After previously backing the startup, Edwards Lifesciences is exercising its option to acquire Innovalve and its mitral valve replacement implant.
In an SEC filing, Edwards said it plans to pay about $300 million in cash upfront, with the deal slated to close before the end of this year.
According to Innovalve, the company has received an FDA green light to conduct human feasibility trials in the U.S. using its Innostay system. The transcatheter implant is designed to form a tight seal within the mitral valve regardless of its natural shape, by twisting together and holding shut the valve’s tendon-like cords before deploying the prosthetic implant—a device that literally tugs at the heartstrings.
“Building on our learnings of the complexity of mitral disease, we know there is a need for a differentiated range of therapies for these patients,” Edwards’ transcatheter mitral and tricuspid therapy group leader, Daveen Chopra, said in a statement.
“Edwards’ SAPIEN M3 remains on track to become the first approved transfemoral TMVR system in Europe by the end of 2025,” Chopra added. “We believe the Innovalve technologies, paired with Edwards’ deep mitral expertise, will enable a TMVR platform that will expand the treatable population.”
Edwards first invested in Innovalve Bio Medical in 2017, as it was being spun out of Sheba Medical Center in Tel Aviv, Israel. Since then, Edwards said the company has shown “promising early clinical experience.”
The heart valve maker last week also invested in (PDF) the France-based mitral valve designer Affluent Medical, including 15 million euros to obtain options for its adjustable mitral ring and open-surgery valve implant, as well as an equity stake in the company.
Lantheus is expanding its holdings of PET imaging agents for Alzheimer’s disease, with the acquisition of Meilleur Technologies.
The deal grants Lantheus exclusive worldwide rights to Meilleur’s radiopharmaceutical diagnostic that highlights beta amyloid plaques in the brain. The injectable agent—known as NAV-4694, or F18-flutafuranol—is currently in phase 3 development.
The acquisition comes just days after the Centers for Medicare and Medicaid Services proposed a separate payment pathway for certain diagnostic radiopharmaceuticals and nuclear medicine imaging agents—instead of bundling them as part of the procedure, as it had in the past.
The change was put forward in CMS’ proposal for payment systems among hospital outpatient services and ambulatory surgical centers, set for the 2025 calendar year. Lantheus’ stock price jumped nearly 60% on the news.
The deal also follows the FDA’s approval earlier this month of Eli Lilly’s Kisunla (donanemab-abzt) treatment for Alzheimer’s, seen as a challenger to Biogen and Eisai’s Leqembi in a newly burgeoning area of anti-amyloid therapies.
“This acquisition solidifies our commitment to neurology, specifically for Alzheimer’s disease management, and reinforces our radiopharmaceutical leadership,” Lantheus CEO Brian Markison said in a statement, which pitched Meilleur’s NAV-4694 as a complement to the company’s PET agent MK-6240, aimed at Alzheimer’s tau tangles.
The companies estimate that nearly 12 million people are living with mild cognitive impairment or Alzheimer’s disease in the U.S. today, a number that may pass 20 million by 2050.
“With the combination of MK-6240 and NAV-4694, we are poised to provide important insights for guiding the use and assessing the impact of novel disease-modifying Alzheimer’s treatments,” Markison said. Lantheus previously acquired MK-6240, an F18-labeled agent also known as florquinitau, in February 2023 through its buyout of Cerveau Technologies.
While the exact financial terms of Lantheus’ deal with Meilleur were not disclosed, the companies said the stock purchase agreement includes an upfront payment as well as additional R&D and commercial milestones, plus royalties. Meilleur will also provide transitional clinical development services for a set time.
“We are excited by the potential of NAV-4694 for earlier identification of Alzheimer’s patients, empowering clinicians to select suitable candidates for timely therapeutic interventions,” said Meilleur CEO Rick Hiatt. “With Lantheus’ expertise in radiopharmaceutical diagnostics and ability to scale operations, I am confident that Lantheus is the ideal company to bring this late-stage biomarker through pivotal trials and into commercialization to one day benefit patients at risk of Alzheimer’s disease.”
Russia’s state-runRossiya1 TV channel ran a segment on Sunday evening which appeared to be in direct reaction to the US recently announcing it plans to placelong-range missiles in Germany.
The segment included the Russian pundits ominously warning that Russian missiles can strike European capitals. "Almost all European capitals will be under threat if our missiles are stationed in Kaliningrad: Berlin, Warsaw, all the Baltic states, Paris, Bucharest, Prague, and of course, the American bases in Germany," TV host and State Duma lawmaker Yevgeny Popov said. Watch the Russian-language segment below:
"Special attention to Britain, our traditional enemy…Britain is in the most vulnerable position — basically, three missiles are enough and this civilization will collapse," Popov added.
At the same time, the show presented a map of Europe, showing potential target areas. UK and Europe-based news outlets picked up on the threat and featured commentary on the segment.
The US had announced last Wednesday in relation to the NATO summit in Washington that week: "The United States will begin episodic deployments of the long-range fires capabilities of its Multi-Domain Task Force in Germany in 2026, as part of planning for enduring stationing of these capabilities in the future."
"When fully developed, these conventional long-range fires units will include SM-6, Tomahawk, and developmental hypersonic weapons, which have significantly longer range than current land-based fires in Europe," the statement posted to the White House website added.
The major development had prompted Kremlin spokesman Dmitry Peskov to respond: "Europe is a target for our missiles, our country is a target for U.S. missiles in Europe." He explained further, "We have enough capacity to contain these missiles but the potential victims are the capitals of these countries."
"Europe is coming apart. Europe is not living its best moment. In a different configuration, a repeat of history is inevitable," he said while looking back to the Cold War.
If Donald Trump takes the White House after November, it will be interesting to see whether he sticks by Washington's proposed ultra-provocative missile expansion plans, or if he halts it while desiring to deescalate tensions over arms placement with an aim of of finding Ukraine peace.
The long list of unfamiliar names on ingredient labels of processed foods is already a cause for concern. However, many people are unaware of another category of additives never listed on these labels. These “invisible” additives are known as processing aids.
Processing aids serve various roles in food production. They can soak and wash ingredients, filter beverages like wine or juice to make them clearer, or improve the texture of bread to make it softer and more elastic. During the production process, these aids are consumed, transformed, or removed, rendering them virtually undetectable in the final product.
Take fruit juice as an example. Using enzymes for juice extraction is a common production method, which can result in juice yields exceeding 90 percent of the fruit’s weight. By treating the raw fruit materials with several enzymes at a specific temperature for a few hours, the fruit “liquefies.” Specifically, cellulase breaks down the cell walls of the fruit, releasing more juice and sugars, while pectinase and amylase break down polysaccharides such as pectin. These enzymes improve the flow of the juice in processing containers and enhance its sweetness. They are consumed and transformed during processing, ultimately not appearing on the ingredient label.
Another example is regular milk supplemented with lactase, which becomes low-lactose milk, whereas adding rennet turns it into cheese. Additionally, applying palm wax to baking molds aids in easy cake release. Bottled sauces often have nitrogen added during bottling to displace oxygen, preventing oxidation and product spoilage.
Processing aids include a variety of substances used in food production, including clarifying agents, clouding agents, catalysts, flocculants, filter aids, and crystallization inhibitors. These aids perform essential functions such as improving texture, enhancing clarity, and preventing spoilage.
Some people might worry, as these substances are not stated on the label, Martin Bucknavage, a senior food safety specialist at Penn State University’s Department of Food Science, told The Epoch Times. However, he said that there is no need for excessive concern.
“There [are] risks in all processes; there [are] definitely potential side effects and negative aspects that need to be looked into,” Tim Bowser, the food process engineer at the Robert M. Kerr Food and Agricultural Products Center at Oklahoma State University, told The Epoch Times. Yet unlike additives, the nature of processing aids determines that “they do not have that ability to cheat” and are less likely to be used for deception and adulteration.
In real-life scenarios, “the residuals would be too low to detect,” Mr. Bowser said.
However, he noted that with the continuous development of detection technologies, some companies are now capable of detecting substances at levels as low as parts per billion or even trillion. Furthermore, the safety of processing aids is constantly being evaluated, and as people’s understanding grows, regulations governing their use may be adjusted, or “something could be removed from the generally regarded as safe list.”
Alcohol, Juice, and Heavy Metals
Despite Germany’s stringent centuries-old laws governing beer production methods, routine analyses have uncovered a gradual increase in arsenic content in German beer, with diatomaceous earth being considered a potential source.
Diatomaceous earth is commonly used to filter alcohol and beverages to increase their yield.
To test this hypothesis, researchers mixed diatomaceous earth with beer and analyzed the filtrate for trace metals, finding elevated levels of arsenic and aluminum.
Diatomaceous earth is a fossilized sedimentary deposit formed from the cell walls of ancient diatoms that settled on the ocean floor. After extraction, it is ground into a powder and primarily composed of silicon dioxide.
Another often-used beverage filter during the manufacturing process is bentonite, a clay with adsorption capabilities, which the FDA classifies as “generally recognized as safe.”
Since diatomaceous earth and bentonite are derived from mined materials, “they can contain a large array of elements, including heavy metals,” wrote Benjamin W. Redan, a U.S. Food and Drug Administration (FDA) scientist, in a 2020 study published in the Journal of Agricultural and Food Chemistry.
A study conducted by the FDA and the University of Maryland researchers indicated that diatomaceous earth can increase arsenic levels in apple juice by more than five times, while arsenic levels in grape juice increased by 67 percent.
Additionally, researchers have discovered that adding bentonite can increase vanadium levels in apple juice from around 3 μg/kg to up to 200 μg/kg. While this does not reach toxic levels, the increase is notable.
The quality of different processing aids varies. In January 2023, Hungarian researchers published a study in the journal Foods. They added 21 types of commercial bentonite products to white wine and found that while some showed no significant change in lead content, others increased considerably. For instance, one type of bentonite increased the lead content from 2.27 µg/L to 9.46 µg/L, marking a rise of over 300 percent.
“The use of certain processing aids can increase levels of contaminants in beverages,” the FDA spokesperson told The Epoch Times. “The FDA has issued draft guidance that notes that changing or treating filter aids may reduce contaminants released during filtration,” he added.
Hidden Concerns of Decaffeinated Coffee
A processing aid called methylene chloride is employed to remove caffeine from coffee beans, producing decaffeinated coffee.
Methylene chloride is a highly efficient solvent but is often considered hazardous. In the liver, it metabolizes to produce significant amounts of carbon monoxide and formaldehyde, the latter being a known carcinogen. In animal models, methylene chloride has shown hepatotoxicity, neurotoxicity, and potential carcinogenic effects.
The FDA regulations specify that the residue level of methylene chloride in food must not exceed 10 parts per million (ppm), which is equivalent to 10 mg/kg or 10,000 μg/kg.
While methylene chloride’s high volatility generally facilitates the removal of its residues, they can still persist, and residues in some products may be relatively high.
Considering that decaffeinated coffee is a preferred choice for sensitive groups such as pregnant women, people with cardiovascular diseases, and those with neurological conditions, some people have raised concerns about the use of methylene chloride in its production.
The nonprofit organization Clean Label Project, which has long focused on the coffee industry’s use of methylene chloride in producing decaffeinated coffee, commissioned a professional analytical company in 2022 to conduct a double-blind test on 17 decaffeinated products. The results showed that although all products had methylene chloride levels below the FDA’s set standards, one product contained 8,931 μg/kg, close to the upper limit, while two other products had residue levels between 3,500 and 4,000 μg/kg.
“Anything that’s used like that, that is known to be [a problem] should be continuously looked at,” Mr. Bowser said when discussing the use of methylene chloride in the production of decaffeinated coffee. He emphasized that if a substance is deemed hazardous, it remains dangerous, regardless of the residual amount.
Mr. Bowser also underscored the importance of ongoing scrutiny and openness to diverse perspectives regarding certain widely used substances currently considered safe, such as hexane used in soybean oil extraction.
Hexane and Vegetable Oil
Traditional mechanical pressing methods for extracting vegetable oil typically achieve extraction rates ranging from 60 to 80 percent for oilseed crops. In contrast, chemical solvent extraction, which is now predominantly used, can achieve rates close to 100 percent.
Hexane, a commonly used solvent in this process, is a hydrocarbon extracted from crude oil. It remains liquid at room temperature but is highly volatile.
In the extraction of vegetable oils such as canola, sunflower, and cottonseed, the oilseeds undergo cleaning, crushing, steaming, and drying before being immersed in hexane. Following the principle of “like dissolves like,” lipids from the seeds are released, while hexane is subsequently evaporated using hot steam. The extracted oil then undergoes further refining processes, while hexane is collected and reused.
Hexane is also employed in the extraction of flavors, color additives, and other bioactive ingredients in addition to vegetable oils.
Numerous studies have identified hexane as neurotoxic to humans. According to the U.S. Environmental Protection Agency (EPA), short-term exposure to hexane can cause irritation, headaches, and dizziness, while prolonged exposure can lead to nerve damage.
The EPA has set a reference dose (RfD) for hexane exposure based on animal toxicity studies, establishing a daily limit of 0.06 mg/kg/day for humans. For a person weighing 70 kilograms, this provisional reference dose equates to a maximum of 4.2 milligrams per day. The European Medicines Agency classifies hexane as a Class 2 solvent, meaning it should be limited, and has established a “Permitted Daily Exposure” similar to that of the EPA.
Different countries have varying regulations regarding hexane residues in edible oils. For example, the European Union’s standard is 1 mg/kg. Some vegetable oils in developing countries have been found to exceed the EU’s hexane residue limit. From an environmental perspective, although most hexane is recovered during the production process, some is still released into the air and can enter the food chain. Recent estimates indicate that an additional one million tons of hexane are needed globally each year to compensate for losses during the extraction process.
The FDA currently has no regulations regarding hexane residue levels in edible oil products. “To ensure that vegetable oil is sufficiently purified to minimize levels of contaminants like hexane, manufacturers may set a limit that only allows for trace amounts of hexane in the final product.” The FDA spokesperson told The Epoch Times, “The FDA does not typically sample vegetable oils for residual hexane ... based on the information that we have, any residual levels would be very low, if detectable if added to food.”
Driven by concerns about hexane as an extraction solvent, some processors are shifting towards healthier extraction methods. These methods include aqueous-assisted enzyme extraction, natural solvent extraction (such as from citrus peel and tree oils), and more advanced mechanical pressing methods with higher oil yields.
Enzymes in Bread: A Seemingly Harmless Aid
There is another major category of processing aids: enzymes, widely utilized in baking products such as bread.
Xylanases have been employed in baking for several decades. They degrade polysaccharides in flour, resulting in fluffier bread. Proteases break down large protein molecules in the dough into smaller ones, making the dough softer and more malleable. They also expedite dough fermentation, enhancing the texture and flavor of bread. Additionally, by breaking down more proteins into amino acids, proteases enrich the nutritional value of bread and facilitate absorption. Alpha-amylase (α-amylase) breaks down starch in the dough into sugars, improving the softness, elasticity, and sweetness of the bread. Additionally, it reduces moisture content in bread and regulates microbial growth, thereby extending its shelf life.
While patent cliffs are looming for many of biopharma’s top-selling products, the industry has enormous capacity to respond as “conditions for M&A are favorable,” according to a research note from Morgan Stanley.
In the July 11 report, the analysts calculate that products losing exclusivity through 2030 are generating a combined $183.5 billion in annual sales, with Amgen, Bristol Myers Squibb and Merck facing the most exposure of their revenue.
Meanwhile—citing company financial reports and data from Visible Alpha and FactSet—Morgan Stanley estimates that Big Pharma has $383.1 billion of firepower available for dealmaking. The companies sitting on the most dry powder are Johnson & Johnson, Merck and Novo Nordisk, the analysts said.
"We continue to see the conditions as generally favorable for bolt-on M&A as large-cap pharma companies have balance sheet capacity and a need to acquire outer-year revenue," the Morgan Stanley team, led by Terence Flynn, Ph.D., wrote.
Per Morgan Stanley’s metrics, J&J is in excellent shape as just 33% of its revenue is exposed to patent expirations through 2030, compared to an industry average of 38%. Other biopharma companies in good positions regarding their patent cliffs are Vertex (6%), Gilead (24%), AbbVie (29%), Eli Lilly (31%) and Pfizer (33%).
At the other end of the list, Amgen has the most revenue at risk at 67%, with its top four products on the clock. Bone cancer drugs Prolia and Xgeva, which combined for sales of $6.1 billion last year, are due for patent expirations over the next two years. Enbrel ($3.7 billion) and Otezla ($2.2 billion) also are set to lose exclusivity by the end of the decade.
Amgen, of course, has already taken a major step in addressing the patent cliff with its $27.8 billion acquisition of Horizon, which was completed in October and brought potential blockbusters in Tepezza for thyroid eye disease, Krystexxa for gout and Uplizna for a rare neurologic disorder.
Next on the patent cliff exposure list is BMS, with 63% of its revenue at risk. Blood thinner Eliquis, which generated $12.2 billion last year, and cancer drug Opdivo ($9 billion) are on the clock in the next few years while another cancer treatment, Revlimid ($6.1 billion), has already lost its U.S. exclusivity.
BMS also has addressed its cliff, acquiring Karuna, Mirati and RayzeBio in a three-month splurge at the end of 2023. Last month, BMS CEO Chris Boerner said that the company’s still scouting out deals.
"Despite these transactions, there remains significant LOE exposures for many of these companies," the analysts wrote. "Further, uncertainty related to the FTC's approach to pharma transactions, which we believe may have impacted deal appetites in the 2022-2023 period, seems to have largely subsided at this point following the closure of larger transactions in recent months."
It’s no surprise that Merck is on the list, with 56% of its revenue exposed to patent expirations. Most of that comes from mega-blockbuster cancer drug Keytruda, which generated $25 billion in sales last year, accounting for 42% of the company’s total haul. Keytruda is set to lose its exclusivity in 2029.
"Merck continues to have the combination of need to offset the Keytruda LOE and meaningful balance sheet capacity," the Morgan Stanley analysts wrote. "AbbVie, BMS and Pfizer have all recently transacted, so we see these companies as more likely to be acquirers over the medium term."
It's no secret that cell and gene therapies have faced manufacturing hurdles as the advanced medicines have become increasingly popular in recent years. Now, the FDA is proposing to work directly with industry through a series of facility tours that could enable both sides to learn something from each other.
In a federal register post Monday, the Office of Therapeutic Products (OTP) of the FDA’s Center for Biologics Evaluation and Research (CBER) unveiled its Cellular and Gene Therapies Interactive Site Tours Program. The initiative is designed to let CBER project managers and reviewers swap regulatory know-how with their industry counterparts on-site.
CBER hopes the program will bolster its review skills by providing agency staffers with a better understanding of the biotechnology manufacturing industry and its operations, according to the post.
The goal of the program, which cell and gene therapy manufacturers are being invited to volunteer for by August 14, is twofold: grant CBER and OTP staffers “firsthand exposure” to the industry’s product development processes; and create a venue for sharing information about project management best practices with industry representatives.
Ultimately, the final program will likely only last for a few days, according to the FDA. While it’s running, a small group of OTP regulatory project managers and reviewers will be able to observe operations and biologics manufacturing or packaging facilities, plus pathology and toxicology labs and regulatory affairs operations.
The FDA staffers and their industry counterparts will also be able to take part in workshops focusing on “selective regulatory issues” important to both parties, the agency said.
Given the sensitive nature of the FDA’s work and its relationships with those in the industry, the regulator stressed that the site tour and program is in no way meant to inspect, assess, judge or perform a regulatory function.
The sites the FDA picks will ultimately come down, in part, to the agency’s available resources. Additionally, for a cell and gene therapy manufacturer to qualify for the program, their facility must be in good standing with the U.S. drug regulator.