Astellas & AviadoBio’s Exclusive Deal for AVB-101; GSK’s Depemokimab Shows Positive Results for Nasal Polyps; Lilly’s Mirikizumab Outperforms Ustekinumab in Crohn’s Study; TREMFYA Delivers Strong Results in Crohn’s & Colitis; ENHERTU Approved in China for HER2-Mutant NSCLC.

Astellas & AviadoBio Sign Exclusive Deal for Gene Therapy AVB-101 in Frontotemporal Dementia

AviadoBio Ltd. and Astellas Pharma Inc. have announced a strategic partnership under an exclusive option and license agreement for AVB-101, an investigational AAV-based gene therapy currently in Phase I/II development for patients with frontotemporal dementia caused by progranulin mutations (FTD-GRN). Frontotemporal dementia is a rare, aggressive form of early-onset dementia that typically leads to death within three to 13 years after diagnosis. It often results in a rapid decline in cognitive and executive functions, behavioral changes, language loss, apathy, and mobility challenges. Despite its prevalence in people under 65, frontotemporal dementia is frequently underrecognized and misdiagnosed.

Through the agreement, Astellas gains an option for a worldwide exclusive license to develop and commercialize AVB-101 for FTD-GRN and other potential indications. Astellas will invest $20 million in equity and make upfront payments of up to $30 million. If Astellas chooses to exercise the option, AviadoBio could receive up to $2.18 billion in license fees and milestone payments, plus additional royalties.

“We are thrilled about the potential of this collaboration,” said Lisa Deschamps, CEO of AviadoBio. “As we complete dosing of the first cohort of patients in our Phase I/II ASPIRE-FTD trial of AVB-101, this partnership combines our gene therapy expertise with Astellas’ global capabilities. Together, we aim to deliver this much-needed therapy to families around the world who are grappling with the severe impact of FTD-GRN and other neurological diseases.”

Adam Pearson, Chief Strategy Officer of Astellas, added, “We are excited to work with AviadoBio to expand our gene therapy pipeline. AVB-101 represents a novel approach to treating FTD-GRN and aligns with our focus on genetic regulation as a key strategy. This agreement underscores our commitment to providing innovative solutions for patients living with devastating neurodegenerative diseases.”

GSK’s Depemokimab Shows Positive Phase III Results for Chronic Rhinosinusitis with Nasal Polyps

GSK plc has announced positive results from the phase III ANCHOR-1 and ANCHOR-2 trials, evaluating the efficacy and safety of depemokimab in adults with chronic rhinosinusitis with nasal polyps (CRSwNP). Both trials met their co-primary endpoints, showing a significant reduction in total nasal polyp score and nasal obstruction after 52 weeks of treatment. The incidence of treatment-emergent adverse events was comparable between depemokimab and placebo groups, with full results expected to be presented at an upcoming scientific congress.

Kaivan Khavandi, SVP of Global Respiratory/Immunology R&D at GSK, highlighted the significance of the findings: “Millions suffer from uncontrolled CRSwNP, often facing high corticosteroid use and recurrent nasal polyps post-surgery. The ANCHOR studies show depemokimab’s potential to provide targeted and sustained suppression of inflammation, offering a new therapeutic option for these patients.”

Depemokimab, the first ultra-long-acting biologic of its kind, targets interleukin-5 (IL-5), a key protein in type 2 inflammation. With an extended half-life, depemokimab has the potential to be administered once every six months, offering long-lasting relief for CRSwNP patients, while reducing the need for frequent clinic visits.

The results from ANCHOR-1 and ANCHOR-2, combined with data from the SWIFT trials in severe asthma, will be used for global regulatory filings. If approved, depemokimab could significantly advance the treatment landscape for CRSwNP, benefiting patients who currently face inadequate or suboptimal treatment options.

Lilly’s Mirikizumab Outperforms Ustekinumab in One-Year Phase III Crohn’s Study

Eli Lilly and Company has announced encouraging results from the VIVID-1 Phase III trial, which evaluated mirikizumab in patients with moderately to severely active Crohn’s disease. Data revealed that more patients treated with mirikizumab achieved a histologic response at Week 52 compared to those treated with ustekinumab, regardless of prior biologic experience. This study marks the first Phase III trial for any approved or investigational treatment in Crohn’s disease to evaluate histologic and endoscopic outcomes systematically across five bowel segments, as presented at the United European Gastroenterology (UEG) Week in Vienna, Austria.

Mirikizumab, an IL23p19 antagonist, selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. This mechanism targets the underlying inflammation driving Crohn’s disease, a chronic inflammatory bowel disease that can cause progressive damage to the intestines and impair a patient’s quality of life. “These histologic data build on the growing evidence for mirikizumab, which may provide a greater depth of mucosal healing for those living with this chronic, progressive disease,” said Fernando Magro, M.D., head of clinical pharmacology at University Hospital São João.

Results from the trial showed that 58.2% of patients treated with mirikizumab achieved a histologic response by Week 52, compared to 48.8% for ustekinumab. In patients with previous biologic failure, the response rate was similarly higher for mirikizumab (56.5% vs. 41.3%). Notably, the study also assessed endoscopic-histologic response, showing mirikizumab’s potential to address deep tissue healing. The safety profile of mirikizumab was consistent with previous studies in ulcerative colitis, with common adverse events including COVID-19, anemia, and upper respiratory infections.

Mark Genovese, M.D., Senior VP of Lilly Immunology Development, highlighted the importance of this breakthrough: “By aligning histologic outcomes with ECCO’s recent position statement, we’re setting a new standard in the evaluation of Crohn’s disease treatments.” Lilly has submitted global regulatory applications for mirikizumab and continues its research into the drug’s long-term safety and efficacy, including studies in pediatric patients and further trials in ulcerative colitis, marketed under the name OMVOH.

Johnson & Johnson has shared promising results from their ongoing clinical trials on TREMFYA (guselkumab) for the treatment of Crohn’s disease and ulcerative colitis. Data presented at the United European Gastroenterology (UEG) Week 2024 show that TREMFYA® demonstrated high rates of endoscopic remission in both biologic-naïve and biologic-refractory patients, including those who had not responded to JAK inhibitors. These findings, drawn from the Phase III GALAXI 2 & 3 studies in CD and the QUASAR maintenance study in ulcerative colitis, are crucial as they indicate significant potential for TREMFYA to be a differentiated treatment option, especially for patients who have previously failed biologic therapies.

In biologic-naïve patients with Crohn’s Disease, TREMFYA showed superior endoscopic remission rates compared to ustekinumab in the pooled Phase III GALAXI 2 & 3 dataset. At Week 48, 44% of patients receiving TREMFYA 100 mg every eight weeks (q8w) achieved endoscopic remission, while the 200 mg every four weeks (q4w) dose saw a slightly higher rate of 46.1%. This is compared to ustekinumab, which showed a 29.8% remission rate in the same population. In the QUASAR study, similar improvements were seen in biologic/JAK inhibitor-naïve patients with ulcerative colitis, where endoscopic remission was achieved in 38.1% of patients on the 100 mg q8w dose, and 41.7% on the 200 mg q4w dose, compared to 20.4% in the placebo group.

The studies also assessed the impact of TREMFYA® on biologic-refractory patients with Crohn’s Disease and JAK inhibitor-refractory patients with ulcerative colitis. In the biologic-refractory Crohn’s Disease group, 28.1% of patients treated with TREMFYA 100 mg q8w and 28.6% with the 200 mg q4w dose achieved endoscopic remission, compared to 20.5% with ustekinumab. For ulcerative colitis patients refractory to biologics or JAK inhibitors, the QUASAR study showed endoscopic remission rates of 31.2% in those on 100 mg q8w and 23.9% in those on 200 mg q4w, compared to just 8% in the placebo group, marking a significant improvement in this difficult-to-treat population.

The U.S. FDA recently approved TREMFYA® in September 2024 for treating adults with moderately to severely active ulcerative colitis, and its application for Crohn’s Disease is currently under review. Regulatory submissions are also underway in Europe for both indications. These results not only reinforce the well-established safety profile of TREMFYA but also solidify its role as a key player in treating inflammatory bowel diseases.

ENHERTU Approved in China as First HER2-Targeted Treatment for HER2-Mutant NSCLC

AstraZeneca and Daiichi Sankyo have achieved a significant milestone with ENHERTU (trastuzumab deruxtecan) receiving conditional approval in China for the treatment of HER2-mutant non-small cell lung cancer (NSCLC). This approval marks an important breakthrough for patients with unresectable, locally advanced, or metastatic NSCLC who have received prior systemic therapy. The approval by China’s National Medical Products Administration (NMPA) is based on positive results from the DESTINY-Lung02 and DESTINY-Lung05 Phase II trials, and full approval will depend on further confirmatory trial results that demonstrate clinical benefit.

Lung cancer is a significant public health concern in China, with over a million new cases diagnosed annually, accounting for more than 40% of the global lung cancer population. Among these, 2% to 4% of NSCLC patients have HER2 mutations, which historically had limited treatment options. According to Ying Cheng, MD, PhD, Director of Jilin Lung Cancer Centre, the approval of ENHERTU is a critical step forward, as it provides a much-needed targeted therapy for patients with this aggressive subtype of lung cancer. Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Business Unit, emphasized that this is the first HER2-directed therapy approved in China for HER2-mutant NSCLC, highlighting the importance of biomarker testing in treatment personalization.

The clinical data backing this approval comes from the DESTINY-Lung02 trial, where ENHERTU showed a confirmed objective response rate (ORR) of 49% in patients from Japan, Korea, and Taiwan, with a median duration of response (DoR) of 16.8 months and a progression-free survival (PFS) of 9.9 months. Meanwhile, the DESTINY-Lung05 trial in China revealed an even higher ORR of 58.3% in previously treated patients, showcasing ENHERTU’s consistent efficacy across different populations. These results are promising, providing hope for improved outcomes in patients with HER2-mutant NSCLC.

ENHERTU is a HER2-directed antibody-drug conjugate (ADC) jointly developed by AstraZeneca and Daiichi Sankyo, and its approval in China for NSCLC follows its previous success in HER2-positive breast and gastric cancers. The drug is now approved in more than 45 countries, including the US, Japan, and across the EU. This fourth approval in China demonstrates the broad potential of ENHERTU across multiple tumor types, solidifying its place in oncology as a versatile and highly effective treatment for HER2-targetable cancers.