Takeda and AC Immune Ink Exclusive Deal for Active Immunotherapy in Alzheimer’s, Focusing on Amyloid Beta

Takeda and AC Immune SA have unveiled an exclusive global option and licensing pact concerning AC Immune’s active immunotherapies directed at harmful variants of amyloid beta (Abeta), notably ACI-24.060, intended for Alzheimer’s disease treatment.

ACI-24.060 is a candidate for active immunotherapy against Abeta, aimed at stimulating a strong antibody response to counter the harmful forms of Abeta, which are implicated in the formation of plaques and the advancement of Alzheimer’s disease. By promoting the clearance of plaques and effectively preventing their formation in the brain, ACI-24.060 holds promise in potentially slowing down the progression of Alzheimer’s disease. Currently, ACI-24.060 is undergoing investigation in the ABATE trial, which is a randomized, double-blind, placebo-controlled Phase Ib/II study. This trial aims to evaluate the safety, tolerability, immunogenicity, and pharmacodynamic effects of this experimental immunotherapy in individuals with prodromal Alzheimer’s disease and in adults with Down syndrome.

“We, as pioneers in active immunotherapy, are pioneering an innovative approach that could revolutionize Alzheimer’s treatment and alleviate the complex challenges faced by patients and the wider community. We believe that partnering with Takeda at this crucial stage in ACI-24.060’s development will maximize its impact, enabling us to swiftly advance into Phase III trials. Dr. Andrea Pfeifer, CEO of AC Immune, stated, ‘This collaboration allows us to harness Takeda’s expertise, strategic vision, and financial capabilities, essential for conducting comprehensive global Phase III trials in Alzheimer’s disease. It also enables us to concentrate on completing Phase Ib/II development and accelerating our efforts to replicate this success with increased funding for our early-stage pipeline.”

AC Immune will take charge of finishing the ABATE trial. Upon exercising the option, Takeda will handle and finance all subsequent clinical development, oversee all global regulatory tasks, and manage worldwide commercialization.

According to the agreement, AC Immune will get an initial payment of $100 million. Additionally, they can receive more payments, totaling up to about $2.1 billion, based on certain milestones achieved during the agreement. After the product is commercialized, AC Immune will also earn royalties on global sales, with the exact amount depending on sales tiers.

Eli Lilly’s Donanemab Under FDA Review for Early Alzheimer’s Treatment

The FDA is set to host a face-to-face gathering of the Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) on June 10, 2024, focusing on donanemab, a submission by Eli Lilly and Company aimed at treating early symptomatic Alzheimer’s disease. While the open public hearing segment of the meeting will take place online.

The Phase III trial, known as TRAILBLAZER-ALZ 2, included in this application, is a study designed to assess the safety and effectiveness of donanemab. It follows a double-blind, placebo-controlled format and targets individuals aged 60-85 with early symptomatic Alzheimer’s disease (either mild cognitive impairment or mild dementia caused by Alzheimer’s disease), who have confirmed Alzheimer’s neuropathology. Alzheimer’s is a progressive and ultimately fatal illness, affecting 6-7.5 million Americans during its early symptomatic phases. The trial recruited 1,736 participants from eight countries, selected based on cognitive evaluations alongside imaging for amyloid plaque and tau staging using positron emission tomography (PET).

The findings from the TRAILBLAZER-ALZ 2 investigation were released in the Journal of the American Medical Association (JAMA). Lilly is persistently examining donanemab across various clinical trials, such as TRAILBLAZER-ALZ-3, which investigates its potential for Alzheimer’s disease prevention.

Bristol Myers Squibb Releases Latest Findings from Phase III CheckMate -73L Trial

Bristol Myers Squibb reported that the Phase III CheckMate -73L trial did not achieve its primary goal of improving progression-free survival (PFS) in patients with unresectable, locally advanced stage III non-small cell lung cancer (NSCLC). The trial compared the effectiveness of Opdivo® (nivolumab) in combination with concurrent chemoradiotherapy (CCRT) followed by Opdivo plus Yervoy® (ipilimumab) against CCRT followed by durvalumab. Adverse events observed with Opdivo in combination with CCRT followed by Opdivo plus Yervoy were generally in line with what was already known about each component’s side effect profiles.

CheckMate -73L represents a Phase III clinical study that is randomized and open-label. It aims to assess the effectiveness of Opdivo in combination with concurrent chemoradiotherapy (CCRT), followed by either Opdivo plus Yervoy or Opdivo alone, compared to CCRT alone followed by durvalumab. The trial focuses on patients with locally advanced stage III non-small cell lung cancer (NSCLC) who cannot undergo curative surgery. A total of 925 patients were randomly assigned to different treatment arms. The primary goal of the study is to evaluate progression-free survival (PFS) using RECIST 1.1 criteria by blinded independent central review (BICR) between Arm A (Opdivo with CCRT followed by Opdivo plus Yervoy) and Arm C (CCRT followed by durvalumab). Secondary objectives include overall survival (OS) among all treatment arms, PFS across all arms, objective response rate (ORR), time to response (TTR), and duration of response (DOR) using RECIST 1.1 by BICR, along with additional safety and efficacy measures.

Joseph Fiore, vice president of thoracic cancers at Bristol Myers Squibb, expressed disappointment that combining immunotherapy with definitive chemoradiation didn’t enhance progression-free survival outcomes. He emphasized the ongoing necessity to enhance long-term outcomes for these patients and indicated that these findings will guide future drug development endeavors in this area. Fiore also extended gratitude to the patients, families, and investigators for their valuable contributions to this significant research.

The company plans to thoroughly assess the data and collaborate with researchers to disseminate the findings within the scientific community. Opdivo and Opdivo-based combinations have demonstrated favorable results and are authorized therapies for suitable patients dealing with resectable or metastatic NSCLC.

FDA Grants Priority Review to Dupixent sBLA for Treating Adolescents with Chronic Rhinosinusitis with Nasal Polyposis

Regeneron Pharmaceuticals, Inc. and Sanofi announced that the FDA has agreed to prioritize the review of the supplemental Biologics License Application (sBLA) for Dupixent® (dupilumab) as a maintenance treatment addition for adolescents aged 12 to 17 years experiencing inadequately controlled chronic rhinosinusitis with nasal polyposis (CRSwNP). The FDA’s decision is expected by September 15, 2024. Dupixent is presently authorized as an add-on maintenance therapy for adults with CRSwNP whose condition is not sufficiently managed.

The approval of Dupixent for adolescents is backed by extending the effectiveness findings from two successful pivotal trials (SINUS-24 and SINUS-52) conducted in adults with CRSwNP. These trials revealed that Dupixent notably enhanced nasal congestion severity, reduced nasal polyp size, and improved sense of smell, all while decreasing the reliance on systemic corticosteroids or surgery compared to a placebo over 24 weeks. Additionally, the safety profile of Dupixent in its existing approved uses for adolescents further reinforced the support for its supplemental Biologics License Application (sBLA).

The safety outcomes observed in both the SINUS-24 and SINUS-52 trials were largely in line with the known safety profile of Dupixent in its approved uses. Adverse effects, such as injection site reactions and joint pain, were more frequently reported with Dupixent (≥3%) compared to a placebo in the combined safety analysis of the 24-week duration of these trials. Regulatory applications aiming for approval of treatments that could offer significant advancements in managing severe conditions are granted Priority Review. However, no regulatory body has thoroughly assessed the potential utilization of Dupixent in treating adolescents with CRSwNP yet.

Excision BioTherapeutics Unveils Phase I/II Trial Results of EBT-101 in HIV, Alongside Promising In Vivo Efficacy Data in Herpes Virus and Hepatitis B

Excision BioTherapeutics, Inc. presented a summary of several new studies at the recent American Society of Gene and Cell Therapy (ASGCT) meeting. Their HIV program, which employs CRISPR-based systemic treatment, marked the pioneering in vivo clinical trial of its kind in the United States. The EBT-101-001 clinical study, designed with an open-label approach, aimed primarily to evaluate safety and tolerance levels.

Daniel Dornbusch, Excision’s CEO, emphasized the paramount importance of prioritizing participant safety when evaluating any new molecular entity, especially innovative treatments like CRISPR-based therapies. The EBT-101-001 trial, being the first of its kind in humans, was meticulously crafted to primarily assess the safety and tolerance of CRISPR administered systemically. Safety and tolerance stood as the primary focus of the study, while secondary objectives included examining biodistribution and immunogenicity.

“We understand that numerous individuals were optimistic about the potential of the initial trial to demonstrate a potential HIV cure, given the field’s prolonged anticipation spanning over two decades. Nonetheless, it was crucial for this clinical trial to prioritize establishing the safety of EBT-101 as a gene therapy product, alongside safety considerations concerning the application of CRISPR within the field,” remarked Dr. William Kennedy, Senior Vice President of Clinical Affairs at Excision.

Details regarding the provided data:

  • In the EBT-101 clinical study, no severe adverse effects were reported, and only minor grade 1 adverse effects were linked to the treatment. All occurrences, even those not directly related to the therapy, were either mild (grade 1) or moderate (grade 2) in severity on a scale of 1 to 5, and they resolved without requiring any intervention.
  • In the preclinical trials of EBT-104, a solitary treatment significantly decreased Herpes Virus DNA by more than 99.99% in Vero cells, and nearly eradicated viral shedding, with only one instance out of twelve observed in the rabbit keratitis model.
  • In the preclinical trials of EBT-107, a lipid nanoparticle (LNP) administered CRISPR compound significantly decreased HBV DNA, HBsAg (s-antigen), and HBeAg (e-antigen) levels by 98%, 97%, and 92% respectively in a mouse model of HBV. Since EBT-107 is delivered via LNP, it may be re-administered to potentially reach the desired therapeutic effectiveness.