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An ADC specialist sinks on safety concerns for blood cancer drug

ADC Therapeutics said its blood cancer drug met the main goal of a confirmatory trial, but the experiment recorded more deaths among patients treated with the drug, sending shares down more than 50% Thursday morning. The Switzerland-based company unveiled data

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ADC Therapeutics said its blood cancer drug met the main goal of a confirmatory trial, but the experiment recorded more deaths among patients treated with the drug, sending shares down more than 50% Thursday morning. The Switzerland-based company unveiled data from its Phase 3 trial testing an antibody-drug conjugate called Zynlonta in combination with the medicine rituximab among people with a type of hard-to-treat blood cancer. The pairing extended progression-free survival in trial participants compared to a standard treatment combination, meeting the study’s primary endpoint. But the results were overshadowed by the number of deaths in the study, leaving investors to question the drug’s chances of gaining full approval. The Food and Drug Administration granted accelerated approval to Zynlonta in 2021 based on the results of a trial in which it wasn’t compared to a placebo. “Given other available options to patients,” the number of deaths “may be difficult to accept for physicians, patients and regulators,” wrote RBC Capital Markets’ analyst Leonid Timashev in a note Thursday. Zynlonta, used to treat large B-cell lymphoma in people whose disease hasn’t responded to at least two treatments, is ADC’s only asset. The Phase 3 trial paired the drug with rituximab and tested it against an immunotherapy cocktail of rituximab plus the chemotherapy drugs gemcitabine and oxaliplatin across 440 participants. ADC’s treatment extended progression-free survival by 1.4 months, with enrollees receiving Zynlota surviving 6.1 months without progression compared with 4.7 months for those on the immunotherapy regimen, a statistically significant difference. The company did not meet its secondary endpoint for overall survival, but said there was “no detrimental effect” on that measure. However, 27 deaths were recorded for those given Zynlonta, compared to the nine deaths recorded for the immunotherapy arm. The company noted a majority of deaths occurred in patients aged 75 years or older. Eric Schmidt, from investment firm Cantor Fitzgerald, wrote in a client note that while the death total is likely to “temper both investors' and physicians' views towards these results,” there are some explanations for why the rate was higher than what was previously seen for Zynlonta. Schmidt explained that the Phase 3 trial included deaths up to 105 days after treatment, compared to a previous trial that recorded events up to 30 days. Additionally, he argued it’s “worth noting that most of these events” occurred in elderly patients, with a high portion of them having “advanced, aggressive disease and poorer overall health.” Based on the data, ADC plans to meet with the FDA in August to discuss next steps. It is preparing for a regulatory submission in the fourth quarter. Analysts such as Timashev, though, remain unsure of the drug’s future. In his note, Timashev wrote that while the trial did win on progression-free survival, the “benefits were modest, with no clear overall survival trend, and the significant death imbalance makes the benefit/risk profile difficult to accept and adds considerable regulatory risk.” Others still remain bullish. Schmidt wrote that “despite the safety hiccup, management expressed confidence in the regulatory path.” “We believe these data will support conversion from accelerated to full FDA approval,” he added.

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Dr. Harrison and Finnish neuroscientist Dr. Miia Kivipelto explore the complex interplay between genetics and lifestyle in Alzheimer's development. Learn how the groundbreaking FINGER study demonstrates potential prevention strategies, and discover the latest evidence on how environmental factors, diet, and chronic conditions influence Alzheimer's risk.

Source: www.biopharmadive.com ↗
02What the Artificial Neuron Cannot Do

Hersam’s next goal is a small circuit — perhaps 10 artificial neurons — where each one fires differently, and together they accomplish what would require thousands of conventional transistors. “ Silicon achieves complexity by having billions of identical devices,” Hersam said. “The brain is the opposite. It’s heterogeneous. The complexity is at the device level.” But Gaudet sees a gap no circuit design can yet fill: Biological neurons grow new connections and prune old ones, strengthening pathways that are used and weakening those that aren’t. Hersam’s lab’s printed neurons — or any other neuromorphic technology that mimics neuronal dynamics — can’t achieve that level of complexity yet. Brown is careful about the distance remaining between these printed neurons and the real thing. “Neurons are just so flexible,” he said. “They can totally change what they’re doing based on whether they’ve learned something and based on your emotional state. There’s a lot of hidden mysteries.” Sangwan suspects the device has more to reveal. “It’s a nonlinear dynamical system,” he said. “We don’t fully know how many different variables you need to explain it. It’s just the beginning.” Hersam, Sangwan, Brown, Holla, and Gaudet reported having no relevant financial disclosures. Disclosure information for study authors is available in the original study publication.

Source: www.medscape.com ↗
03China: Threat or opportunity?

One of the biggest biotech news stories of recent years is China’s continued rise as a biotech and life sciences powerhouse. China conducts a quarter of all clinical trials and drug development and has almost 1,500 new drugs in development.¹ Many China-based biotechs have benefitted from government funds, out-licencing deals with large pharmas and venture capital funding. However, policymakers in the US and EU have concerns about the possible threat to their region’s biosecurity and competitiveness as centres for health and life science research. Given China’s increased importance, ICON Biotech conducted the same biotech sector survey with 100 China-based biotech leaders. The results show that Chinese biotechs face many of the same challenges as biotechs located elsewhere. They share the same funding challenges and burdens associated with increasingly complex clinical trials and regulations.

Source: www.biopharmadive.com ↗
04What Comes Next

With data expected in the fourth quarter of 2026, we are prioritizing histology alongside patient-reported outcomes using the Celiac Disease Symptom Diary, one of only two instruments developed in line with U.S. Food and Drug Administration (FDA) guidance, to capture changes in symptoms such as abdominal pain and nausea. Ultimately, the broader aim is to give gastroenterologists and patients a therapeutic option for a disease that has long been managed without one. The future of drug development will not be defined by statistical significance alone, but by whether new therapies also improve the daily burden of living with celiac disease. “The first therapy to cross the line could change the field,” Geller concluded. “It would help establish celiac as a serious medical condition with options beyond a restrictive diet and open the door for what comes next.” Dr. Paul Lizzul is chief medical officer at First Tracks Biotherapeutics, a clinical ‑ stage biotechnology company advancing antibody therapeutics that modulate immune pathways implicated in autoimmune and inflammatory diseases. Marilyn Geller serves as an advisor to First Tracks Bio. Footnotes Abadie V, Jabri B. IL-15: a central regulator of celiac disease immunopathology. Immunol Rev . 2014;260(1):221-234. https://doi.org/10.1111/imr.12191. Yokoyama S, Watanabe N, Sato N, et al. Antibody-mediated blockade of IL-15 reverses the autoimmune intestinal damage in transgenic mice that overexpress IL-15 in enterocytes. Proc Natl Acad Sci U S A . 2009;106(37):15849-15854. https://doi/full/10.1073/pnas.0908834106. Anthony S, Schluns KS. Emerging roles for IL-15 in the activation and function of T-cells during immune stimulation. Research and Reports in Biology . 2015;6:25-37. https://doi.org/10.2147/RRB.S57685.

Source: www.biopharmadive.com ↗
05Why Muscle Cells Might Do Some Heavy Lifting

Brown was studying gene therapy in the 1990s when he designed a technology to turn mRNA expression on or off in different cells. For the new mouse study, published in Nature Biotechnology , he adapted the technology to turn off mRNA expression in dendritic cells, muscle cells, or liver cells. The researchers then vaccinated the mice with each version, delivering the vaccines both intravenously and intramuscularly. “The results were pretty stunning,” Brown said. When mRNA expression was turned off in muscle cells, T-cell response went down, suggesting muscle cells play a role in immunity. When expression was turned off in liver cells, T-cell expression tripled — indicating liver cells dampen immunity. Turning off expression in dendritic cells had no effect on T-cell activation, though it did reduce the number of killer T cells by as much as half. (Interestingly, no such reduction occurred when the antigen was SARS-CoV-2 spike. Brown is now investigating why different antigens had varying effects.) Knowing all this is crucial for designing effective mRNA vaccines and therapies. That’s because different mRNA therapies require different strategies. Cancer vaccines must boost tumor-fighting killer (CD8+) T cells. For genetic disease treatments, scientists want to avoid triggering the immune system to prevent killing the very cells the mRNA is meant to modify. “Understanding the immunology is extremely important for this class of drug,” Brown said. The finding doesn’t mean dendritic cells aren’t important for mRNA vaccines to work. “It just means that the mRNA doesn’t have to get into those cells to induce an immune response,” Brown said. Instead, the antigen can be transferred to those dendritic cells.

Source: www.medscape.com ↗
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