EGFR positive Adenocarcinoma of Lung

Study designed to explore novel markers for identifying responders with immune checkpoint inhibitors in patients resistant to targeted therapies WALTHAM, Mass.--(BUSINESS WIRE)-- BostonGene, a leading provider of AI-driven molecular and immune profiling solutions, and Saga University located in Saga, Japan and known for its commitment to educating and training researchers and professionals in the medical and healthcare fields, announced today the launch of a collaboration aimed at discovering biomarkers for immunotherapy (IO) treatment response and treatment-related toxicity in advanced non-small cell lung cancer (NSCLC) patients. This press release features multimedia. View the full release here: EGFR-TKI treatment effectively targets EGFR mutation-positive NSCLC. Still, acquired resistance often leads to recurrence within 1 to 2 years, presenting a challenge for post-treatment optimization. Immune checkpoint inhibitors (ICIs) are standard therapy for NSCLC, but the efficacy in EGFR mutation-positive cases is limited. However, combination therapy with ICIs and anti-angiogenic agents has shown promise in EGFR-positive lung cancer. This study will evaluate the tumor microenvironment (TME) utilizing the BostonGene Tumor Portrait™ test in tissue samples collected before EGFR-TKI treatment and before ICI administration in patients with EGFR-positive lung adenocarcinoma. The study aims to examine the relationship between TME characteristics and the effectiveness of ICIs in these patients and investigate TME changes resulting from EGFR-TKI therapy. Furthermore, researchers will review cases where small-cell transformation occurred as a mechanism of EGFR-TKI resistance, aiming to elucidate the molecular mechanisms underlying this transformation within the TME context. By addressing these objectives, we enhance our understanding of TME dynamics and its implications for treatment response, ultimately informing improved therapeutic strategies for EGFR-positive lung adenocarcinoma. “We are dedicated to advancing medical research directly impacting patient care. By partnering with BostonGene, we aim to uncover novel biomarkers to revolutionize how we approach immunotherapy treatment in EGFR-positive lung cancer, ultimately improving patient outcomes,” said Dr. Naoko Aragane, Professor of Saga University. “Our collaboration with Saga University underscores our dedication to advancing the standard of care in Japan by bringing novel technologies to the region. The study marks an opportunity to delve deep into the complexities of the tumor microenvironment in EGFR-positive lung cancer patients, equipping oncologists with more targeted and effective immunotherapy strategies for their patients,” said Nathan Fowler, MD, Chief Medical Officer at BostonGene. BostonGene, NEC Corporation and Japan Industrial Partners established BostonGene Japan Inc., a joint venture leveraging BostonGene's advanced molecular technology and NEC's biocomputational algorithms in 2023. The company aims to deliver its industry-leading personalized tests to cancer patients in Japan and collaborate with academic and industry partners to accelerate the development of targeted therapies. About BostonGene Corporation BostonGene has a mission to provide transformative, AI-integrated molecular analytics and biomarker discovery for precision matching of therapies to improve the lives of patients living with cancer and other immune-related diseases. BostonGene’s concierge-service model provides customized client solutions using a multi-omic approach prioritized for real-world impact to optimize standard-of-care therapies, accelerate research and provide cost-effective, measurable data-driven results. BostonGene’s tests reveal key drivers of each patient’s unique disease profile, including an in-depth pro the immune microenvironment, actionable mutations, biomarkers of response to diverse therapies, and recommended therapies. Through these comprehensive analyses, BostonGene’s tests generate a personalized roadmap for therapeutic decision-making for each patient. For more information, visit BostonGene at .

Thanks to the FDA approval, Takeda said it’s looking to reverse a previous impairment loss tied to Eohilia’s FDA rejection in 2021. Eohilia, an oral suspension formulation of the corticosteroid budesonide, has surprisingly won over the FDA even after the drug’s developer, Takeda, had at one point abandoned the program following an FDA rejection. Monday, Takeda announced the FDA’s approval for Eohilia for treating people 11 years and older with the inflammatory disease eosinophilic esophagitis (EoE). This makes Eohilia the first FDA-sanctioned oral med for the condition. In 2022, Sanofi and Regeneron’s injectable Dupixent claimed the title as the first FDA-approved therapy for EoE. “As the treatment needs and goals of patients with EoE can vary, I welcome the flexibility that Eohilia offers as an oral medication,” Ikuo Hirano, M.D., from Northwestern University, an investigator in Eohilia’s clinical trials, said in a statement Monday. Eosinophilic esophagitis is a chronic inflammatory disease that can cause painful damage to the esophagus, resulting in difficulty in swallowing. The condition affects about 1 in 2,000 people in the U.S., and Takeda has estimated Eohilia could reach $300 million to $500 million in peak sales. Eohilia’s approval comes after some twists and turns. After a regulatory delay caused by additional data submissions, the FDA in late 2021 handed Takeda a rejection, blighting Eohilia’s prospect of becoming the very first official EoE drug. After reviewing the FDA’s complete response letter, Takeda realized that the agency wanted data from an additional clinical trial, and that it could not take the drug any further. “After a deep and careful assessment of the evolving treatment landscape in EoE, as well as considerations including operational challenges required for an additional clinical study, we could not justify further Eohilia development,” Takeda’s R&D chief Andy Plump, M.D., Ph.D., said during an investor call at the time. Fast forward to October 2023, when Takeda suddenly said it had refiled Eohilia in the prior month. This time, Plump said “strong data and remaining unmet need in the U.S. spurred significant grassroots support” for Eohilia from the gastrointestinal and EoE communities. Takeda worked with these communities to include additional data around Eohilia’s benefits in the resubmission, he explained. According to Plump’s comment and Eohilia’s current label, Takeda apparently played down findings from a one-year maintenance study and instead focused on the drug’s 12-week data from a phase 3 and a phase 2 trial in its resubmission. Although that strategy got Eohilia the green light from the FDA, it also led to a restriction. In Eohilia’s label, the FDA notes that the drug hasn’t shown to be effective for longer than 12 weeks. The label later points out that in a phase 3 extension study, continued treatment with Eohilia beyond 12 weeks didn’t show a statistically significant improvement versus re-randomization to placebo on some efficacy endpoints. Still, the drug appears to be a good option for 12 weeks of treatment. Between the phase 3 and phase 2 trials, Eohilia, given at 2mg twice daily, respectively helped 53% and 38% patients achieve histological remission after 12 weeks of treatment, versus 1% and 2.4% for those who received placebo. By comparison, Sanofi and Regeneron won Dupixent’s EoE nod with a 24-week analysis showing the weekly antibody drug led to histological remissions in 60% and 59% of patients in two parts of a phase 3 trial, versus 5% and 6% for the placebo group. As for disease symptoms measured by the patient-reported Dysphagia Symptom Questionnaire (DSQ), Eohilia delivered 10.2- and 14.5-point improvements, compared with 6.5- and 5.9-point improvements for placebo. Results on the same endpoint for Dupixent were 21.9 and 23.8 points, versus 9.6 and 13.9 points for placebo. Thanks to the approval, Takeda said it’s looking to reverse a previously recorded impairment loss tied to Eohilia’s rejection, but that it doesn’t expect the impact to be material. Takeda’s business has come under pressure lately after the Japanese pharma’s blockbuster ADHD drug Vyvanse lost U.S. market exclusivity in August. Adding to the woes are a phase 3 flop for the company’s stem cell therapy Alofisel in complex perianal fistulas, the global market withdrawal of EGFR lung cancer med Exkivity, and the voluntary retraction of an application for the dengue vaccine Qdenga in the U.S. The company has recently won two other FDA nods, one for colorectal cancer drug Fruzaqla, which Takeda in-licensed from Hutchmed a year ago; and the other for rare disease therapy Adzynma in congenital thrombotic thrombocytopenic purpura.

Blueprint disclosed the news alongside an update on its plans for Gavreto. Blueprint Medicines is pulling back from one of its three areas of focus, dropping two non-small cell lung cancer (NSCLC) programs in response to early clinical data on the EGFR tyrosine kinase inhibitors. One year ago, Blueprint CEO Kate Haviland used a presentation at the J.P. Morgan Healthcare Conference to explain how the company designed a phase 1 EGFR-driven lung cancer study to give “the confidence that we can win in first line.” The decision to spend 2023 gathering data to inform a go/no-go decision reflected Haviland’s recognition that lung cancer was an ambitious and potentially “expensive endeavor.” Now, Blueprint has early evidence of whether its two drug candidates, BLU-945 and BLU-451, can deliver on its aim to develop best-in-class molecules capable of replacing the standard of care in frontline, EGFR lung cancer. Haviland pulled investment in the programs after getting a look at the data.  “Combining this emerging data, from both the BLU-945 and the BLU-451 programs, with the evolving EGFR landscape, we have decided to deprioritize continued investment in EGFR-driven non-small cell lung cancer and to focus our R&D investments in the most compelling and highest value programs,” the CEO said at a JPM presentation this week. Blueprint’s interest in EGFR-driven lung cancer was built on evidence that the first three generations of TKIs had failed to address the need for a molecule that maintains activity against sensitizing mutations, notably L858R. The L858R mutation is associated with worse outcomes on the current standard of care. Blueprint believed a combination with AstraZeneca’s Tagrisso could provide more durable benefits.  While the biotech has opted against spending its own cash to pursue that belief, it will “explore strategic options, including potential out-licensing” to support further development of BLU-945 and BLU-451. Blueprint disclosed the news alongside an update on its plans for Gavreto, the approved RET inhibitor that Roche decided to drop 11 months ago. Lacking global infrastructure in lung and thyroid cancer, the approved indications for Gavreto, Blueprint is stopping global development and marketing of the drug outside of the U.S. and China. CStone Pharmaceuticals owns the rights to Gavreto in China. In the U.S., Blueprint has found “a potential alternate partner” and “is continuing to work with the involved parties to define a scenario that enables continued availability of Gavreto.” Winding down work on Gavreto outside of those markets will reduce operating expenses without affecting the $175 million Blueprint received from Royalty Pharma in 2022.