AskBio Announces First Patient Randomized in Phase 1 Trial of AB-1005 Gene Therapy for Multiple System Atrophy-Parkinsonian Type

Asklepios BioPharmaceutical, Inc., a gene therapy firm fully owned and independently operated under Bayer AG, announced the initiation of the Phase I REGENERATE MSA-101 clinical trial for AB-1005 at the Ohio State University Wexner Medical Center. The first patient has been randomized in this trial, representing a noteworthy advancement in the development of AB-1005 gene therapy. AB-1005, an adeno-associated viral vector encoding glial cell line-derived neurotrophic factor (AAV2-GDNF), is targeted for the treatment of multiple system atrophy-parkinsonian type (MSA-P), bringing it one step closer to potential patient application. Additionally, AB-1005 is under investigation for mild to moderate Parkinson’s disease, with the Phase Ib study now having completed its enrollment process.

“It holds great significance for the MSA community to learn that the initial participant has been registered in the Phase 1 REGENERATE MSA-101 trial,” expressed Philip M. Fortier, MA, President and Executive Director of the Defeat MSA Alliance. “MSA lacks a cure, and there are presently no therapies available to halt or decelerate the disease’s progression. This adds an extra layer of difficulty for patients, considering the swift deterioration that many will undergo. Achieving this milestone today raises optimism about potentially altering the course for individuals affected by MSA.”

MSA-P, often challenging to differentiate from Parkinson’s disease in its initial stages, manifests through symptoms such as slowed movements, coordination issues, imbalance, and dizziness, leading to progressively impaired mobility. This deterioration stems from the gradual decline of nerve cells in both the brain and spinal cord. Considered a rare condition affecting an estimated 100,000–500,000 individuals globally, MSA generally emerges unexpectedly and typically starts to show symptoms in individuals in their 50s, rapidly progressing within a span of 5–10 years.

Almirall Receives European Commission Approval of EBGLYSS for Moderate-to-Severe Atopic Dermatitis

Almirall S.A., a leading global biopharmaceutical firm specializing in medical dermatology, revealed that the European Commission (EC) has granted approval for EBGLYSS (lebrikizumab) in the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients aged 12 years and older with a body weight of at least 40 kg, who are suitable candidates for systemic therapy. The initial commercial launch of EBGLYSS will take place in Germany, with plans to progressively introduce it to additional European countries throughout the year 2024.

Lebrikizumab, a monoclonal antibody, exhibits high-affinity binding to IL-13, preventing the formation of the IL-13Rα1/IL-4Rα heterodimer complex. This targeted action inhibits the biological effects of IL-13, a pivotal cytokine in atopic dermatitis. IL-13 drives the type-2 inflammatory loop, contributing to skin barrier dysfunction, itch, skin thickening, and infection. With proven short and long-term efficacy and safety demonstrated over 2 years, Lebrikizumab represents a significant advancement for patients with moderate-to-severe AD unresponsive to topical therapy. The monthly maintenance dosing further enhances its appeal for all patients.

“The approval granted by the EC for lebrikizumab offers a vital treatment avenue for individuals grappling with moderate-to-severe AD. With its proven efficacy in both short and long-term use, along with monthly maintenance dosing and a consistent safety profile, this treatment holds promise as a primary biologic option. This regulatory achievement underscores Almirall’s unwavering dedication to pioneering innovative therapies that significantly impact the lives of those battling skin diseases,” commented Dr. Volker Koscielny, Chief Medical Officer at Almirall.

The approval stems from three pivotal Phase III trials, namely ADvocate 1, ADvocate 2, and ADhere, which investigated lebrikizumab both as a standalone therapy and in combination with topical corticosteroids (TCS). These studies involved adult and adolescent patients grappling with moderate-to-severe atopic dermatitis. Lebrikizumab exhibited early clinical efficacy in monotherapy, achieving a reduction of at least 75% in disease extent and severity (EASI-75) in nearly 6 out of 10 patients by week 16. In combination with topical corticosteroids, this milestone was reached in almost 7 out of 10 patients. Among Week 16 responders who continued lebrikizumab treatment—either as monotherapy or in combination with TCS—for up to two years, close to 80% experienced sustained skin clearance, relief from itchiness, and a decrease in disease severity, thanks to monthly maintenance dosing.

Bayer Stopped OCEANIC-AF Study Early Due to Lack of Efficacy

The OCEANIC-AF trial, a phase III investigation comparing asundexian to apixaban for patients with atrial fibrillation at stroke risk, is being halted prematurely. This decision comes from the Independent Data Monitoring Committee (IDMC), which, through continuous monitoring, observed lower effectiveness of asundexian compared to the control (apixaban).

The safety data available align with previously reported profiles of asundexian. The IDMC suggests proceeding with the OCEANIC-STROKE phase III study according to the original plan.

Necessary steps will be taken to conclude the OCEANIC-AF study, and patients will receive communication from their healthcare providers/researchers regarding future actions.

Dr. Christian Rommel, a member of Bayer AG’s Pharmaceutical Division Executive Committee and Global Head of Research and Development, mentioned, “Although these findings do not support continuing the OCEANIC-AF study, we will persist in exploring asundexian in the OCEANIC-STROKE study and reconsider its use in other conditions requiring antithrombotic treatment.”

Further evidence indicates the potential benefits of anticoagulation therapy beyond standard care in the patient population studied in OCEANIC-STROKE, where treatment options are limited.

Asundexian remains an investigational drug and has not received approval from any health authority for use in any country or for any specific purpose.

Pfizer and Astellas’ XTANDI Approved by FDA in Earlier Prostate Cancer Treatment Setting

Astellas Pharma Inc. and Pfizer Inc. announced the U.S. Food and Drug Administration’s (FDA) approval of a supplemental New Drug Application for XTANDI® (enzalutamide) after expedited development and review programs by the FDA (including Priority Review designation, Fast Track designation, and Real-time Oncology Review). This approval, based on findings from the Phase 3 EMBARK trial, establishes XTANDI as the first and sole androgen receptor signaling inhibitor sanctioned by the FDA for treating patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC) experiencing biochemical recurrence at high risk of metastasis (high-risk BCR). Patients falling under this category may opt for XTANDI treatment with or without a gonadotropin-releasing hormone (GnRH) analog therapy.

It’s estimated that between 20-40% of men who’ve undergone definitive prostate cancer treatments, such as radical prostatectomy, radiotherapy, or both, will encounter biochemical recurrence (BCR) within 10 years. Around nine out of 10 men with high-risk BCR will eventually develop metastatic disease, leading to one in three deaths due to metastatic prostate cancer.

The approval is based on outcomes from the Phase 3 EMBARK trial, which investigated XTANDI combined with leuprolide, placebo with leuprolide, and XTANDI alone (as a single agent) in patients with nonmetastatic hormone-sensitive prostate cancer (nmHSPC or nmCSPC) with high-risk BCR.

XTANDI is presently under evaluation by other regulatory authorities worldwide, including the European Medicines Agency, to broaden its indication in nmHSPC (or nmCSPC) with high-risk BCR based on the EMBARK trial results.

FDA Grants Orphan Drug Designation to EPI-321, Epic Bio’s Novel Genetic Medicine Candidate 

Epic Bio announced on November 16, 2023, that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to its therapy EPI-321 for the treatment of Facioscapulohumeral Muscular Dystrophy (FSHD), the most prevalent form of muscular dystrophy among adults. 

EPI-321 is an investigational epigenetic treatment that targets the fundamental molecular processes of FSHD by reinstating methylation within the D4Z4 region of chromosome 4, thereby interrupting the harmful expression of the DUX4 gene. Administered through a single AAV vector (AAVrh74), clinically endorsed for muscle delivery, EPI-321 effectively reaches muscle tissue. Preclinical investigations of EPI-321 have exhibited its strong capacity to significantly inhibit the abnormal expression of the DUX4 gene and diminish the death of muscle cells.

“We are pleased the FDA has recognized the unmet need of those living with FSHD by granting this Orphan Drug Designation, and we believe EPI-321 could serve as an important new therapeutic option for these patients,” said Weston Miller, M.D., chief medical officer of Epic Bio. “We are working diligently to advance EPI-321 toward the clinic, and we look forward to generating meaningful clinical data to inform its future development as a potential new treatment for FSHD.”

Epic intends to commence a Phase 1/2 clinical trial, marking the first human study of EPI-321, slated to begin in the initial half of 2024. This multi-center trial aims to evaluate the safety, effectiveness, and initial potential of EPI-321 in individuals diagnosed with Facioscapulohumeral Muscular Dystrophy.

According to the FSHD Society (2020), FSHD is one of the most common muscular dystrophies, with a prevalence of 1 in 8,333 to 1 in 10,000 individuals in the US. As per DelveInsight, in 2022, the total prevalent cases of Facioscapulohumeral Muscular Dystrophy were 79,000 in the 7MM, which is expected to increase in the upcoming years. In 2022, among the 7MM, the United States accounted for the highest number of total prevalent cases of FSHD i.e. ~34,000 which is expected to increase by the year 2032. Both males and females can be affected by FSHD, with symptoms appearing in 90 percent of patients before reaching 20 years of age. The condition varies in intensity, showcasing progressive muscle weakening and tissue shrinkage in the facial, shoulder, upper arm, and lower leg regions. By the time they reach 50, around 25 percent of individuals with Facioscapulohumeral Muscular Dystrophy may require a wheelchair for mobility. 

Presently, there aren’t any treatments altering the course of FSHD; instead, supportive care serves as the cornerstone of its management. This care predominantly revolves around physical therapy and rehabilitation exercises. Effectively addressing pain and fatigue in FSHD patients is crucial, as both symptoms can significantly impact the psychological well-being of the patient. Growing numbers of companies and academic laboratories are pressing forward with early-stage drug development efforts. To overcome the existing treatment challenges, several major pharma and biotech companies like Epic Bio, among others, are actively working in the therapeutics market.

Chemomab Therapeutics Receives FDA Fast Track Designation for CM-101 for the Treatment of Primary Sclerosing Cholangitis (PSC)

Chemomab Therapeutics Ltd. (Nasdaq: CMMB) (Chemomab) announced on November 15, 2023, that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to its therapy, CM-101, for the treatment of Primary Sclerosing Cholangitis (PSC) in adult patients. PSC is a liver disease characterized by fibrosis and can lead to complications like liver transplant, cancer, and premature mortality.

CM-101 is a pioneering monoclonal antibody, that targets the soluble protein CCL24, associated with crucial pathways in PSC’s physiological processes, as evidenced in both preclinical and clinical research. Its dual functionality of anti-inflammatory and anti-fibrotic actions aims to disrupt the destructive cycle fueling these pathways, showing promise in modifying the disease course based on preclinical and initial clinical studies focusing on PSC-related mechanisms.

“This FDA Fast Track designation is an important validation of CM-101’s potential to have a major impact on this devastating disease that attacks people in their prime years and lacks any approved treatments,” said Adi Mor, Ph.D., co-founder, Chief Executive Officer and Chief Scientific Officer of Chemomab. “We designed the CM-101 Phase 2 SPRING trial to be supportive of a registrational trial in patients with PSC, and we welcome the enhanced opportunities for working closely with the FDA and for the acceleration of the development and review process provided by Fast Track status.”

Chemomab Chief Medical Officer Matt Frankel, MD, added, “Promising biomarker and elastography results from our Phase 2a liver fibrosis study in nonalcoholic steatohepatitis (NASH) patients reported earlier this year reinforced our optimism about the therapeutic potential of CM-101. There are common fibrosis pathways in NASH and PSC, and CM-101’s relevance to PSC is supported by extensive preclinical and patient sample studies. We also are encouraged by robust patient enrollment in the SPRING trial, which speaks to the high unmet need experienced by these patients. We look forward to continuing our work with PSC patients, their clinicians and the FDA to expedite advancement of CM-101 as a potential treatment for this terrible disease.”

In a Phase 1b investigation, it exhibited enhancements in liver biomarkers, reduced liver stiffness, and displayed a favorable PK (pharmacokinetics) and target engagement profile among individuals with nonalcoholic fatty liver disease (NAFLD). Findings from a Phase 2a trial on liver fibrosis in NASH patients (NCT05824156), reported earlier this year, showcased consistent and positive advancements in crucial inflammatory and fibrogenesis-related biomarkers. Some of these improvements suggest a potential transition to efficacy in addressing PSC. CM-101 holds Orphan Drug designations from both the FDA and Europe’s EMA and is presently under assessment in Primary Sclerosing Cholangitis patients in the Phase 2 SPRING trial. Patient recruitment for the trial is nearing conclusion, and Chemomab expects to provide initial findings by the latter half of 2024.

Primary Sclerosing Cholangitis is an uncommon liver disease, that progresses with inflammation and the formation of scar tissue (fibrosis) in the bile ducts, potentially leading to liver cirrhosis and failure. Additionally, PSC heightens the likelihood of various cancers, accounting for approximately half of PSC-related deaths. While PSC can develop in individuals of any age, gender, or racial background, it’s more prevalent in men and is commonly diagnosed in patients around their 40s. The exact cause of PSC remains unknown, although about 75% of those with PSC also have inflammatory bowel disease.
Currently, there are no approved treatments for Primary Sclerosing Cholangitis by the FDA or EMA. Liver transplants are frequent in severe cases, yet even after transplantation, PSC reemerges in approximately 20% of recipients. There exists a significant gap in available treatments, highlighting a pressing need for therapeutic options that can manage symptoms and alter the course of this debilitating condition.