Oncology trial starts hit record levels as COVID disruptions ease

 Oncology trial starts reached record levels in 2021—particularly in rare indications—as disruptions in cancer care brought on by the COVID-19 pandemic began to ease, according to the IQVIA Institute for Human Data Science.

The return to pace after a disruptive two years, when patients stayed home and missed crucial checkups, is certainly good news. But the IQVIA Institute’s new report did show that oncologists reported more new patients presenting with cancer that had spread due to delays in diagnosis and screenings.

“Global oncology is a bifurcated tale of two very different worlds,” said Murray Aitken, executive director of the IQVIA Institute. “On the one hand, we are witnessing a remarkable surge in R&D and innovation, potentially leading to new therapies for unresolved cancers. On the other hand, the global oncology community and patients continue to struggle with the impact from delays in screenings, diagnoses and cancer care. Even with the bright outlook for R&D and innovation, it will take a while for the oncology community to work its way through these challenges.”

The new report, "Global Oncology Trends 2022," found that cancer trial starts were up 56% in 2021 compared to 2016, with a focus on rare indications. Meanwhile, a record 30 novel active substances for cancer launched around the world, bringing to 159 the total number of therapies that have hit the market since 2012.

Oncologists reported a continued decline in caseloads for the year, about 20% to 29% below what they saw pre-COVID. But cancer screenings in the U.S. have returned to normal levels. More than 30 million screenings for four common tumors were disrupted during the pandemic, which means delayed or missed diagnoses for an estimated 58,000 patients.

But spending on oncology R&D has nevertheless continued to accelerate and is expected to exceed $300 billion by 2026, the IQVIA Institute said. Spending rose to $185 billion globally in 2021. Major markets including the U.S., Europe and China are seeing growth spurred by innovation, with new products and brand volume offsetting new competition brought by the loss of exclusivity on older meds and biosimilars.

R&D is happening faster and faster, with many therapies going from patent filing to product launch in less than five years.

While the focus in oncology tends to be on metastatic or advanced cancers, the report noted that more research is focusing on early cancer and vaccines, with this field doubling in the past 10 years. The composite success rate for oncology trials has been overall trending downward since 2015, hitting 5.2% in 2021, while rare tumors saw a higher success rate at an average of 15.6%

Another trend is that emerging biopharma companies are becoming more prominent in cancer research. The IQVIA Institute found that 68% of the oncology pipeline came from these companies compared to 45% a decade ago.

The report also noted some concerning trends in the rollout of new therapies across countries. Differences in biomarker testing, adoption of novel therapies and infrastructure capacity means that some new treatments haven’t reached patients. For instance, checkpoint inhibitors are being used at rates two to three times higher in developed nations compared to lower income nations. Cell and gene therapies similarly are not being offered to all patients, although the number of centers with CAR-T offerings is growing.

The IQVIA Institute for Human Data Science provides research and analysis collected from life sciences analytics company IQVIA’s non-identified patient-level data.

https://www.fiercebiotech.com/biotech/oncology-trial-starts-hit-record-levels-covid-disruptions-ease-report

Bristol drug repairs neuronal damage in Alzheimer's mouse models

 In Alzheimer’s disease, the loss of neuronal nexus called synapse contributes to the progressive cognitive decline. Now, scientists at Yale University found that an experimental drug originally developed by Bristol Myers Squibb for schizophrenia repair that damage in mice.

The drug, coded BMS-984923, targets the metabotropic glutamate receptor 5 (mGluR5) protein. In a study published in Science Translational Medicine, the Yale team found that the drug restored synaptic connections in mouse models of Alzheimer’s. It also reduced toxic build-up of the tau protein in the animals’ brains, another hallmark of the neurodegenerative disorder.

Connecticut biotech Allyx Therapeutics has in-licensed the drug from Bristol Myers for further development in Alzheimer’s and has re-coded it as ALX-001. Stephen Strittmatter, M.D., Ph.D., a co-corresponding author of the study, is the scientific founder of the startup.

In a 2017 Cell Reports study (PDF), Strittmatter and colleagues showed that BMS-984923 can block amyloid beta oligomer signaling through mGluR5 without interfering with a neurotransmitter. The drug also rescued age-dependent memory loss in an Alzheimer’s mouse model.

A lot of the attention on Alzheimer’s treatment these days is focused on antibody drugs that could clear misfolded amyloid beta protein clumps in the brain. But growing evidence also suggests that soluble amyloid beta peptides known as oligomers, rather than the plaques themselves, are harmful to neurons.  The oligomers could impair synapses, which connect neurons and are responsible for passing along messages to enable cognition. And mGluR5 has been found to play an important role in spreading oligomers’ damaging signal.

This time around, the researchers used PET imaging to show that the compound effectively occupied mGluR5 sites in the brain of rodents and monkeys.

In two mouse models of Alzheimer’s, the drug restored synapse density in the animals’ brains. It prevented synapses from being tagged by the complement protein C1Q and therefore stopped the neuronal junctions from being engulfed by cellular scavengers.

The treatment also reduced toxic tau protein tangles, the team found. Accumulations of tau and beta amyloid have been shown to cause synapse loss.

Other research groups have also been examining ways to tackle Alzheimer’s by protecting synapses. A team at University of California, San Diego found that blocking the Vangl2 protein from neurons could stop amyloid beta from degrading synapses.

Yale, in collaboration with the National Institute on Aging, have already launched a phase 1 trial of BMS-984923 in healthy people. The clinical trial also aims to determine the drug’s mGluR5 site occupancy at different dosing levels. Because Alzheimer’s is a complex disease, BMS-984923 may have synergy with other therapies, the Yale team said.

https://www.fiercebiotech.com/research/bristol-myers-drug-candidate-repairs-neuronal-damage-alzheimers-mouse-models

Bristol Myers triples-down on Immatics, bringing deal to $4.2B

 It’s the rare triple down: Bristol Myers Squibb is once again revising a massive research collaboration with immunotherapy drug discovery biotech Immatics. BMS is adding new deal with $60 million upfront and $700 million down the line for at least two new programs, plus expanding its prior arrangement.

That brings the total value of the collaborations to $4.2 billion in biobucks. The deal was originally signed in 2019 by Celgene before it was absorbed into BMS, and BMS again inked an agreement with Immatics in 2021.

At this point, BMS has put a lot of cash on the line for Immatics, which has a market cap of just under $500 million—which begs the question: why not just buy the whole thing? Well, we asked.

"The expanded collaboration is another example of sourcing external innovation to advance our scientific leadership in core therapeutic areas," BMS said in a statement. "We feel the existing collaboration agreement provides significant potential opportunities for all parties involved."

Immatics went public in 2020 via a special purpose acquisition deal with Arya Sciences Acquisition, which helped fuel the biotech with $148 million in cash.

Back to the revised deal. So what does BMS see in this tiny biotech? The new agreement will involve Immatics’ gamma delta T cell-derived, allogeneic adoptive cell therapy platform, called ACTallo. The companies will develop multiple allogeneic, or so-called off-the-shelf, TCR-T and CAR-T programs.

Besides the initial two programs, BMS also has an option for up to four additional programs each. BMS will pay the upfront fee plus milestones and royalties.

Immatics will work on preclinical development of the first two programs, to be owned by BMS, receiving payments along the way as they progress. BMS will take over at the point of clinical development and handle commercialization.

But that’s not all. The companies are also expanding the 2019 collaboration, which focused on autologous T-cell receptor-based therapies, to add an additional target discovered by Immatics. The biotech will receive a $20 million upfront fee for this extra work plus milestones and royalties.  

BMS’ Rupert Vessey, who serves as executive vice president for Research & Early Development, touted the deal as a “an important part of our continued investment in next-generation cell therapies.”

In December 2021, BMS bumped up the Immatics partnership with a new $150 upfront payment, bringing the total value of the deal at that time to $770 million in biobucks. It was the pair's second collaboration and would focus on a TCR bispecific called IMA401.

In addition to the revised deal, Immatics also reported first-quarter earnings. The biotech has cash and cash equivalents totaling €252.7 million ($280 million) as of March 31, which grew from the €145.1 million ($161.1 million) recorded at the end of 2021. This bump comes from an upfront payment received from BMS but does not include the $80 million that was offered in the revised partnership announced today, according to the financial report. Immatics now projects its cash runway to last through the second half of 2024.

Revenue also went up, thanks to the licensing portion of the BMS collaboration for IMA401, which is part of the original deal that Immatics moved into clinical trials this year. Immatics will conduct a phase 2 study in 50 patients with solid tumors in Germany.

Immatics also has large partnerships with Amgen, GlaxoSmithKline and Genmab. 

https://www.fiercebiotech.com/biotech/bristol-myers-triples-down-immatics-bringing-deal-42b-total-biobucks-why-not-just-buy-it

Moderna, EU officials delay COVID-19 vaccine deliveries as demand falls

 Moderna won’t be delivering COVID-19 vaccine boosters to the European Commission (EC) on the timeline as originally expected as officials adapt to changing vaccination needs in the region.

The company reached a deal with European officials to amend their original supply agreement, pushing the delivery of boosters scheduled for the second quarter to later in 2022 or early 2023. The agreement also covers future boosters and vaccines that target specific variants.

The prior version of the supply deal came last February, when Moderna agreed to sell 150 million doses to Europe. The deal featured an option deliver another 150 million during 2022.

The new agreement aligns with current demand levels in the commission’s member states, Stella Kyriakides, Commissioner for Health and Food Safety, said in a statement.

More than 2 years into the pandemic, vaccine makers have produced billions of vaccine doses in Europe and exported many to low- and middle-income countries. In Europe, many countries have seen a drop in demand lately.

The amendment comes after EU health officials had a meeting last month to discuss a renegotiation of vaccine contracts amid declining demand. Separately, the health ministry of Bulgaria, the country with the EU’s lowest vaccination rate, asked for an “open dialog” with the commission and pharmaceutical companies.

In May, the commission reached a deal with Pfizer and BioNTech to delay delivery schedules.

Moderna produced more than 800 million doses last year. The company is projecting $21 billion in revenues from the vaccine this year.

https://www.fiercepharma.com/pharma/moderna-amends-european-commission-vaccine-delivery-agreement-europe-demand-wanes

VistaGen to Present Phase 2A Research for Adjustment Disorder with Anxiety

 VistaGen Therapeutics, Inc. (Nasdaq: VTGN) (VistaGen), a late clinical-stage, central nervous system (CNS)-focused biopharmaceutical company aiming to transform the treatment landscape for individuals living with anxiety, depression and other CNS disorders, today announced that the clinical trial abstract for its exploratory Phase 2A clinical study in adjustment disorder with anxiety (AjDA) for PH94B, its investigational rapid-onset pherine nasal spray with potential to treat multiple anxiety disorders, was accepted by the American Society for Clinical Psychopharmacology (ASCP) for the 2022 ASCP Annual Meeting taking place May 31 through June 3, 2022.

The clinical trial abstract for the Company’s ongoing exploratory Phase 2A clinical trial, entitled “Efficacy, safety, and tolerability of PH94B in adjustment disorder with anxiety: design of an exploratory phase 2A clinical trial,” describes the clinical trial protocol intended to evaluate PH94B’s potential to treat adults living with AjDA, a disorder with potential for increased prevalence during these uncertain times. PH94B is a first-in-class, odorless, tasteless rapid-onset (approximately 15 minutes) investigational pherine nasal spray with a novel mechanism of action (MOA) that regulates the olfactory-amygdala neural circuits of fear and anxiety and attenuates the tone of the sympathetic autonomic nervous system. VistaGen is also currently evaluating PH94B in the Company’s two PALISADE Phase 3 clinical trials for the acute treatment of anxiety in adults with social anxiety disorder (SAD).

https://www.biospace.com/article/releases/vistagen-to-present-ph94b-exploratory-phase-2a-research-program-for-adjustment-disorder-with-anxiety-at-american-society-for-clinical-psychopharmacology-annual-meeting/

Centessa to Discontinue Development of Lead Asset

 Shares of Centessa Pharmaceuticals fell Thursday after the company announced that it is discontinuing the development of its lead asset, lixivaptan, for autosomal dominant polycystic kidney disease (ADPKD). The decision will end a Phase III and open-label study, the company said.

Boston-based Centessa said the decision to terminate the development of lixivaptan in the ADPKD space was based on a “thorough reassessment of the commercial potential of lixivaptan” as a best-in-class therapy for patients with the disease. Additionally, the company noted “incremental development challenges and associated costs” following the recent observation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations in one subject in the open-label Alert study.

Centessa launched in 2021 following the merger of 10 private biotech companies and hit the ground running with a $250 million Series A financing round. One of the companies that combined to form Centessa, Palladio Biosciences, brought lixivaptan into the fold.

Lixivaptan is an oral, non-peptide new chemical agent that works by selectively suppressing the activity of the hormone vasopressin at the V2 receptor. ADPKD is a genetic, progressive disorder characterized by the growth of numerous cysts in the kidneys. The most common symptoms are kidney cysts, pain in the back and the sides and headaches. Other symptoms include liver and pancreatic cysts, urinary tract infections, abnormal heart valves, high blood pressure, kidney stones and brain aneurysms.

Centessa had already begun dosing patients in its pivotal Phase III Action study prior to the discontinuation of lixivaptan. Earlier this year, the company received a key patent in the United States that covers the use of lixivaptan for the treatment of ADPKD. Currently, the only approved medication for ADPKD is Otsuka’s Jynarque (tolvaptan). Jynarque does come with a black box warning as it can cause potentially fatal liver damage. Additionally, liver failure requiring transplantation has been reported in post-marketing studies.

Saurabh Saha, chief executive officer of Centessa, noted that the open-label Alert study was designed to provide an early assessment of lixivaptan’s safety profile in ADPKD patients who were previously treated with Jynarque but developed liver chemistry abnormalities.

“In assessing the recent data from a subject in the Alert Study, we believe that lixivaptan is unlikely to achieve the differentiated safety and tolerability profile Centessa required for further development of the program. Given the revised commercial potential of lixivaptan and our commitment to being financially disciplined, we made the data-driven decision to voluntarily discontinue development of lixivaptan,” Saha said in a statement.

He added that the company hoped lixivaptan would provide patients with ADPKD with a safer alternative to the current treatment regimen.

The discontinuation of the development of lixivaptan for ADPKD is expected to significantly extend the cash runway into 2026, the company noted.

Going forward, Saha said Centessa will continue to advance its innovative rare disease and immuno-oncology programs, and that the hope is to move those programs into the clinic over the next 12 to 24 months.

“With our decision to discontinue development of lixivaptan, we believe we are well-positioned with the capital and resources to execute these programs. We expect a significant reduction in annual cash burn and that our cash runway will now extend into 2026,” he said.

https://www.biospace.com/article/centessa-discontinues-development-of-lead-adpkd-asset-lixivaptan/

Baby Formula Out-of-Stock Hits Record 74%

Despite all the bluster from The White House on its actions to relieve the crisis, the baby formula shortage continued to worsen last week.

Earlier this week, President Biden crowed on Twitter at the actions he has taken to 'fix' the problem:

But, as Bloomberg reports, out-of-stock rates climbed to 74% nationally for the week ending May 28, according to data on 130,000 stores followed by Datasembly. The increase comes after rates spiked to 70% for the week ending May 21 from 45% the week prior.

Even more stunningly, ten states now have shortage rates at 90% or greater, with Georgia hardest hit at 94%.

So since the president was made aware of shortages, the crisis has only worsened, but then again, haven't we seen the same thing again and again (Afghanistan, gas prices...)

As Philip Wegmann detailed earlier via RealClear Politics, the Biden presidency was born from crisis. And that was by design.

The country was looking for stability during the chaos of COVID-19, and the former vice president offered a shaken electorate the promise of tested leadership and trusted experience. At the very least, Biden said he could offer an improvement over the reality television politics that had defined his opponent’s time in office. And that pitch worked. He won the White House, but more crises followed.

A land war in Europe, a persistent pandemic, an ugly end to the war in Afghanistan, and an unrelenting cycle of historic inflation: Each challenge came so quickly, compounding and cascading over the last, that White House staffers reportedly joked that a plague of locusts must be next. Instead, it was baby formula.

They didn’t expect a nationwide shortage, and neither did the president. “I don’t think anyone anticipated the impact of the shutdown of one facility – the Abbott facility,” Biden told reporters Wednesday, referring to the Abbott Laboratories Inc. plant in Michigan that went offline in February due to safety concerns and that has led to months-long scarcity.

But baby formula manufacturers did anticipate the impact three months ago, and moments before Biden started fielding questions from the press, they had just said as much in front of the cameras. Robert Cleveland, senior vice president for North American operations of the Reckitt Co., was the first of the manufacturers to speak, and he said he told Biden that “we knew from the very beginning this would be a very serious event.”

Tarun Malkani, president and CEO of Gerber, told Biden that his company might be a relatively small player in powdered formula but they were doing all they could out of a sense of “national duty.” He added that they were operating with the same level of urgency today that they did “when I got that first phone call informing me of the crisis situation.”

Murray Kessler, CEO of Perrigo Company, told Biden that as soon as his company heard about the recall “we could foresee that this was going to create a tremendous shortage.”

The other manufacturers present said the same, and yet the president admitted he wasn’t made aware of the gravity of the crisis until last month. Hadn’t those CEOs just told him they understood it would have a very big impact the moment the Abbott plant was shuttered, a reporter asked.

“They did,” Biden replied, “but I didn’t.”

That terse admission undercut the official administration line. The White House has insisted for weeks that they were quick to react and that they mounted a “whole-of-government approach” since the Food and Drug Administration issued the recall on February 17. Apparently, and at least according to Biden himself, this did not include the president until April.

Although late to comprehend the crisis, the months-long absence did not prevent Biden from telling families without baby food that he felt their pain. “There is nothing more stressful than the feeling like you can’t get what your child needs,” he said. “As a father and grandfather,” he added, “I understand how difficult this shortage has been.”

That empathy did not satisfy the press corps. Reporter after reporter pressed White House Press Secretary Karine Jean-Pierre with various iterations of the same question: What did the president know about the formula shortage and when did he know it? Jean-Pierre reiterated that the administration had taken a whole-of-government approach. “We’ve been working on this for months,” she insisted. “We’ve been taking this incredibly seriously.”

She said that the day after the Abbott plant went dark, the U.S. Department of Agriculture was cutting red tape to allow states more flexibility to purchase formula. And to get that plant back up and running safely, scientists at the FDA, she added, “have been working around the clock.”

It wasn’t until May though, three months after Abbott went dark and the industry began racing to meet demand, that Biden invoked the Defense Production Act. Store shelves were bare across the country by the time the president finally launched Operation Fly Formula to bring baby food into domestic markets from overseas.

But when did the White House get a call alerting the administration that perhaps the issue required presidential involvement? “I don’t have the timeline on that,” Jean-Pierre replied. “All I can tell you as a whole-of-government approach, we have been working on this since the recall in February.”

Another reporter asked a little later if the White House could detail the early steps that were taken: meetings or phone calls, for instance, or briefings back in February when the shortage first began. “I don't have that information,” the press secretary answered, promising to make that material public when it became available.

Was the White House spokeswoman calling into question the April date that Biden had just given, a third reporter asked. Had he misspoken? “No,” Jean-Pierre pushed back, “I am not questioning the president at all.” She hadn’t talked with the president on this topic, she said, before coming to brief the press.

Biden predicted earlier in the day that it would take “a couple more months” before supply returned to normal. Fully stocked shelves can’t come soon enough for families with newborns or for individuals with metabolic disorders who rely on special formulas that only Abbott manufactures. Nationwide, according to a Wall Street Journal analysis, 23% of powdered formula was out of stock last week. Another 11% was entirely out of stock, the paper reported, because of supply-chain shortages and inflation.

Other manufacturers besides Abbott, including those speaking at the White House Wednesday, have ramped up manufacturing to meet demand. Domestic production, Jean-Pierre told reporters, “has even increased from last year.” Eventually, the shortages will end. A larger question remains, though, one that gets to the central promise that Biden made during his campaign: How serious does an issue have to be before it is brought to the president's attention?

The press secretary ran through the timeline again as she had before, telling RealClearPolitics that “we did everything that we can to cut red tape, and now the Defense Production Act, flying in the formula from abroad. All of those things were actions we took to deal with this crisis.”

She did not answer the general question with any specificity other than to say, “There are always multiple crises happening that we are dealing with all at once.”

https://www.zerohedge.com/political/biden-admits-he-was-awol-until-april-baby-formula-crisis