4DMT Presents Positive Interim Data from Randomized Phase II PRISM Clinical Trial of Intravitreal 4D-150 Demonstrating Favorable Tolerability & Clinical Activity in Wet AMD

4D Molecular Therapeutics, a prominent company in the field of genetic medicines with a focus on harnessing the full potential of genetic treatments for widespread diseases, has recently disclosed encouraging interim findings from the Phase II PRISM clinical trial. This trial assesses the efficacy of intravitreal 4D-150 in patients with severe disease activity and a substantial treatment burden who suffer from wet age-related macular degeneration (wet AMD). Dr. Arshad M. Khanani, M.D., M.A., FASRS, presented the data at the Angiogenesis, Exudation, and Degeneration 2024 Conference, revealing significant 24-week outcomes from the randomized Phase II Dose Expansion cohort of the PRISM clinical trial.

“We are excited to announce positive interim findings today, providing strong validation for the potential of 4D-150 as an intravitreal therapeutic for patients with wet AMD. These results suggest that 4D-150 could be a safe, convenient, and durable treatment, aiming to preserve vision in the long term,” said Dr. David Kirn, Co-founder and CEO of 4DMT. “We believe that 4D-150 has the capacity to revolutionize the current approach to treating these patients, and these findings underscore the effectiveness of our intravitreal R100 vector developed at 4DMT. I extend my gratitude to the patients and investigators participating in the PRISM trial for their contribution to reaching this significant milestone.”

Data for the phase II PRISM trial is derived from a group of 51 patients diagnosed with wet or neovascular AMD, a variant of the disease characterized by the growth of abnormal blood vessels in the rear of the eye. These individuals exhibited severe disease and a substantial treatment load, receiving an average of 10 Eylea (aflibercept) injections, a widely-used VEGF inhibitor marketed by Bayer and Regeneron, within the past 12 months. The study involves testing two single doses of 4D-150, a gene therapy. This therapy, designed to express both aflibercept and an RNA interference (RNAi) inhibitor of VEGF in the eye, is compared to the standard treatment, Eylea. Notably, the high dose of the gene therapy resulted in an 89% reduction in the number of Eylea doses needed in the 12 months following administration.

Wet AMD stands as the primary contributor to vision impairment among the elderly, impacting approximately three million individuals in the United States and Europe. DelveInsight’s analysis reveals that the overall diagnosed population of wet AMD in the 7MM was reported as ~4 million in 2021. Within this, the diagnosed population of wet AMD patients in the United States specifically was identified to be 1.2 million in the same year. This condition propels a retinal disease market valued at over $18 billion annually. Eylea currently holds the position of the highest-selling drug within this category, with sales nearing $10 billion in 2022. However, there is potential for biosimilar competition to emerge in the coming years.

Adaptimmune Announces FDA Acceptance of Biologics License Application for Afami-cel for the Treatment of Advanced Synovial Sarcoma with Priority Review

Adaptimmune Therapeutics plc, a firm transforming the approach to treating solid tumor cancers through cell therapy, has revealed that the Food and Drug Administration (FDA) has granted priority review status to its Biologics License Application (BLA) for afami-cel. Afami-cel is an experimental engineered T-cell therapy designed for advanced synovial sarcoma. The application is set for a Prescription Drug User Fee Act (PDUFA) target action date of August 4, 2024.

“The BLA submission’s approval by the FDA marks a significant stride toward transforming the approach to synovial sarcoma treatment. Our franchise holds substantial promise, and with the necessary resources and approval, we are well-positioned to introduce afami-cel, the inaugural engineered T-cell therapy for solid tumor cancer.” – Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer

Afami-cel represents an engineered T-cell receptor (TCR) T-cell therapy designed for the MAGE A4 cancer target, specifically formulated as a one-time treatment for advanced synovial sarcoma. The most recent FDA-approved therapy for this condition was Votrient in 2012. The submission of the Biologics License Application (BLA) for afami-cel was substantiated by clinical data from the SPEARHEAD-1 pivotal trial, where it successfully achieved its primary efficacy endpoint.

Approximately 39% of patients treated with afami-cel exhibited clinical responses, showcasing a median duration of response of around 12 months (CTOS 2022). In SPEARHEAD-1, the median overall survival (mOS) reached approximately 17 months, a notable improvement compared to the historical mOS of less than 12 months for individuals with synovial sarcoma who had undergone two or more prior lines of therapy. Remarkably, 70% of individuals with advanced synovial sarcoma who responded to afami-cel were still alive two years after treatment.

Astellas Submits Supplemental New Drug Application in Japan for PADCEV with KEYTRUDA for First-Line Treatment of Advanced Bladder Cancer

Astellas Pharma Inc. officially submitted a Supplemental New Drug Application (sNDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) on January 31. This application pertains to PADCEV (enfortumab vedotin (genetical recombination)) used in conjunction with KEYTRUDA (pembrolizumab (genetical recombination)) as a combined therapeutic approach for treating adults with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). If the application is approved, the PADCEV with KEYTRUDA combination has the potential to revolutionize the treatment landscape by offering an alternative to the current standard of care, platinum-containing chemotherapy, in the first-line treatment of la/mUC. Worldwide, around 573,000 new cases of bladder cancer and 212,000 fatalities are documented every year. In Japan, an estimated 25,000 individuals receive a bladder cancer diagnosis annually, with approximately 10,000 reported deaths in 2022.

“The commencement of the MHLW’s assessment of our request for enfortumab vedotin and pembrolizumab is a positive development, as we strive to enhance existing treatment choices for Japanese patients dealing with advanced stage urothelial cancer, where outcomes are typically unfavorable. This application marks progress toward the potential provision of a treatment that has shown enhanced survival rates and a deceleration in disease advancement when compared to platinum-containing chemotherapy, offering hope for improved outcomes.” – Ahsan Arozullah, M.D., M.P.H., Senior Vice President, Head of Oncology Development, Astellas

The submission of a supplemental New Drug Application (sNDA) for utilizing this combination as a first-line treatment is grounded in findings from the Phase III EV-302 clinical trial, also recognized as KEYNOTE-A39. This study demonstrated that the combination significantly enhanced both overall survival (OS) and progression-free survival (PFS) in patients with previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC) when compared to platinum-containing chemotherapy. The observed improvements were both statistically significant and clinically meaningful. The safety outcomes aligned with earlier reports on this combination, revealing no new safety concerns.

AnaMar Announces US and EU Orphan Drug Designation for AM1476 for Treating Systemic Sclerosis

AnaMar announced on February 5, 2024, that its lead clinical candidate, AM1476, has been granted Orphan Drug Designation (ODD) by both the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) for addressing Systemic Sclerosis (SSc).

AM1476 is an orally deliverable selective peripheral-acting antagonist of the 5-HT2B receptor, a small molecule with demonstrated efficacy in both in vitro and in vivo models of fibrosis. Its Phase I clinical studies have shown favorable safety and pharmacokinetic profiles. Offering a unique dual-action approach, AM1476 targets both skin and lung manifestations of Systemic Sclerosis.

The company has outlined plans for a Phase II study aimed at assessing treatment effects in Systemic Sclerosis-associated Interstitial Lung Disease (SSc-ILD). The proposed trial will involve 60 patients and will be conducted over a period of 12 months, utilizing a double-blinded, placebo-controlled randomized approach. Efficacy will be measured through parameters such as lung function and skin thickness. Leveraging its expertise in diagnostics, the company is concurrently developing biomarkers and gene signatures to pinpoint patients who are most likely to benefit from the treatment, thereby optimizing outcomes for individuals affected by fibrosis.

AnaMar’s Chief Executive Officer, Dr. Ulf Ljungberg, said: “We are delighted with the FDA’s and EMA’s decisions to grant orphan drug designation to AM1476 for SSc. This is a significant milestone and underscores the significant unmet need for novel medicines to prevent, heal and slow organ scarring from fibrotic diseases, which are often progressive and can have a poor prognosis. There is great potential in AM1476 as a unique dual-action approach to treat skin and lung manifestations of Systemic Sclerosis, especially as it represses both macrophage and fibroblast activity, whilst minimizing side effects and interactions with other medicines. We are now planning for Phase II clinical trials and look forward to commercializing our product with a pharma partner to bring better treatment options to patients with fibrosis.”

Systemic Sclerosis, an autoimmune condition, is marked by persistent inflammation and the formation of uncontrolled scar tissue (fibrosis) within the skin and several internal organs. Skin fibrosis stands out as a prominent feature of SSc, contributing significantly to disability. Monitoring the extent of skin fibrosis offers valuable clues about the progression of the disease. Additionally, Interstitial Lung Disease (ILD) frequently emerges as an early and prevalent complication of Systemic Sclerosis, underscoring its systemic nature and the need for comprehensive management strategies.

In the European Union, approximately 100,000 individuals contend with Systemic Sclerosis, a condition where up to 80% of affected individuals may experience the development of Interstitial Lung Disease (ILD).  ILD results in the gradual formation of scar tissue within the lungs, a process known as fibrosis, leading to escalating and persistent respiratory difficulties, organ impairment, and potentially fatal consequences. Presently, there is a notable absence of treatments capable of halting or reversing the scarring process in both skin and lung tissue, underscoring the urgent need for innovative therapeutic interventions to address this unmet medical need.

Based on DelveInsights’ analysis, the estimated count of diagnosed prevalent cases of Systemic Sclerosis across the 7MM was around 150,000 in 2022, with projections indicating a rise in the upcoming years. Within this cohort, approximately 47% of cases were reported in the United States. The EU4 and the UK collectively accounted for roughly 59,000 diagnosed prevalent cases of Systemic Sclerosis. Notably, the United Kingdom exhibited the highest prevalence, with an estimated 15,000 cases, while Germany was expected to have the lowest incidence among the EU4 and the UK nations. 

Systemic Sclerosis poses a significant burden on individuals and healthcare systems worldwide due to its chronic nature, debilitating symptoms, and lack of effective treatments. However, pharmaceutical companies like AnaMar and others are actively striving to alleviate this burden by developing innovative therapies targeting both skin and lung manifestations of the disease. The evolving Systemic Sclerosis therapeutics market is expected to witness substantial growth in the coming years, driven by advancements in research and development efforts, increased understanding of disease mechanisms, and the introduction of novel treatment modalities aimed at addressing unmet medical needs and improving patient outcomes.

Biosyngen Announces FDA Fast Track Designation for BST02 in Treatment of Liver Cancer 

On February 1st, 2024, Biosyngen unveiled a significant milestone in its product development journey with the announcement of Fast Track Designation (FTD) granted by the U.S. Food and Drug Administration (FDA) for its pioneering product, BST02. This groundbreaking treatment holds promise in combating various forms of liver cancer, encompassing hepatocellular carcinoma and cholangiocarcinoma. This recognition by the FDA highlights the potential of BST02 to address critical medical needs and signifies a leap forward in the fight against these devastating diseases.

BST02 achieved a significant milestone when it received approval from the FDA for Phase I/II clinical trials in October 2023. Following this accomplishment, it was also greenlit by the Center for Drug Evaluation (CDE) of the China National Drug Administration in January 2024. This dual approval signifies a remarkable feat, positioning BST02 as the first TIL cell therapy drug for liver cancer to advance to the clinical stage on a global scale. Additionally, Biosyngen’s product portfolio expanded further with BRG01, which garnered fast-track designation in July 2023. These developments underscore Biosyngen’s commitment to pioneering innovative treatments and addressing critical medical needs in oncology.

BST02 represents a groundbreaking advancement in adoptive immune cell therapy technology, specifically centered around the expansion of the patient’s own tumor-infiltrating lymphocytes (TILs). Positioned within this category, BST02 holds immense potential for revolutionizing the treatment landscape for all types of liver cancer, presenting a ray of hope for patients battling these challenging conditions. Setting itself apart from traditional TIL therapies, BST02 offers a host of advantages. Its cryopreserved form enables it to surmount distance constraints, facilitating wider accessibility and distribution. Additionally, BST02 boasts the advantage of requiring reduced doses of interleukin-2, thereby mitigating associated risks and enhancing patient safety. This innovative approach underscores the transformative impact BST02 could have on the management and outcomes of liver cancer patients worldwide.

Acepodia Announces FDA Clearance of Investigational New Drug Application for ACE2016

Acepodia made a significant announcement on February 4, 2024, revealing that the U.S. Food and Drug Administration (FDA) has granted clearance for the company’s Investigational New Drug (IND) application regarding ACE2016. ACE2016 stands as an allogeneic gamma delta 2 (γδ2) T cell therapy, specifically designed for targeting epidermal growth factor receptor (EGFR)-expressing malignancies found in patients grappling with solid tumors. This clearance marks a crucial milestone in Acepodia’s journey towards providing innovative therapeutic solutions for individuals facing challenging medical conditions. With the FDA’s approval, Acepodia is poised to advance the development and potential availability of ACE2016, potentially offering new hope and improved treatment options for patients battling EGFR-expressing malignancies.

With this regulatory clearance in hand, Acepodia is now empowered to commence a Phase 1 clinical trial, marking a pivotal moment as it embarks on the journey of evaluating ACE2016’s safety, tolerability, and pharmacodynamics in adults facing locally advanced or metastatic EGFR-expressing solid tumors. The initiation of this trial signifies a crucial step forward in Acepodia’s commitment to advancing medical research and addressing unmet needs in oncology. 

ACE2016 has demonstrated encouraging cytotoxic effects against various EGFR-expressing cancers across diverse pre-clinical study models. Anticipating the trial’s launch in the imminent months, Acepodia aims to administer treatment to the inaugural patient by the latter half of 2024. This milestone underscores the company’s dedication to expeditiously translating innovative therapies from development to patient care, offering potential breakthroughs in the treatment landscape for individuals confronting challenging malignancies.

“This milestone is a key step as we advance our pipeline of next-generation cell therapies and explore the potential of our novel Antibody-Cell Conjugation (ACC) technology in solid tumors, which remain to be unmet medical needs in the cell therapy field,” said Sonny Hsiao, Ph.D., chief executive officer of Acepodia. “The rapid progression of obtaining the third IND approval within 18 months highlights the team’s remarkable efficiency and dedication to advancing innovative programs swiftly. With our third program in the clinic, we are proud to continue progressing the field of cell therapy with the goal of delivering powerful, accessible treatments for patients through a first-of-its-kind approach.”

As per DelveInsight, the EGFR-expressing solid tumors market is poised for a significant evolution in the upcoming years, driven by advancements in targeted therapies and immunotherapies. With ongoing research uncovering new treatment modalities and biomarkers, personalized medicine approaches are expected to play a pivotal role in optimizing patient outcomes. Pharma giants such as Acepodia and others are set to lead the EGFR-expressing solid tumors market with its potential therapeutic candidate.