EMA to quickly review Eli Lilly, Incyte arthritis drug for COVID-19 use

 The European Medicines Agency will conduct an accelerated review of Eli Lilly and Co's rheumatoid arthritis drug Olumiant for hospitalized COVID-19 patients getting oxygen, the agency said on Thursday, as the search for treatment options continues.

Olumiant, on which Lilly partners with U.S. drugmaker Incyte Corp, is the latest arthritis medicine to be repurposed in efforts to combat COVID-19, with other prominent examples Actemra from Roche Holding AG and Kevzara from Sanofi SA .

While Actemra and Kevzara are large-molecule monoclonal antibodies, Olumiant is a so-called Janus kinase (JAK) inhibitor small-molecule drug that works by blocking action of enzymes that play a role in immune system processes that lead to inflammation.

The EMA is quickly reviewing data from Eli Lilly of two randomized trials of hospitalized patients. Olumiant, also called baricitinib, was given emergency use authorization in the United States in November 2020 to be deployed in combination with Gilead Sciences Inc's remdesivir, for COVID-19 patients.

"EMA will communicate on the outcome of its evaluation, which is expected to reach an opinion by July unless supplementary information is needed," the agency said in a statement.

While Olumiant, whose anti-autoimmune action has also made it a candidate to treat certain types of hair loss, has shown promise against severe COVID-19, not all JAK inhibitors have succeeded. Novartis AG's Jakavi, also called ruxolitinib and used to treat some forms of blood cancer, showed no significant benefit for COVID patients.

Repurposing drugs for COVID-19 can be lucrative, as Roche has reaped hundreds of millions in additional sales for Actemra since the pandemic began after trials that have offered mixed results. Olumiant sales rose 39% in the first quarter to about $194 million.

https://finance.yahoo.com/news/ema-quickly-review-eli-lilly-154001307.html

Can unclogging brain's drainage system up efficacy of Biogen aducanumab in Alzheimer's?

 One popular theory in the quest to develop cures for Alzheimer’s disease is that targeting the toxic clumps of the protein beta-amyloid in the brain that are a hallmark of the disease could ameliorate symptoms. One such anti-amyloid drug, Biogen and Eisai’s aducanumab, has shown mixed efficacy in slowing cognitive decline in two clinical trials, while several similar candidates have simply failed to register any benefit, leaving many doubtful about the strategy.

Now, a research team led by scientists at Washington University School of Medicine in St. Louis has proposed a possible explanation for the disappointing clinical outcomes. In a new study published in Nature, backed by findings in mice, the researchers pointed to the brain’s newly discovered drainage system, called the meningeal lymphatic system. The researchers suggested that drugs could be developed to enhance its function to improve the efficacy of treatments like aducanumab in Alzheimer’s.

PureTech Health, which holds an exclusive license to the underlying intellectual property, is now developing novel therapeutics to modulate lymphatic flow in the central nervous system. The company hopes to target a range of neurodegenerative diseases.

“The lymphatics are a sink,” Jonathan Kipnis, Ph.D., a co-author of the study, explained in a statement. “Alzheimer’s and other neurodegenerative diseases such as Parkinson’s and frontotemporal dementia are characterized by protein aggregation in the brain. If you break up these aggregates but you have no way to get rid of the debris because your sink is clogged, you didn't accomplish much. You have to unclog the sink to really solve the problem.”

In 2015, a team led by Kipnis discovered the lymphatic system in the brains of mice. Then in 2018, he led a study that showed that ablating the meningeal lymphatic system increased beta-amyloid deposits in mice. So he hypothesized that the disappointing performance of anti-amyloid drugs may be explained by functional differences in the lymphatic drainage system in individual patients.

To test the theory, Kipnis and colleagues used versions of aducanumab and another amyloid-targeting drug BAN2401 in a mouse model of early Alzheimer’s that’s also characterized by beta-amyloid buildup. The idea was to test whether improving function of the lymphatic drainage could impact the effectiveness of the drugs.

Mice with ablated meningeal lymphatics showed significantly higher buildup of beta-amyloid plaque than did controls with intact drainage systems, the scientists found. Mice with impaired lymphatic drainage also showed decreased influx into the brain of the antibody drugs from the surrounding fluid, suggesting reduced targeting of the plaques, the team noted.

The researchers also observed changes in a type of immune cell in the brain called microglia, which work as scavengers that remove dying cells and other debris. Crippling lymphatic drainage shifted microglia to an inflammatory state, which could contribute to neurodegeneration, the researchers suggested.

What’s more, genes related to antigen processing and presentation and T-cell activity were turned down in the microglia of mice with damaged lymphatic systems, the team found. This could potentially impair the efficacy of passive immunotherapies such as amyloid-targeting antibodies, they said.

Overall, the gene-expression patterns in microglia from mice with damaged lymphatics resembled those from people with Alzheimer’s, the team showed.

To explore the therapeutic potential of meningeal lymphatics, the scientists combined aducanumab or BAN2401 with a virus-mediated vascular endothelial growth factor-C, in the hopes of expanding the network of meningeal lymphatic vessels. Mice that got the combos showed significantly decreased beta-amyloid accumulation as compared to those that were given the anti-amyloid drugs alone, according to the team.

The findings suggest it might be possible to develop drugs that target microglia and the brain blood vessels—both of which are important in Alzheimer’s—by modulating the function of the lymphatic vessels, the researchers wrote in the study. Future studies could examine the genetic signatures in humans to infer information about the integrity of the brain’s lymphatic system, so personalized combination treatments to slow the progression of Alzheimer’s can be developed, they suggested.

https://www.fiercebiotech.com/research/could-unclogging-brain-s-drainage-system-improve-efficacy-biogen-s-aducanumab-alzheimer-s

In a first, FDA issues Acceleron a serious rebuke for trial data delay

 The FDA is on the verge of slapping Acceleron Pharma with up to a $10,000 fine for failing to publish a summary of its trial data results on a cancer combo using its old med dalantercept.

The summary results information, which is the basic form of the data (without individual patient information), is required by federal law to be uploaded to the government trials site, ClinicalTrials.gov., within one year of a study being finished.

The FDA, which is in charge pf policing this, has had a light-handed approach, sending out more than 40 Pre-Notices of Noncompliance, which in essence are verbal warnings for those companies to get their acts together and comply, but not going beyond this.

But now, and perhaps in a sign of things to come, the FDA has for the first time decided to take actual potentially criminal action against a company that failed to do this: In the crosshairs is Acceleron Pharma and a trial for its now-defunct oncology asset dalantercept, which started a midstage trial all the way back in 2012 in kidney cancer and combined with Pfizer’s approved Inlyta.

In the end, Acceleron actually threw out the drug as it turned out to be a flop, but it is yet to release the summary results on ClinicalTrials.gov, which could cost it up to $10,000 in a fine. It has 30 days to comply.

“The FDA is authorized to seek civil money penalties for Acceleron’s violation, including additional civil money penalties if Acceleron fails to submit the required information within the 30-day period,” the FDA noted in a statement.

“The FDA takes its role in enforcing the ClinicalTrials.gov registration and results information submission requirements extremely seriously and we will continue to encourage voluntary compliance with these requirements,” it added, in what is a ominous response for the rest of the industry.

In the U.K. and Europe, concerns about delaying or even hiding data (usually negative trial results) from public scrutiny have been growing for the last decade or so, with pressure and lobby groups pushing governments and regulators to do more when it comes to keeping a consistent, transparent approach to publishing full trial results.

The U.S. has been a little slower to come around to the idea but the FDA now looks as if it may be turning a corner. Taking to Twitter, the acting (and perhaps future full-time) FDA Commissioner Janet Woodcock, M.D., said: “Transparency about the results of clinical trials is important for the integrity of the whole enterprise.”

Ben Goldacre, M.D., a co-founder of the AllTrials data transparency group and Bad Pharma author, said the threat of a fine was welcome but added that there was now “Only $19 billion more to go” when it comes to fines.

The tracker of studies that should have reported their results in the U.S., which came into full force only in 2018, believes the FDA could have raked in more than $19 billion in similar fines had it taken unilateral action. It tallies that only 72% of trials have so far been reported.

https://www.fiercebiotech.com/cro/a-first-fda-issues-a-serious-rebuke-for-trial-data-delay-as-it-looks-to-get-tough

LabCorp, on COVID-19 testing wave, exceeds own expectations with $4.2B Q1 revenue

 The “new normal” of 2021 represents a delicate balance, where businesses are resuming operations amid rising vaccination rates, while the COVID-19 pandemic remains very much in play. In this strange limbo, LabCorp, for one, is thriving.

The lab testing giant reported first-quarter earnings that so surpassed its own estimates—and those of external analysts—that it bumped up its predictions for the rest of the year.

The higher-than-expected results were driven not only by LabCorp’s molecular and antibody tests for COVID-19, but also by steady increases in biopharmaceutical companies’ drug development efforts and the returning demand for its non-COVID diagnostics, Chairman and CEO Adam Schechter said in a statement.

In total, LabCorp saw its revenues jump to $4.16 billion for the first three months of the year, a nearly 50% increase compared to 2020's initial quarter. The company’s net earnings, meanwhile, registered a billion-dollar annual increase that brought it firmly out of the red, from last year’s $317 million loss to approximately $770 million in earnings.

As a result, LabCorp upped its outlook for the remainder of 2021. The company is now expecting total annual revenues to increase by 2% to 6.5%, compared to its previous predictions that revenues would fall somewhere between a 1% loss and a 4.5% increase.

The vast majority of the quarter’s revenues were driven by organic growth, one-third of which came from COVID testing alone. Within just the company’s diagnostics segment, COVID testing made up more than half of the gains, which contributed to an increase of 62%.

That growth reflects LabCorp’s efforts throughout the quarter to expand the availability and scope of its coronavirus offerings. Earlier this year, LabCorp added DiaSorin’s high-sensitivity antigen test to its diagnostic menu and was tapped by the Centers for Disease Control and Prevention to launch a large genomic study to track new mutations of the coronavirus as they spread to the U.S.

And in February, the company partnered with Walgreens to begin offering its Pixel at-home PCR test over the counter at up to 6,000 the chain’s locations around the U.S.

But LabCorp hasn’t put all its eggs in the COVID-19 basket. Even as Schechter noted in a conference call with investors that “our fight against this virus is not over,” he added that LabCorp’s COVID testing volume has declined, in line with a national trend linked to increased vaccinations.

Indeed, while LabCorp improved its annual outlook across the entire business, its expectations for the COVID testing business remained stagnant, with an expected revenue loss of 35% to 50% across 2021.

To maintain the upward trajectory of the first-quarter results—and meet its own newly updated financial goals—LabCorp will therefore double down on its work outside of the realm of COVID to develop new testing solutions and assist biopharmaceutical partners in bringing new drugs to clinical trials, Schechter said.

That work has already begun: In the first quarter of the year, LabCorp forged partnerships with several insurance providers and the Department of Defense to make lab testing more available to patients and expanded its existing collaboration with PathAI to use AI algorithms to accelerate LabCorp-managed clinical trials.

https://www.fiercebiotech.com/medtech/labcorp-still-riding-covid-19-testing-wave-exceeds-its-own-expectations-4-2b-q1-revenue

BeiGene Brukinsa in 'near best case scenario' v. Imbruvica in key CLL trial: analyst

 BeiGene’s argument for its BTK inhibitor Brukinsa is that it’s a better drug than AbbVie and Johnson & Johnson’s first-to-market Imbruvica in terms of both efficacy and safety. Now, it appears to have data to back its case—at least in part.

In a head-to-head trial in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), Brukinsa shrank tumors in significantly more patients than Imbruvica did by investigator assessment, BeiGene said Wednesday.

But when it came to the more neutral evaluation by an independent data review committee, the tumor response improvement by Brukinsa didn’t meet the statistical significance bar at the interim analysis.

Despite the mixed findings, SVB Leerink analyst Andrew Berens wrote to investors that the results were “a near best case scenario” for Brukinsa at this point.

BeiGene plans to discuss the data with global regulatory authorities and share the findings at an upcoming medical conference. The trial remains ongoing to see whether Brukinsa can perform better in stalling cancer progression or preventing death. Early signs showed a trend favoring Brukinsa on the progression marker, BeiGene said.

The latest results come from the phase 3 Alpine study, BeiGene's second ambitious head-to-head trial comparing Brukinsa against Imbruvica. Back in late 2019, Brukinsa failed to outdo Imbruvica in patients with Waldenstrom macroglobulinemia in the phase 3 Aspen trial.

In that study, BeiGene's newcomer didn’t significantly beat the market leader at clearing all signs of cancer or provoking what’s called “very good” partial response. At that time, Berens noted that BeiGene might have aimed too high in hoping to demonstrate that Brukinsa could double Imbruvica’s response rate. Brukinsa turned in a 28.9% response rate in the study, higher than Imbruvica’s 19.8%.

Compared with Waldenstrom’s, CLL/SLL is a much larger indication. Less than 10% of Imbruvica’s sales came from Waldenstrom’s, SVB Leerink analyst Geoffrey Porges noted in an analysis in late 2019, citing EvaluatePharma data. At the time, he said the Alpine study, which BeiGene just reported, was “likely to be the most significant comparison” between Brukinsa and Imbruvica.

Imbruvica is currently the clear leader within the BTK drug class, with 2020 global sales of $8.43 billion between AbbVie and Johnson & Johnson. By comparison, Brukinsa only brought in $41.7 million last year, its first full year on the market since the FDA go-ahead in late 2019 for previously treated mantle cell lymphoma.

Efficacy is just one side of the story in the competition. In Aspen, industry watchers already noted a generally better safety and tolerability profile for Brukinsa over Imbruvica. With the current Alpine trial, BeiGene has formalized that comparison.

On a secondary endpoint, Brukinsa showed a statistically significant lower risk of irregular heartbeat, an important safety concern that can lead to heart-related problems such as stroke and heart failure. Brukinsa wasn’t the first BTK player to tout such a safety advantage; AstraZeneca in January said its Calquence also topped Imbruvica on that heart safety marker in a CLL trial.

Even though the Brukinsa’s efficacy advantage may look marginal, the safety differences are “clinically and commercially meaningful,” Porges said of the Aspen trial in his earlier note.

The tumor response data from Alpine could score Brukinsa an FDA go-ahead in relapsed or refractory CLL/SLL. And the phase 3 Sequoia study that’s pitting the drug against the combination of bendamustine and rituximab in newly diagnosed patients could also read out top-line data this year.

Even before those regulatory decisions play out, the National Comprehensive Cancer Network already started recommending Brukinsa for both first-line and second-line treatment of CLL/SLL in December. 

https://www.fiercepharma.com/pharma/beigene-s-brukinsa-after-one-miss-tops-imbruvica-all-important-cll-head-to-head-trial-or

J&J scores in talc appeals as NJ court knocks down $117M verdict

 Johnson & Johnson has been hit with billions in talc verdicts, but it's had mixed success in appeals. With a new decision Wednesday, the company chalked up its latest appeals win. 

A court in J&J's home state of New Jersey struck down a $117 million verdict against the drugmaker originally handed down there in 2018, Bloomberg reports. The court ruled that the trial judge shouldn’t have allowed certain expert testimony, so J&J and its talc partner Imerys—which has since declared bankruptcy—deserve another trial.  

J&J's appeals win comes in the case of retired banker Stephen Lanzo, who argued that decades of talc use caused him to develop mesothelioma. 

A J&J spokeswoman said the opinion marks a “rejection” of the plaintiffs’ courtroom strategy of using paid experts to “present junk science that purports to find asbestos where there is none." 

Even considering the appeals win, J&J faces significant legal challenges ahead—both over its talc marketing and over its sales of opioid painkillers.  

In a 2018 trial, a Missouri jury ordered Johnson & Johnson to pay $4.69 billion after hearing the combined claims of 22 women who alleged the company’s talc powder caused their ovarian cancer. Last summer, the Missouri Court of Appeals for the Eastern District reduced the verdict to $2.1 billion. 

J&J has appealed the verdict, but the Missouri Supreme Court refused to take up its case. J&J is now appealing at the U.S. Supreme Court, and several business groups backed the company’s petition in recent court filings.  

It’s far from certain that the Supreme Court will take up the case, though. In last year’s financial results, the company recorded a nearly $4 billion litigation charge that it said was “primarily associated with talc related reserves and certain settlements.”  

Meanwhile, on the opioid front, the company has set aside $5 billion as it works through potential settlements on thousands of cases from localities and states.  

J&J is among a group of defendants facing an opioid trial in California. A talc trial is also ongoing in that state, Bloomberg reports. 

https://www.fiercepharma.com/pharma/johnson-johnson-scores-appeals-as-court-knocks-down-117m-talc-verdict

How much COVID-19 vaccine money is on the table? $157B through 2025: report

 Drugmakers who seized the opportunity to develop vaccines against the coronavirus are on their way to reaping significant revenues.

Exactly how much money is on the table?

In its annual forecast for global drug spending, the IQVIA Institute for Human Data Science put the figure at $157 billion through 2025.

It’s one of the many intriguing projections in this edition of IQVIA's annual drug spending forecast, the group’s first since the coronavirus pandemic put the worldwide economy on tilt.

For example, IQVIA projects global spending on medicines to reach $1.6 trillion by 2025, an increase from $1.25 trillion in 2019, representing annual growth of 3% to 6%. The $1.6 trillion figure does not include spending on coronavirus vaccines.

“We reflect what we expect to be happening over the next five years in terms of the drivers of change in demand for medicines and spending on medicines,” IQVIA executive director Murray Aitken explained in an interview.

In regard to global COVID-19 vaccine spending, IQVIA projects roughly $53 billion this year and $51 billion in 2022. The group sees a precipitous drop in total spending in 2023, to roughly $23 billion. 

The spending decrease over time can be attributed mostly to a drop in price rather than demand, Aitken said. While IQVIA puts the average cost per dose at $22 this year and $19 in 2022, Aitken sees prices falling to approximately $9 per dose by 2023, then to $7 by 2024 and all the way to $5 by 2025.

“We think the prices will keep coming down as we get beyond this immediate period of trying to get everyone vaccinated,” Aitken said. “There are 11 vaccines in use in one part of the world or the other and there may be more coming, so we can expect that prices will decline over time.”

Other factors that will influence global vaccine spending include an increased availability of single-shot options, an increased supply to developing countries and the need for booster shots for those who have already been vaccinated.

In coming to its estimates, IQVIA also took into consideration planned global manufacturing capacity, vaccinations to date, announced rollout strategies and company contracts.

The group assumed an average of 1.8 vaccine doses per person this year and next. From 2023 to 2025, when boosters will presumably be in use and more single-shot vaccinations will be available, IQVIA shifts the average to 1.3 doses per person.

Another assumption in the model: IQVIA believes that by the end this year, 40% of the world’s population will be in countries that have achieved herd mentality. By the end of 2022, 70% of the world’s population will be vaccinated.

For the purpose of the estimate, IQVIA also assumed one-shot boosters on a two-year cycle in the 2023 to 2025 period, though this issue has yet to be resolved by vaccine producers.

Making projections during a pandemic is risky business, IQVIA admits in its report. 

“The impact of COVID-19 defied expectations throughout 2020 but the evolution from pandemic to endemic is reasonably certain even if the interplay between vaccination levels and periodic outbreaks around the world remains challenging to predict," the group said.

https://www.fiercepharma.com/pharma/how-much-covid-19-vaccine-money-table-157b-through-2025-analyst