The FDA clearance is based on the 48-week findings of the PULSAR and PHOTON studies, which were two double-blind, active-controlled pivotal trials comparing EYLEA HD to EYLEA (aflibercept) Injection 2 mg. Both the PULSAR trial in wAMD (N=1,009) and PHOTON trial in DME (N=658) met their primary endpoint, with EYLEA HD demonstrating non-inferior and clinically equivalent vision gains at 48 weeks with both 12- and 16-week dosing regimens after only 3 initial monthly doses, compared to an EYLEA 8-week dosing regimen after initial monthly doses (3 in PULSAR and 5 in PHOTON). The vast majority of patients who were randomly assigned to EYLEA HD 12- or 16-week dosage regimens (after three initial monthly doses) were able to sustain these treatment intervals for 48 weeks.
EYLEA HD is being developed together by Regeneron and Bayer AG. Regeneron has exclusive rights to EYLEA and EYLEA HD in the United States. Bayer has licensed exclusive marketing rights outside of the United States, where the businesses will split revenues from EYLEA and EYLEA HD sales after regulatory approvals. Regulatory submissions for aflibercept 8 mg are being reviewed in Europe and Japan. Submissions to other regulatory authorities in other countries are also anticipated.
Veopoz Receives FDA Approval as the First Treatment for Children and Adults With CHAPLE Disease
The FDA has approved Veopoz (pozelimab-bbfg) for the treatment of adult and pediatric patients 1 year of age and older with CHAPLE disease, also known as CD55-deficient protein-losing enteropathy, according to Regeneron Pharmaceuticals, Inc. Veopoz is the first and only medicine approved for CHAPLE. The pre-approval inspection issues associated with the aflibercept 8 mg BLA have been addressed with the permission of Veopoz. The FDA is likely to take action on the aflibercept 8 mg BLA in the coming weeks.
Most patients with CHAPLE disease are children who face severely debilitating symptoms and often life-threatening complications that begin in infancy,” said Michael Lenardo, M.D., Chief, Molecular Development of the Immune System Section; Co-Director, Clinical Genomics Programme, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH). “As an investigator in this pivotal trial and one of the disease’s discoverers, I witnessed firsthand the transformational clinical improvement that pozelimab achieves in CHAPLE patients.” The approval of pozelimab is a significant achievement, as it provides a new treatment that can benefit these long-suffering patients.
CHAPLE is an extremely rare and potentially fatal genetic immunological disease caused by an overactive complement system. The complement system is a mechanism that kills microorganisms in healthy people. Those with CHAPLE, on the other hand, are unable to regulate complement activity due to CD55 gene alterations. Without correct CD55 regulation, the complement system may assault normal cells, causing damage to blood and lymph arteries in the upper digestive tract and resulting in protein loss. There are less than ten patients in the United States who have CHAPLE disease. Veopoz, a completely human monoclonal antibody, is intended to target complement factor C5, a protein involved in the activation of the complement system.
The FDA approval is based on the findings of Phase II/III open-label trial that looked at the efficacy and safety of pozelimab in 10 patients ranging in age from 3 to 19 years (median age of 8.5 years). On day one, patients received a single intravenous loading dose of pozelimab 30 mg/kg, followed by weekly weight-based subcutaneous doses of pozelimab.
FDA Places Second Partial Clinical Hold on AML Enrollment for Magrolimab Trials
The enrollment of new patients in clinical trials within the United States, focusing on the potential groundbreaking anti-CD47 immunotherapy magrolimab for acute myeloid leukemia (AML) treatment, has been partially halted again by the FDA. Gilead Sciences announced this development. The decision from the FDA comes after the discontinuation of the phase 3 ENHANCE trial (NCT04313881), which was assessing magrolimab in patients with higher-risk myelodysplastic syndromes (HR-MDS).
Effective immediately, the screening and enrollment of fresh patients under the US investigational new drug application (IND 147229) and the US Expanded Access Program will be temporarily stopped. However, patients who are already participating in AML clinical trials investigating magrolimab will be permitted to continue their treatment and follow-up procedures as per the existing study protocol.
The impacted trials encompass the phase 3 ENHANCE-2 trial (NCT04778397), comparing the magrolimab and azacitidine combination against venetoclax (Venclexta) combined with azacitidine or intensive chemotherapy in treatment-naïve patients with TP53-mutant AML. Also affected is the phase 3 ENHANCE-3 trial (NCT05079230), which is studying magrolimab along with venetoclax and azacitidine versus placebo in combination with venetoclax and azacitidine for AML treated patients unsuitable for chemotherapy.
In January 2022, the FDA initially placed a partial clinical hold on all trials evaluating magrolimab in combination with azacytidine. However, in April 2022, following a comprehensive safety data review, the FDA lifted the clinical hold for trials involving the combination therapy for patients with MDS and AML.
Globally, regulatory agencies and clinical trial investigators involved in these studies have been informed about the FDA’s decision. Importantly, trials exploring magrolimab’s use in solid tumors such as head and neck cancer, colorectal cancer, lung cancer, and breast cancer will remain unaffected by this FDA action.
Gilead is collaborating with regulatory agencies to outline the subsequent steps for resolving the partial clinical hold and recommencing new patient enrollment in AML-focused magrolimab studies.
Incannex Healthcare Receives US FDA Approval For Sleep Apnoea Clinical Trial
Incannex Healthcare Ltd has gained approval from the US Food and Drug Administration (FDA) to initiate a Phase 2/3 clinical trial for its IHL-42X asset, developed to tackle obstructive sleep apnea. This clinical-stage pharmaceutical company, which specializes in creating proprietary medicinal cannabinoid products and psychedelic-assisted psychotherapies to address unmet medical needs, secured this endorsement after submitting an Investigational New Drug (IND) application to the FDA the previous month.
The FDA, following an evaluation of the trial protocol, lead investigators, and a risk-benefit analysis of both the trial and the potential product, has sanctioned the clinical trial to proceed due to its deemed safety. With this significant achievement under its belt, Incannex will move forward with the completion of institutional review board applications and submissions for the primary clinical trial sites.
The trial, spanning multiple centers, will explore the efficacy of IHL-42X as a treatment for OSA in patients who are either non-compliant, intolerant, or new to positive airway pressure treatments such as continuous positive airway pressure (CPAP) devices. Over the 52-week treatment period, participants will be administered a single dose of IHL-42X, dronabinol, acetazolamide, or a placebo.
Throughout the trial duration, participants will engage in daily sleep quality surveys and attend monthly clinic appointments to evaluate functional sleep outcomes, cognitive performance, and other safety and efficacy indicators. Polysomnography assessments will be conducted every three months to analyze the impact of treatment on parameters like the Apnoea Hypopnea Index (AHI) and other sleep-related metrics. The efficacy of all drug treatments will be compared against the effects of the placebo.
Avidity Receives FDA Orphan Drug Designation for AOC 1044 for Treatment of Duchenne Muscular Dystrophy
Avidity Biosciences, Inc. (Nasdaq: RNA) announced on August 15, 2023, that the U.S. Food and Drug Administration (FDA) has officially designated AOC 1044, the company’s investigational treatment for Duchenne Muscular Dystrophy (DMD) in individuals with mutations suitable for exon 44 skipping (DMD44), as an Orphan Drug. Duchenne Muscular Dystrophy is an uncommon genetic disorder characterized by progressive muscle weakening and damage due to the absence of dystrophin protein, typically commencing at an early age. Presently, no approved treatments specifically target exon 44.
Currently, undergoing evaluation in the Phase 1/2 EXPLORE44™ clinical trial, AOC 1044 is intended for individuals affected by DMD44 and represents the initial among numerous AOC compounds under development by Avidity to address Duchenne Muscular Dystrophy treatment. Avidity’s schedule includes the release of findings from the healthy volunteer segment of the EXPLORE44 trial in Q4 2023, while simultaneously enrolling DMD44 patients for the study. Notably, in April 2023, AOC 1044 was granted FDA Fast Track status for DMD44 therapy.
AOC 1044 has been meticulously engineered to transport phosphorodiamidate morpholino oligomers (PMOs) to the muscles of the skeletal and cardiac systems. Its primary objective is to selectively omit exon 44 from the dystrophin gene, thereby fostering the production of dystrophin in individuals grappling with Duchenne Muscular Dystrophy marked by exon 44-skippable mutations (DMD44). The defining feature of Duchenne Muscular Dystrophy is gradual muscle deterioration and frailty, attributed to modifications in dystrophin—a protein pivotal in shielding muscle cells from damage during contraction. AOC 1044 comprises an exclusive monoclonal antibody that attaches to transferrin receptor 1 (TfR1) and is fused with a PMO directed at exon 44.
We are pleased that the FDA has granted both Orphan Drug and Fast Track designation to AOC 1044, highlighting the importance of advancing new treatments for people living with DMD. There are currently no treatment options that target the underlying cause of DMD44. AOC 1044 is designed to specifically skip exon 44 of the dystrophin gene to enable the production of functional dystrophin protein. We look forward to advancing AOC 1044 in clinical development and bringing this very important treatment to patients as quickly and safely as possible. Steve Hughes, M.D., chief medical officer at Avidity.
The EXPLORE44 trial, a Phase 1/2 clinical study, employs a randomized, double-blind, placebo-controlled design to investigate the potential of AOC 1044. This trial encompasses both healthy volunteers and individuals harboring DMD mutations amenable to exon 44 skipping (DMD44). The primary objectives of EXPLORE44 encompass the evaluation of safety, tolerability, pharmacokinetics, and pharmacodynamic impacts of intravenous administration of AOC 1044 at various ascending dosages, encompassing both single and multiple doses. This trial is projected to encompass approximately 40 healthy volunteers and 24 participants, ranging in age from seven to 27 years old, who exhibit DMD44. EXPLORE44 will scrutinize the outcomes of exon skipping and the levels of dystrophin protein within the cohort of DMD44 participants. Moreover, those individuals afflicted with DMD44 will be given the opportunity to participate in an extension study as part of the trial.
Duchenne Muscular Dystrophy is a devastating genetic disorder that primarily affects young boys. Duchenne Muscular Dystrophy stands as the most prevalent form of muscular dystrophy. It is characterized by progressive muscle degeneration and weakness due to the absence of a protein called dystrophin, which plays a crucial role in maintaining the structural integrity of muscle fibers. As a result, affected individuals experience difficulties in walking, moving, and performing daily tasks as their muscles gradually weaken. It primarily affects males, with one in 3,500 to 5,000 boys born worldwide having Duchenne Muscular Dystrophy. While there is currently no cure for Duchenne Muscular Dystrophy, advancements in medical research have led to the development of therapies aimed at managing the symptoms and improving the quality of life for affected individuals. These include approaches such as exon skipping and gene therapy, which seek to restore the production of functional dystrophin protein or its equivalents.
CanariaBio Receives FDA’s Orphan Drug Designation for MAb-AR20.5 Targeting Pancreatic Cancer
CanariaBio Inc. announced on August 21, 2023, that the U.S. Food and Drug Administration (FDA) has officially designated its investigational drug product, MAb-AR20.5, as an orphan drug designation. MAb-AR20.5 is a murine monoclonal antibody of the IgG1k type, designed to selectively bind to the circulating and tumor-associated antigen (MUC1), which is present universally on Pancreatic Cancer cells. This achievement is noteworthy as it represents the inaugural monoclonal antibody aimed at Mucin 1 (MUC1) to be granted orphan drug designation for Pancreatic Cancer.
“Receiving Orphan Drug Designation for MAb-AR20.5 is a significant milestone for CanariaBio Inc. and speaks to the potential promise of this novel therapeutic approach,” said Mike Na, the CEO of CanariaBio Inc. “We are deeply committed to advancing innovative treatments for patients with Pancreatic Cancer and remain hopeful that MAb-AR20.5 will offer a new lifeline for those affected.”
The MAb-AR20.5 has shown potential in early studies, by inducing MUC-1-specific immune responses in cancer patients with advanced disease. This specific targeting aims to provide a more focused and potentially more effective treatment strategy for patients diagnosed with this aggressive disease. CanariaBio Inc. is planning to initiate clinical trials to assess the safety and efficacy of MAb-AR20.5 in patients with Pancreatic Cancer. More details about the upcoming studies and trial sites will be made available in the coming months.
In initial investigations, MAb-AR20.5 has exhibited promise by eliciting immune responses tailored to MUC-1 in individuals with advanced-stage cancer. This precise targeting approach strives to offer a more concentrated and potentially enhanced therapeutic approach for individuals confronting this aggressive ailment. CanariaBio Inc. is in the process of preparing to commence clinical trials aimed at evaluating the safety and effectiveness of MAb-AR20.5 in individuals diagnosed with Pancreatic Cancer. The CanariaBio will provide further information regarding the upcoming research endeavors and the locations of the trials in the forthcoming months.
Pancreatic Cancer remains one of the most challenging malignancies to treat, with limited therapeutic options available. As per DelveInsight, the total incident cases of Pancreatic Cancer in the 7MM were 180,000 in 2022, which is expected to increase in the upcoming years. In 2022, Germany had the highest number of cases, accounting for 30% of cases in EU4 and the UK. Whereas, Spain accounted for the least number of cases in the EU4 and the UK region. While, Japan accounted for 45,000 incident cases of Pancreatic Cancer, which was approximately 25% of the total Pancreatic Cancer cases in 7MM. Globally, several companies are actively working in the Pancreatic Cancer therapeutics market to improve the treatment dynamics.
