Ari VanderWalde

Policy Update Alert 🚨 In a great step toward alignment with NCCN guidelines, ASCO guidelines, FDA labeling and clinical study evidence, United Health Care medical policy for #biomarker testing via ctDNA/Blood-based FDA-approved Companion Diagnostics #comprehensivegenomicprofiling has been UPDATED to allow: 1) Repeat testing at progression/recurrence up to 3 times a year 2) ctDNA (#liquidbiopsy) testing no longer requires tissue insufficiency/infeasibility to be demonstrated. 3) Concurrent testing (tissue and #ctDNA within 30 days of each other) is explicitly allowed for NSCLC and breast cancers Take-home points: 1) 3x per year seems like a great start for health plans worried about serial testing outside of progressive disease. This can be handled through policy or claims edits with a frequency flag. Many #utilizationmanagement techniques can address such concerns. 2) Concurrent testing is commonly practiced in advanced cancers. Due to the time considerations and heterogeneity, both tissue and ctDNA testing can identify unique biomarkers- neither is 100% sensitive. NCCN guidelines for #NSCLC and #Breast cancer include such discussions of concurrent/complementary testing.... if we want broader payer adoption, it will need to start with NCCN. 3) While policy changes take time, this is a nice example of steady expansion and considerations of guidelines and evidence over time. Huge kudos to the UHC policy teams!

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Excited to share the news of the closing of a 207.5 million Series C financing of Aviceda Therapeutics that will support the fully enrolled 300 patient Phase 2b/3 trials evaluating AVD-104 compared to active control. AVD-104 is a a glycomimetic that reprograms microglia/macrophages to their neuroprotective and resolution state while activating Complement factor H (CFH) to deamplify the alternative complement pathway. AVD 104 - halts macrophage phagoptosis of viable retinal cells ( RPE and Photoreceptors), prevents pathologic complement opsonized phagocytosis, restores photoreceptor protective microglial function, and potentially stops CD163+ macrophage induced synaptic deficits. Clinically this multimodal mechanism stops retinal loss, restores retinal function, and potentially improves vision in patients with dry macular degeneration and geographic atrophy. This molecule has the potential to be first in class, best in class treatment for geographic atrophy, the blinding age related, late stage complication of macular degeneration.

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Long-term Safety of Gene-Modified T Cell Therapy: New Insights from a Large Cohort Study I must admit that throughout my career I’ve been surprised by the low frequency of insertional mutagenesis after gene modification of T cells. I was a postdoc working at the NIH in 1990 when the first patient was dosed with gene modified cells. It seemed outrageous to many in the community then ... and fears persist. That's because gamma retroviruses and lentiviruses randomly integrate into the genome, usually in or near expressed genes. Despite differences and improvements in newer vectors, both can cause aberrant gene expression—upregulation, downregulation, or dysregulation—via genetic or epigenetic mechanisms. * Each gene-modified T cell product can contain 10’s of thousands of integration sites, so naturally scientists worry about knocking out tumor suppressor genes (like p53) or activating proto-oncogenes (eg MYC). * What surprised so many over the past 35 years is that the predicted disasters of malignant transformation of T cells simply were not frequently observed. Gene modified T cells, like CAR-T cells, have helped thousands of patients in recent years, and this number that is rapidly increasing with new applications like treating autoimmune disease. This week, Carl June, Joseph Fraietta, Frederic Bushman Lab, and colleagues published a comprehensive analysis of 783 patients with over 2,200 patient-years of follow-up. Here's what they found: -> Secondary Malignancies: 18 cases (2.3%) were identified, with a 5-year incidence of 4.2%. Importantly, there was NO EVIDENCE of vector-mediated insertional mutagenesis, reinforcing the safety of gene-modified-T cell therapy. Persistent immunodeficiency and infections remain common long-term challenges, but rates appear to decline over time. Factors like lymphodepleting chemotherapy, genetic predispositions, and prior treatments may contribute to secondary malignancies and immune-related complications. These findings underscore the relative safety of gene-modified T cell-based therapy. There are areas for improvement, and novel strategies are already in development to enhance both safety and efficacy. https://lnkd.in/ewJA2s4s This work highlights the importance of continuous monitoring and innovation in immunotherapy. Together, let’s advance the frontier of engineered T cell therapies to bring safer, more effective treatments to patients. #Immunotherapy

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It was a pleasure speaking with Targeted Oncology about the FDA’s draft guidance on radiopharmaceutical dosing released earlier this year. In this short video, I share why an FDA-informed perspective is critical when interpreting and applying new guidance for industry. This guidance reflects a major step forward in how the agency is thinking about radiopharmaceuticals, recognizing that these therapies are fundamentally different from external beam radiation and deserve their own framework for dose justification and safety monitoring. These documents outline expectations, but understanding where there is appropriate flexibility, and how to leverage that based on the science, is where real progress happens. That’s where having someone who’s been on the other side of the table matters. Someone to help read between the lines, anticipate regulatory perspectives, and help developers engage FDA with confidence. Watch the full interview for more insights on what this guidance means for radiopharma. Precision For Medicine #Radiopharmaceuticals #FDAGuidance #RegulatoryScience

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Exciting news on the horizon! Ashvattha Therapeutics, led by Arshad M. Khanani, is set to unveil groundbreaking Phase 2 data for patients dealing with Diabetic Macular Edema (DME) and Age-Related Macular Degeneration (AMD). The forthcoming results promise to revolutionize treatment approaches, offering patients a convenient monthly subcutaneous therapy akin to GLP-1s. This innovative approach not only reduces the necessity for eye injections but also alleviates the treatment burden for both patients and physicians. Moreover, the therapy showcases dual benefits by extending its positive impact to both eyes of individuals with bilateral disease, a unique feature setting it apart from other available options. Stay tuned for a comprehensive overview post-presentation to delve deeper into the transformative implications of this data release. For more insights, check out the detailed release post-presentation: [Link to the news release](https://lnkd.in/ggjr-_uT)

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JUST RELEASED: Our 2024 Scientific Report contains original manuscripts and whitepapers based on our research partnerships and recent policy initiatives. Key Topics: · Real-World Evidence from Clinical Practice · Innovative Drug Development & Advancing Early Endpoints · Harmonizing Biomarker Measurement & AI Applications 2024 Scientific Report: https://lnkd.in/eYsP7s9u We hope this resource will provide unique insights and inform future oncology drug development, legislative and regulatory policy, and patient care. Thank you to all of our collaborators that help drive this work forward!

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