working to develop mRNA vaccines for COVID-19 and influenza, as well as medicines for liver disease and cystic fibrosis.

Dr. Drew Weissman, professor of infectious diseases at the University of Pennsylvania’s Perelman School of Medicine, is one of the two scientists credited with a groundbreaking 2005 discovery of how to alter the molecular structure of mRNA to keep it stable enough to get past the body’s defenses.

In the past nine months, Weissman said 20 companies working in the field of mRNA have asked him to join their boards of directors, and the number of labs asking to collaborate with Penn on mRNA work has nearly tripled.

As fields like cell therapy start to mature, scientists angling for cutting-edge jobs are reaching out to mRNA companies, said Jacob Becraft, CEO at Strand Therapeutics, which is working on technology to control the activity of mRNA therapies.

“A lot of those people are inbounding to my inbox,” he said.

https://www.reuters.com/article/us-health-coronavirus-mrna/focus-money-talent-flowing-into-mrna-sector-after-covid-19-success-idUSKBN2B713D

Are regular booster vaccines the future in battle with COVID-19 virus?

 Regular booster vaccines against the novel coronavirus will be needed because of mutations that make it more transmissible and better able to evade human immunity, the head of Britain’s effort to sequence the virus’s genomes told Reuters.

The novel coronavirus, which has killed 2.65 million people globally since it emerged in China in late 2019, mutates around once every two weeks, slower than influenza or HIV, but enough to require tweaks to vaccines.

Sharon Peacock, who heads COVID-19 Genomics UK (COG-UK) which has sequenced half of all the novel coronavirus genomes so far mapped globally, said international cooperation was needed in the “cat and mouse” battle with the virus

“We have to appreciate that we were always going to have to have booster doses; immunity to coronavirus doesn’t last forever,” Peacock told Reuters at the non-profit Wellcome Sanger Institute’s 55-acre campus outside Cambridge.

“We already are tweaking the vaccines to deal with what the virus is doing in terms of evolution - so there are variants arising that have a combination of increased transmissibility and an ability to partially evade our immune response,” she said.

Peacock said she was confident regular booster shots - such as for influenza - would be needed to deal with future variants but that the speed of vaccine innovation meant those shots could be developed at pace and rolled out to the population.

COG-UK was set up by Peacock, a professor at Cambridge, exactly a year ago with the help of the British’s government’s chief scientific adviser, Patrick Vallance, as the virus spread across the globe to Britain.

The consortium of public health and academic institutions is now the world’s deepest pool of knowledge about the virus’s genetics: At sites across Britain, it has sequenced 346,713 genomes of the virus out of a global effort of around 709,000 genomes.

On the intellectual frontline at the Wellcome Sanger Institute, hundreds of scientists - many with PhDs, many working on a voluntary basis and some listening to heavy metal or electronic beats - work seven days a week to map and then search the virus’s growing family tree for patterns of concern.

Wellcome Sanger Institute has sequenced over half of the UK total sequenced genomes of the virus after processing 19 million samples from PCR tests in a year. COG-UK is sequencing around 30,000 genomes per week - more than the UK used to do in a year.

MUTATION LEADERBOARD

Three main coronavirus variants - which were first identified in Britain (known as B.1.1.7), Brazil (known as P1)and South Africa (known as B.1.351) - are under particular scrutiny.

Peacock said she was most worried about B.1.351.

“It is more transmissible, but it also has a change in a gene mutation, which we refer to as E484K, which is associated with reduced immunity - so our immunity is reduced against that virus,” Peacock said.

With 120 million cases of COVID-19 around the world, it is getting hard to keep track of all the alphabet soup of variants, so Peacock’s teams are thinking in terms of “constellations of mutations.”

“So a constellation of mutations would be like a leaderboard if you like - which mutations in the genome that we’re particularly concerned about, the E484K is must be one of the top of the leaderboard,” she said.

“So we’re developing our thinking around that leaderboard to think, regardless of the background and lineage, about what mutations or constellation of mutations are going to be important biologically and different combinations that may have slightly different biological effects.”

Peacock, though, warned of humility in the face of a virus that has brought so much death and economic destruction.

“One of the things that the virus has taught me is that I can be wrong quite regularly - I have to be quite humble in the face of a virus that we know very little about still,” she said.

“There may be a variant out there that we haven’t even discovered yet.”

There will, though, be future pandemics.

“I think its inevitable that we will have another virus emerge that is of concern. What I hope is that having learned what we have in this global pandemic, that we will be better prepared to detect it and contain it.”

https://www.reuters.com/article/us-health-coronavirus-britain-peacock-ex/exclusive-regular-booster-vaccines-are-the-future-in-battle-with-covid-19-virus-expert-says-idUSKBN2B70V2

EU considers getting a vaccine boost from Russia's Sputnik

 Publicly, the European Union has dismissed Russia’s global coronavirus vaccine supply campaign as a propaganda stunt by an undesirable regime.

Behind the scenes, the bloc is turning to Moscow’s Sputnik V shot as it tries to get its stuttering efforts to vaccinate its 450 million people back on track, EU diplomatic and official sources told Reuters.

An EU official who negotiates with vaccine makers on behalf of the bloc told Reuters that EU governments were considering launching talks with Sputnik V developers and it would take requests from four EU states to start the process.

Hungary and Slovakia have already bought the Russian shot, the Czech Republic is interested, and the EU official said Italy was considering using the country’s biggest vaccine-producing bioreactor at a ReiThera plant near Rome to make Sputnik V.

Brussels has been criticised for the bloc’s slow vaccine roll-out at a time when former member Britain is easing restrictions as its inoculation programme gathers pace. Italy is intensifying lockdowns, hospitals in the Paris region are close to being overloaded and Germany has warned of a third wave.

The EU has signed deals with six Western vaccine makers and launched talks with two more. It has approved four vaccines so far but production glitches have slowed its inoculation campaign and some member states are seeking their own solutions.

If Sputnik V were to join the EU’s vaccine arsenal, it would be a diplomatic triumph for Russia, whose trade with the bloc has been hamstrung for years by sanctions over its annexation of Crimea and its intervention in eastern Ukraine.

It would also risk dividing the bloc between those states dead set against giving Moscow any kind of win and those in favour of showing that Brussels can cooperate with the Kremlin.

‘LESS DESIRABLE’

A second EU official said the ReiThera plant was mentioned by Italian officials at a meeting as a possible site for producing COVID-19 vaccines made by companies other than the Italian biotech firm.

ReiThera, which is 30% owned by the state and is developing its own COVID-19 shot, declined to comment.

A spokeswoman for Italy’s industry ministry declined to comment on talks about the possible use of ReiThera’s plant to make Sputnik V. She said: “We will produce all authorised vaccines wherever possible.”

A spokesman for the European Commission, which coordinates talks with vaccine makers, said the EU was not required to launch talks with Sputnik V developers, even if the bloc’s drug regulator approves the vaccine.

It was not clear whether states that have ordered Sputnik V in bilateral deals would be interested in joint EU procurement. Spokespeople for the governments in the Czech Republic, Hungary and Slovakia did not respond to requests for comment.

Negotiations with vaccine makers have typically lasted months before supply deals were agreed and the EU official said no decision had yet been made about whether to approach Sputnik V developers following internal talks on the matter.

Still, the discussions among EU governments show a remarkable change of tack over the Russian vaccine.

For months, the EU expressed doubts about Sputnik V citing a lack of data and dubbing the vaccine a foreign policy propaganda tool of the Kremlin.

On Feb. 17, European Commission head Ursula von der Leyen questioned Russia’s reasons for exporting millions of doses despite a slow roll-out at home, where fewer people have been vaccinated proportionally than in the EU, based on public data.

Even last week, Charles Michel, who chairs summits of EU leaders, again cast doubt on Russia’s motives for promoting Sputnik V.

“We should not let ourselves be misled by China and Russia, both regimes with less desirable values than ours, as they organise highly limited but widely publicised operations to supply vaccines to others,” he said. “Europe will not use vaccines for propaganda purposes.”

There were no official reactions from Moscow and Beijing to Michel’s comments, though Russia has previously accused the EU of politicising the issue of COVID-19 vaccines.

DRAGHI FACTOR

However, the narrative about Sputnik within the EU had already started to shift after peer-reviewed trial data published on Feb. 2 showed it was 92% effective, higher than the Oxford University/AstraZeneca shot and close to the Pfizer/BioNTech and Moderna vaccines.

There was a new twist on Feb. 25, when Mario Draghi made his debut at an EU summit as Italy’s new prime minister.

The former European Central Bank chief, who is highly regarded in Brussels for saving the euro from its worst crisis years earlier, took an assertive stand on vaccines to quicken the pace of both inoculations and production in Europe.

He told fellow leaders the EU must buy more doses, including from outside the bloc, and expand vaccine production.

Italy, traditionally supportive of a softer stance on Moscow, is now pushing EU governments to consider Sputnik V. At a meeting of EU diplomats last Wednesday, Italy’s representative urged the EU to broaden its supply of vaccines, including with the Russian shot, an official who attended the meeting said.

A spokesman for the Italian representation to the EU declined to comment.

Asked about Sputnik V, Italy’s health minister said earlier in March: “If a vaccine works and the regulators tell us that it is safe, nationality is of little interest to me. Italy is ready to collaborate with the Russian government”.

Italy’s overtures follow Draghi’s appointment at the helm of a government supported by the right-wing League party and Silvio Berlusconi’s centre-right Forza Italia, both of which have long called for EU sanctions on Moscow to be phased out.

EU officials have said, however, that doses are desperately needed now and Sputnik V could come too late to be useful for the bloc when deliveries of the 1.3 billion shots it has already ordered are expected to accelerate later this year.

‘IT’S RUSSIAN IT’S BAD’

Still, any EU reluctance to launch talks with Sputnik V developers could weaken if the European Medicines Agency (EMA) approves the vaccine and if member states agree to make the shot at plants in their territories.

On March 4, the EMA launched a rolling review of Sputnik V, the first step in a process that could lead to its EU-wide approval. An EU official familiar with the process said a decision on possible authorisation could come as early as May.

On the production front, Russia’s RDIF sovereign wealth fund last week signed an agreement with Swiss-based pharmaceutical company Adienne to produce small amounts of Sputnik V in Italy, though Rome was not involved in the arrangement.

But if Rome agrees a deal with ReiThera, it would be the most significant endorsement of Sputnik V yet, eclipsing agreements Moscow has sealed with other countries, including Brazil, Argentina and India.

Berlin has also expressed interest in producing Sputnik V in Germany, while RDIF has said it was discussing production deals with several EU countries.

RDIF declined to comment on specific deals with companies to manufacture Sputnik V within the EU, or on any possible change of stance by the bloc towards the vaccine.

Back in Brussels, one EU diplomat said that if the EMA approves Sputnik V, the bloc would likely split between those members in favour of cooperating with Russia and those against.

Ties between Russia and the West, already at post-Cold War lows, have come under renewed pressure recently over the treatment of Kremlin critic Alexei Navalny, whose jailing prompted Brussels and Washington to impose sanctions on Moscow.

“We will fall into the usual divide: ‘it’s Russian it’s bad’ versus ‘well, come on, we need to work together with those people’,” the diplomat said.

“There are some who will not want to give (Russia) this propaganda victory, and there are others who will be seeing this as an opportunity to actually show that we are cooperating.”

https://www.reuters.com/article/us-health-coronavirus-eu-vaccines-insigh/unthinkable-eu-considers-getting-a-vaccine-boost-from-russias-sputnik-idUSKBN2B70KO

Why Eli Lilly's Successful Alzheimer's Disease Study Was So Disappointing

 Attention for Eli Lilly (NYSE:LLY) has been blowing up since the company announced success for its experimental new Alzheimer's disease drug. Unfortunately, the results strongly suggest that Eli Lilly and Biogen (NASDAQ:BIIB) have a lot more work to do.

How can a clinical trial that succeeded also foreshadow a slow-motion trainwreck? Strap in for some nuance.

Technically a success

The phase 2 Trailblazer trial rounded up hundreds of people with early stage Alzheimer's disease and treated them with either a placebo or donanemab to see if the experimental antibody could prevent their disease from getting worse. 

Earlier this year, Eli Lilly sparked a lot of hope for donanemab by telling everybody the Trailblazer trial met its main goal. That goal was a significantly improved score on a relatively new test to measure patients' cognitive and functional abilities. After treating 257 patients for 76 weeks, test scores for those given a placebo deteriorated 46% further than test scores for patients randomized to receive donanemab. 

Donanemab works in the brain to reduce the formation of dangerous plaques made of amyloid protein fragments. After 76 weeks, comparing brain scans also showed huge amyloid plaque reductions for those given donanemab compared to those given a placebo.

Why donanemab disappointed

Donanemab significantly slowed patients' rate of decline on the integrated Alzheimer's disease rating scale. The iADRS combines a commonly used cognition test with a test that measures AD patients' ability to function as adults.

The FDA has never reviewed an application for a potential new Alzheimer's disease drug based on a successful iADRS score. That could be a big problem for Eli Lilly because the Trailblazer study assaulted trial participants with a battery of different tests and the iADRS was the only measurement in which donanemab provided a statistically significant benefit.

Moreover, the benefit wasn't any better than Eli Lilly reported for solanezumab years ago. This twice-failed amyloid remover from Eli Lilly couldn't meet its primary endpoint in phase 3 trials, but it did lead to significantly improved iADRS scores.

This isn't working

Donanemab is similar to solanezumab, except it appears far more effective at removing amyloid deposits and preventing their formation. This is why Eli Lilly was eager to make the iADRS test a primary endpoint for donanemab trials, and extra careful to select trial volunteers that already had lots of amyloid deposits to remove.

If the donanemab program went according to plan, more amyloid to remove, plus a better drug to remove it should have led to an iADRS score benefit that rang clear as a bell. What happened was far less satisfying.

Patients began the Trailblazer trial with average iADRS scores of 106 points out of a potential 141 points. After 76 weeks, those given a placebo averaged just 3.2 points lower than those given donanemab.

Unfortunately, those given donanemab didn't improve or even hold steady. In fact, their average scores fell by 6.9 points.

What's next

The Trailblazer trial is another clear sign that removing amyloid deposits isn't a surefire way to stop the progression of AD, but it appears to work well for some. Decades from now we'll probably think of AD as a collection of different diseases, just one or two of which respond to drugs like donanemab on their own. In the meantime, U.S. regulators have a controversial decision to make that could help us understand the connection between amyloid knockdowns and the disease.

The FDA is eager to approve an amyloid-clearing AD drug from Biogen called aducanumab even though independent experts unanimously agree that pivotal trial results didn't show evidence of a benefit. If approved, widespread adoption of Biogen's drug could elucidate just which AD patients respond well to amyloid knockdowns and which don't. The line between Biogen's and Eli Lilly's attempts to treat AD isn't a straight one, but donanemab's future depends on the FDA's willingness to bend the rules for aducanumab. 

Alzheimer's disease affects one out of nine adults over the age of 65 and a dearth of available treatments means the first one will become one of the top-selling drugs of its time. With such an enormous pot of gold at the end of this rainbow, we can't fault Eli Lilly for making further attempts with donanemab. Unfortunately, its chances of success don't look very good.

https://www.fool.com/investing/2021/03/15/eli-lilly-reports-underwhelming-alzheimers-disease/

Rubius Initial Clinical Data from Phase 1/2 Trial of Cell Therapy in Advanced Solid Tumors

 Rubius Therapeutics, Inc. (Nasdaq:RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics™, today announced initial clinical, pharmacodynamic and tumor trafficking data from its ongoing Phase 1/2 clinical trial of RTX-240 in patients with advanced solid tumors. The Company also shared tumor trafficking data from one patient with relapsed/refractory acute myeloid leukemia (AML) in the second Phase 1 arm of the study. The Company believes these data provide initial proof-of-concept of the RED PLATFORM® by providing evidence that red blood cells can be engineered to mimic the human immune system and stimulate adaptive and innate immunity to generate clinical responses in cancer patients with refractory disease.

The Company will host a conference call and webcast at 8:00 a.m. EDT to discuss this update. The audio webcast will be available on the Events and Presentations page within the Investors and Media section of the Rubius Therapeutics website. The update may also be accessed by dialing 1-800-289-0045 (domestic) or 1-615-622-8086 (international) five minutes prior to the start of the call and providing the passcode 1294064. An archived webcast will be accessible for 90 days after the event.

https://finance.yahoo.com/news/rubius-therapeutics-reports-initial-clinical-113900475.html