3 proteins IDd with potential to prevent heart failure after heart attack

 Scientists working to develop new therapies and treatments for heart failure patients have discovered three proteins that can be injected immediately after a heart attack, which have the potential to preserve heart function following an attack.

Positive preclinical data in Science Translational Medicine, published today, outlines the mechanisms of the three proteins, which have been shown to restore heart function following a heart attack in mice.

Heart failure is the primary cause of death and disability globally, affecting approximately 64 million people worldwide according to the British Heart Foundation. There is currently no effective therapeutic treatment.

Led by Mauro Giacca, Professor of Cardiovascular Sciences at King's College London, researchers developed an innovative technology called FunSel that searched for proteins that could protect heart cells against the rapid cell death that typically occurs following a heart attack.

Forcefield Therapeutics, a pioneer of best-in-class therapeutics to retain heart function via protection of cardiomyocytes, which was launched in 2022 backed by leading healthcare investor Syncona, is undertaking the development work to enable clinical trials in patients in the future. The work originated at the International Center for Genetic Engineering and Biology (ICGEB) and the University of Trieste, Italy.

Heart tissues from mice after heart attack, treated with either a control or the Chrdl1 protein. Credit: G. Ruozi, et al., Science Translational Medicine (2022)

Funsel, a protein "search engine" screens a library of human proteins to identify those with therapeutic potential, in an unbiased manner (unconstrained by the bias that researchers typically bring to drug development). Starting from a library of over 1,000 proteins, it identified three, (Chrdl1, Fam3c and Fam3b) which have been shown to prevent cardiac damage in mice after a heart attack and preserve cardiac function over time.

According to the British Heart Foundation, one person every five minutes is admitted to hospital with a heart attack in the UK. While 7 out of 10 people survive, heart attack is the main cause over time of heart failure—a condition that now affects almost one million people in the UK and 64 million worldwide.

Heart sections 60 days after heart attack in mice treated with various viral vectors, including a control and Chrdl1. Credit: G. Ruozi, et al., Science Translational Medicine (2022)

Heart failure after a heart attack is caused by the irreversible loss of cardiac cells, hence the need to develop effective therapies to prevent the death of these cells.

"This is the very first time that potentially curative factors for the heart are directly identified for their therapeutic potential," said Professor Mauro Giacca, Professor of Cardiovascular Sciences at King's College London. "Any of the three proteins we have identified can be administered immediately after a heart attack to minimize cardiac damage and thus prevent heart failure. There has been no significant development in this field for a long time, so we are very excited by this discovery."

Richard Francis, Chief Executive Officer of Forcefield Therapeutics, said, "Heart failure continues to have a devastating impact on public health and, despite the remarkable efforts in disease management, the long-term prognosis remains poor.

"Heart attack is the main acute cause of heart failure, providing a significant economic burden upon healthcare systems globally and reducing the healthy life span of those affected. This research is exciting not only because of the potential it offers for heart medicine, but also because it's a great example of academia and business, with the support of the UK's leading heart charity, collaborating effectively to bring a potential therapeutic to patients at speed."

Professor Ajay Shah, Director of the British Heart Foundation Center for Research Excellence at King's College London, said, "This is early-stage data but if the results we have seen in mice are borne out in human trials, the potential for this therapeutic is extremely significant and could revolutionize treatments for patients at risk of heart failure. There are no effective protective therapeutics to prevent the typically rapid deterioration of heart tissue in the aftermath of a MI so this is a major breakthrough in this field."

Professor James Leiper, Associate Medical Director at the British Heart Foundation, said, "Halting damage to the heart after it has become injured is a huge challenge in cardiology, but this major development has the potential to spearhead a new type of treatment to help protect and minimize damage after a heart attack. We're proud to support such a ground-breaking discovery that will hopefully lead to new protective medicines in the future."

After successful preclinical testing, first clinical trials in humans will take place in the next two years.

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New treatment shows promise in preventing heart failure after heart attack

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More information: Giulia Ruozi et al, Cardioprotective factors against myocardial infarction selected in vivo from an AAV secretome library, Science Translational Medicine (2022). DOI: 10.1126/scitranslmed.abo0699

https://medicalxpress.com/news/2022-08-proteins-potential-heart-failure.html

CMS aims to streamline Medicaid, CHIP enrollment

 The Biden administration proposed new regulations aimed at overhauling the application and renewal processes for Medicaid and other government programs, including that ensuring that a beneficiary's returned mail doesn’t automatically lead to coverage denials. 

The Centers for Medicare and Medicaid Services released a proposed rule that makes changes to the enrollment process for Medicaid, Children’s Health Insurance Program (CHIP) and Basic Health Programs. The changes include new requirements for states, which are busy preparing for the unwinding of the COVID-19 public health emergency, and with it a continuous coverage requirement in Medicaid. 

“This proposed rule will ensure that these individuals and families, often from underserved communities, can access the health care and coverage to which they are entitled – a foundational principle of health equity,” said CMS Administrator Chiquita Brooks-LaSure in a statement. “In addition, this proposed rule will help more people pay their Medicare premiums by making it easier for them to enroll in the Medicare Savings Programs.”

The agency is proposing to limit renewals once every 12 months as well as allow applicants 30 days to respond to any requests for information. States also must create a clear and consistent process for how beneficiaries can renew their coverage.

In addition, there are specific guidelines which a state must abide by before they drop off a beneficiary due to returned mail. 

“Many of the individuals we serve in Medicaid and CHIP move frequently and lose coverage because they do not get the coverage [notice] in the mail,” said Daniel Tsai, the director of Medicaid and CHIP, on a call with reporters Wednesday.

Other proposed changes include:

• Ensure automatic enrollment with limited exceptions into Qualified Medicare Beneficiary group;
• Establishing a clear process to prevent the termination of an eligible beneficiary that should transition from Medicaid and CHIP if their income changes or if a beneficiary is eligible for another program;
• Allowing CHIP beneficiaries to re-enroll or still be enrolled without any lockout period if they fail to pay premiums and remove waiting periods and lifetime or annual benefits in CHIP;
• Creating standardized timeframes for when renewals must be completed. The regulation clearly “defines the types of eligible determination information and documentation to be maintained by states,” according to a fact sheet on the rule. States also have specific timelines to complete Medicaid and CHIP renewals; and
• New guidelines to ensure that if a beneficiary returns their information late are still properly evaluated for “other eligibility groups prior to being terminated,” the agency said.

The proposed rule could bring new requirements for states right as they must prepare for the end of the COVID-19 PHE. At the start of the pandemic, Congress increased the federal matching rate for Medicaid payments but only if a state agreed to not drop anyone off Medicaid for the duration of the PHE. 

Health and Human Services (HHS) is expected to renew the PHE again this October for another 90 days. 

States in the meantime have been creating new processes and outreach efforts to alert Medicaid beneficiaries that they could lose coverage and have to redetermine their eligibility.

Senior CMS officials told reporters Wednesday that it will take some time for the rule to finalize things, but the PHE unwinding could help with implementation.

“We think a lot of the tactics will align well with this rule,” one official said.

https://www.fiercehealthcare.com/payers/cms-aims-streamline-medicaid-chip-enrollment-process

Oscar Health loses major tech customer

 Health First Health Plans, an early adopter of Oscar Health's tech stack, is pulling the plug on the project amid implementation challenges.

The Florida-based health insurer intends to terminate its deal with Oscar's information tech platform +Oscar and "transition the services from +Oscar to Health First, effective as early as January 1, 2023," the insurtech revealed in a Securities and Exchange Commission filing Tuesday. 

It marked Oscar's first full-service tech agreement but there were major implementation snags due to the complexity and size of the project.

Under a deal signed last year, Oscar was contracted to provide administrative functions and services for the insurer, along with giving it and its individual commercial and Medicare Advantage members access to Oscar’s technology platform. 

Oscar will lose out on up to $60 million in administrative services revenue this year. The company said it does not expect the loss of the contract to impact its earnings or net loss in 2022.

"The company is actively moving forward with the development and sale of +Oscar’s Campaign Builder, which is consistent with the company’s focus on new modular and Software as a Service offerings," the company said in the SEC filing.

Oscar "continues to be committed to growing the +Oscar business and continuing to serve current clients," the company said.

Earlier this month, Oscar Health said it was pressing pause on new deals for its technology platform for more than a year as it manages issues in integrating with Health First Health Plans.

Oscar CEO Mario Schlosser told investors during the company's second-quarter earnings call it planned to hold off on additional full-service deals for its +Oscar platform for the next 18 months. Oscar formally launched its tech platform business in April 2021.

The +Oscar tech stack aims to simplify administrative tasks and boost the member experience. 

The partnership with Health First was set to go live at the start of this year but faced significant challenges due to the complexity of integration, Schlosser said. Putting a pin in new deals allows Oscar to address issues with implementation without overextending its capabilities.

Chief Financial Officer Scott Blackley said on the August 11 call that Oscar is still negotiating potential deals in the space even as it focuses on addressing the implementation challenges, as there is a demand for such services.

The company is still pushing toward profitability and is focused on turning a profit in its insurance business by next year and overall by 2025. Oscar posted $1 billion in revenue for the second quarter and a net loss of $112.2 million, up from a $73.3 million loss in the prior-year quarter.

https://www.fiercehealthcare.com/payers/oscar-health-loses-major-tech-customer-amid-integration-challenges

AWS selects 10 startups for its 2022 Healthcare Accelerator

 Amazon Web Services tapped 10 startups as finalists to participate in its 2022 healthcare accelerator focused on health equity, it announced Wednesday.

The cohort of 10 startups, selected from more than 250 applicants, pitched solutions aimed at improving access to care and addressing social determinants of health, the company said. Those social drivers range from expanding access to medical transport to helping unhoused patients reach housing and health goals. 

The program will run for four weeks and will offer technical and business mentoring, up to $25,000 in AWS computing credits and opportunities to collaborate with existing AWS clients, industry leaders and members of the AWS Partner Network. 

“We cast a very broad net,” Jeff Kratz, AWS general manager for worldwide public sector partners, programs and sales, said in an interview. “Health equity is such a needed area for practical solutions,” Kratz said. The panel making the selections looked for unique solutions that have a market and considered startups’ culture and diversity, Kratz said. Learn more about this year’s cohort here. 

The 10 startups are: 

1. Clinify Health 

2. ClosedLoop.ai

3. CognitiveCare

4. Harmony Health

5. Kinetik

6. Pair Team

7. Samaritan

8. SameSky Health

9. Vincere Health

10. Zócalo Health

COVID-19 “accelerated many of the challenges of inequality in health,” Kratz said. It also accelerated how many web-enabled startups have cropped up to fill in gaps in care. This newer approach is preferred by many companies for its possibilities around security, reduction of costs in healthcare and accessibility, Kratz added. 

“We’re providing the tools and the access to the smallest startups to the largest healthcare institutions to hospitals and clinics and more, which is revolutionizing the healthcare market,” Kratz said of AWS. This accelerator is one way it hopes to boost ongoing innovation efforts.  

The program will kick off with an assessment of each startup based on its individual goals and how AWS can help achieve them, Kratz said. Then, the program will pull on experts to provide advice and training related to scaling, going to market and fundraising. Finally, startups will design their next steps, such as proofs of concept or pitches. 

Participants will get to experiment with AWS technologies and work with the likes of the Harvard T. H. Chan School of Public Health, Mass General Brigham, Philips and GE Healthcare. The program will conclude in the first-ever demo day at the AWS Healthcare Accelerator Pavilion at HLTH 2022 in November. 

The programs are a way for AWS to use the cloud to improve the healthcare system, the company says. The first U.S.-based AWS healthcare accelerator concluded in October 2021. Past cohort members reached a variety of goals through the program, Kratz said, including one participant landing a deal with Walmart Health and another being featured in Time. AWS separately has the Health Equity Initiative—a $40 million commitment meant to help advance health equity globally.

https://www.fiercehealthcare.com/health-tech/aws-announces-finalists-its-2022-health-equity-accelerator

Immatics finds a multi-tumor target for adoptive T-cell therapies

 Despite the hype around adoptive T-cell therapies, it’s still a challenge to find therapeutic targets that are consistent across tumor types and aren’t expressed in healthy cells. Now, a team of scientists from the University of Pennsylvania working with immunotherapy drug development biotech Immatics has identified an antigen component that checks both of those boxes.

In a study published Wednesday in Science Translational Medicine, the researchers reported their finding of a protein that when targeted through adoptive T-cell receptor therapy slowed cancer growth in mice. The protein was highly prevalent in tumor samples from patients with 11 different types of solid tumors but was rarely present in healthy cells, making it a prime potential target for T-cell therapies. Now, Immatics plans to pursue an investigational new drug application with the FDA in hope of launching a phase I clinical trial.

The team’s goal for its research was to find antigens that were present in different tumor types and could safely be targeted in T-cell therapies without harming other cells. They started by analyzing sets of normal and tumor tissue samples with Immatics’ XPRESIDENT discovery platform, which uses mass spectrometry to examine and compare hundreds of peptides across the immunopeptidome, or the ensembles of peptides associated with human leukocyte antigens. The XPRESIDENT analysis was paired with the company’s XCUBE bioinformatics approach, using artificial intelligence to quantify peptide copy numbers in each cell. 

“We detect and quantify what’s there and what makes the difference between cancer and normal,” Toni Weinschenk, co-corresponding author and Chief Innovation Officer at Immatics, explained in an email. In other studies, immune system peptides have been analyzed through binding predictions. But with Immatics' discovery platform and bioinformatics tools at their disposal, the team could take a quantitative approach. “We don’t have to predict,” Weinschenk said.

The scientists pinned down an antigen component that was highly expressed in cancer cells from multiple types of tumors but rarely in human tissue: an epitope encoded by exon 6 of the gene collagen type VI α-3, or COL6A3, which is produced from a tumor-specific alternative splicing event that rarely happens in healthy cells. The COL6A3 protein is a component of type VI collagen, which is present in connective tissue throughout the body, but exon 6 is expressed only in the stroma cells of the tumor microenvironment.  

“Protein collagen type VI alpha-3 (COL6A3) is abundantly expressed and therefore not selective enough to be targeted by adoptive cellular therapy,” Weinschenk said. “The tumor selectivity is based on a tumor-associated splicing event, which retains the target-encoding exon 6.”

With a target in their sights, the researchers set out to develop T-cell receptors, or TCRs, that would recognize the epitope without attacking other peptides. Again using data from Immatics' discovery platform to compare reactivity between tumor and normal cells, the team developed high-affinity TCR-T cells and injected them into mice that had been grafted with human leukemia cells. The cancer growth slowed, and the mice didn’t experience serious side effects.

To Weinschenk, the results show how the company's XPRESIDENT approach can be used not only to identify potential therapeutic targets but also to develop TCRs with strong safety profiles.

Next, Immatics plans to conduct more studies on the COL6A3 epitope to support its IND application with the FDA, though the company didn’t offer a timeline. If it were to move forward with a phase I trial, the new epitope would be the ninth product in the company’s pipeline on top of its programs with Genmab, GSK and Bristol Myers Squibb.

https://www.fiercebiotech.com/research/one-protein-many-cancers-immatics-finds-multi-tumor-target-adoptive-t-cell-therapies

Florida says FDA stalling on drug importation program in suit

 It’s Florida versus the U.S. Food and Drug Administration as the state’s quest to import cheaper prescription meds from up north has veered into court this week.

Florida is suing the U.S. drug regulator for allegedly dragging its feet on a Freedom of Information Act (FOIA) request linked to a drug importation program. Florida Gov. Ron DeSantis inked legislation on the issue back in June 2019.

The so-called Canadian Prescription Drug Importation Program aims to do what it says on the tin: bring cheaper medicines from Canada to the Sunshine State.

Florida is one of a handful of states angling to draw down cheaper medicines from Canada. Other states seeking permission to buy drugs from the Great White North include Colorado, Maine, New Hampshire, New Mexico and Vermont.

Back in 2020, then-President Donald Trump blessed a rule paving the way for such imports, though the measure has been met with opposition from industry heavyweights like the Pharmaceutical Research and Manufacturers of America. 

The trade group at the time voiced “grave concerns” about the drug import plan’s potential to expose people in the U.S. to “the dangers of counterfeit or adulterated drugs,” though its own lawsuit to block the Trump-era decision has since stalled, Endpoints News points out.

For its part, the FDA says it's "working to implement a statutory pathway for the importation of certain prescription drugs from Canada." 

Florida predicts the program could save local taxpayers up to $150 million a year once fully rolled out, according to a lawsuit filed Monday in Tampa Federal Court. The plan would start by importing drugs to treat HIV and AIDS as well as diabetes, hepatitis C and mental illness, the court documents state.

Florida says it’s “ready, willing, and able to begin operating the program immediately,” pointing out that it’s “already built” a refrigerated distribution center and locked in an approved importer and distributor that's currently on retainer for $1.2 million a month.

But Florida’s ability to kick off the import scheme is “stuck in the starting blocks” because the FDA must first approve the program, for which the state claims it submitted the required proposals back in November 2020.

“In the nearly two years while Florida’s [Section 804 Importation Program] proposal has been pending, the FDA has asked for several clarifications and supplements but has provided no outward evidence of substantive progress towards approving the proposal,” the Florida lawsuit states, adding that the “FDA has also refused to provide a timeline for the approval process.”

Because the regulator has allegedly been twiddling its thumbs, Florida’s Agency for Health Care Administration secretary, Simone Marstiller, submitted a FOIA request July 6 demanding multiple records related to drug importation proposals from Florida and other states.

Problem is, the FDA has not responded according to the deadline specified in the request, the state contends in its lawsuit against the regulator.

“Plaintiffs accordingly bring this suit to compel the FDA to respond to the FOIA request and provide the requested documents,” the court filing continues.

The 2020 Trump-era rule opening the door to Canadian imports came as part of the former president’s America First Health Plan.

Drug costs are lower in Canada because the country limits how much drugmakers can charge for medicines, Kaiser Health News explained in a September 2020 report. Nevertheless, the drug industry has long rallied against import efforts on the argument it could disrupt U.S. supply chains and ease the entry of unsafe or counterfeit medications onto the market.

Plus, market watchers have pointed out that Canada is a much smaller drug market than the U.S., so it wouldn't be able to supply cheaper pharmaceuticals on a large scale. 

Florida's would-be maneuver to dodge high U.S. drug costs comes as the Biden administration makes its own play at the long-standing issue via the Inflation Reduction Act. The bill, which President Joe Biden signed into law earlier this month, includes a number of drug pricing measures, which include giving Medicare the power to bargain for certain prescription drug costs. 

The bill is also set to cap per-patient out-of-pocket costs at $2,000 per year in Medicare and is expected to shift more responsibility for expenses beyond that limit onto payers. The biopharma industry also ardently resisted the Biden administration measures.

https://www.fiercepharma.com/pharma/florida-tees-legal-showdown-fda-over-stalled-information-act-request-canada-drug-import-plan

US plots move to private market in 2023, setting up market clash between Pfizer and Moderna

 The U.S. government expects to bow out of the distribution of COVID-19 vaccines and treatments, handing the countermeasures to the commercial market. And that bodes well for marketing expert Pfizer, the company argues.

No thanks to a lack of funds authorized by Congress, the Biden administration expects it won’t be able to continue buying COVID shots and therapeutics for free distribution starting next year, Dawn O’Connell, HHS’ assistant secretary for preparedness and response, said in a blog post Tuesday.

“We have always intended to transition this work to the commercial market and have been planning for that transition for some time now,” O’Connell wrote. “Unfortunately, the timeline to make the transition has accelerated over the past six months without additional funds from Congress to support this work.”

The government-led initiative has been offering vaccines and therapeutics to healthcare providers for free. And that will for sure change in the commercial setting.

The transition may not be a bad thing for COVID product manufacturers. Once the commercial market opens up, those biopharma companies will have access to more distribution channels and the ability to utilize additional marketing tools.

Before dropping out of dispatching vaccines and treatments, the U.S. government is ending a free at-home COVID test distribution program this Friday, citing lack of funding.

In terms of vaccines, HHS has secured about 171 million doses of bivalent, omicron-targeted boosters for this fall and winter. The FDA on Wednesday just authorized updated shots from Pfizer-BioNTech and Moderna. But starting from January 2023, HHS won’t have enough federal funds to support further distributions, O’Connell said.

As for therapeutics, the federal supply of AstraZeneca’s preventative antibody Evusheld is expected to run out in early 2023, followed by Merck’s oral antiviral Lagevrio by the second quarter at the latest. The HHS expects that its stock of Pfizer’s Paxlovid will be depleted by mid-2023

Gilead’s Veklury, the first COVID treatment approved, transitioned to the commercial market in October 2020 after a short period of federal government-managed distribution. Federal distribution of several COVID antibodies by Eli Lilly, Regeneron and GSK-Vir Biotechnology have been suspended because the drugs appeared to have lost potency against omicron.

ut Eli Lilly's bebtelovimab has retained its efficacy and FDA emergency use authorization. The company has made it available for purchase in the commercial market.

Meanwhile, developers of COVID products have been bracing themselves for the expected transition. Pfizer CEO Albert Bourla and Moderna chief Stéphane Bancel have both talked up their planning to have their products in the private market.

“As we look to 2023, we are prepared for a shift to the commercial market in the U.S. for COVID boosters, where the market will be more fragmented than it was during the pandemic where the U.S. government was the sole purchaser of vaccines,” Moderna chief commercial officer Arpa Garay said during an investor call earlier this month. Moderna has talked to commercial payers, distributors and key pharmacies about the transition, she added.

As Pfizer’s Bourla sees it, Pfizer can be “even more competitive” and its commercial skills are “even better suited” in an open market than a government-contracting model, he said during an investor call in July. Even before the pandemic, Pfizer was one of the world’s leading vaccine producers thanks to its pneumococcal vaccine Prevnar, whereas Moderna is a private commercialization greenhand. 

After moving to the commercial market, Pfizer will be able to reach “a much broader set of channels that we currently do today,” Pfizer’s biopharmaceuticals chief Angela Hwang said during the call.

In terms of consumer education, Pfizer has currently limited itself to unbranded disease awareness efforts, Hwang said. But in a commercial setting, branded education could focus on Pfizer’s products, including BioNTech-partnered Comirnaty and antiviral Paxlovid.

“All of these are things that […] the commercial organization of Pfizer does really well,” Hwang said “This is our sweet spot.”

https://www.fiercepharma.com/marketing/no-more-free-covid-vaccines-us-plots-move-private-market-2023-potential-boon-pfizer