Introduction: A New Era in Therapeutics
The global TIDES (peptides and oligonucleotides) field is witnessing remarkable advancements, with recent developments spanning from groundbreaking oral peptides demonstrating exceptional clinical results to innovative RNAi therapies capable of crossing the blood-brain barrier. These breakthroughs are reshaping treatment paradigms across multiple disease areas.
Icotrokinra: Redefining Psoriasis Treatment with Oral Peptides
The Lancet recently published results from two Phase 3 trials (ICONIC-ADVANCE 1 and 2) demonstrating the impressive potential of icotrokinra, an innovative targeted oral peptides therapy for moderate-to-severe plaque psoriasis. The data revealed that 55%-57% of patients achieved at least 90% improvement in their Psoriasis Area and Severity Index (PASI 90) by week 16, with over 30% achieving complete skin clearance across different measures.
Icotrokinra represents a significant advancement in oral peptides technology, selectively blocking the IL-23 receptor (IL-23R) that plays a crucial role in activating pathogenic T cells in psoriasis. Its high-affinity binding to IL-23R and potent selective inhibition of IL-23 signaling in human T cells earned it recognition as one of Drug Hunter’s 2024 “Top 10 Molecules of the Year.”
The therapy significantly outperformed placebo, with 68% and 70% of patients achieving Investigator’s Global Assessment (IGA) scores of 0 or 1 (clear or almost clear skin) in the two studies, compared to just 11% and 9% in placebo groups.
Beyond Dermatology: The Potential of Oral Peptides for Neurodegenerative Diseases
While current applications focus on dermatological conditions, researchers are increasingly exploring the potential of oral peptides for Alzheimer’s disease and oral peptides for Parkinson’s disease. The success of icotrokinra demonstrates that oral peptide therapies can achieve significant biological effects, opening possibilities for similar approaches in neurological disorders. The development of effective oral peptides for Alzheimer’s disease could revolutionize treatment accessibility for millions of patients worldwide.
MET-097i: A New Contender in Weight Management
Metsera announced positive topline results from two Phase 2b trials (VESPER-1 and VESPER-3) for MET-097i, their ultra-long-acting GLP-1 receptor agonist. The data was compelling enough to prompt Pfizer’s acquisition agreement with Metsera in September.
In VESPER-1, patients receiving 1.2 mg of MET-097i weekly achieved a placebo-adjusted average weight loss of 14.1% at 28 weeks, with individual maximum weight reduction reaching 26.5%. Exploratory analysis showed continued weight loss beyond 36 weeks without reaching a plateau. VESPER-3 demonstrated the potential for monthly dosing with a favorable safety profile, showing remarkably low diarrhea signals and reduced nausea and vomiting risks compared to placebo.
Vutrisiran: Expanding Benefits in ATTR Amyloidosis
Alnylam Pharmaceuticals presented new analyses from their Phase 3 HELIOS-B trial showing that RNAi therapy Amvuttra (vutrisiran) reduced gastrointestinal events by 42% overall in patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM). Consistent benefits were observed across different patient subgroups, including those receiving monotherapy (37% reduction) and patients previously treated with tafamidis (49% reduction).
Vutrisiran utilizes Alnylam’s enhanced stabilization chemistry GalNAc-conjugate delivery platform to target and silence specific mRNA, blocking production of both wild-type and mutant transthyretin protein.
Breaking Barriers: RNAi Therapeutics Reach the Brain
Aerska emerged with $21 million in seed funding to develop systemically delivered RNAi therapies for brain disorders. Their antibody-oligonucleotide conjugate platform employs “brain shuttles” to cross the blood-brain barrier—a significant challenge for genetic medicines targeting the central nervous system.
The company is strategically combining external collaborations with internal innovation to advance precision medicine-oriented neurology drug development. Their initial focus includes genetic forms of Alzheimer’s and Parkinson’s disease, areas where researchers are also investigating oral peptides for Parkinson’s disease as alternative treatment approaches. The exploration of oral peptides for Alzheimer’s disease and other neurological conditions represents a parallel pathway to address these challenging disorders.
Future Outlook
These developments highlight the expanding therapeutic potential of peptides and oligonucleotides across diverse medical fields. From transforming psoriasis care to potentially addressing neurological conditions through novel approaches including oral peptides for Parkinson’s disease, the TIDES field continues to push the boundaries of what’s possible in medicine, offering new hope for patients with challenging conditions.