Rayoqta (abicipar pegol) / Molecular Partners - LARVOL DELTA

Computational modeling of anti-VEGFA drug interactions with VEGF-A: Insights into therapeutic strategies for neovascular AMD. (PubMed, Comput Biol Chem) - "In this study, we performed the first integrated in silico evaluation of six clinically relevant anti-VEGF drugs: abicipar, aflibercept, bevacizumab, brolucizumab, faricimab, and ranibizumab. This systematic analysis highlights the coexistence of evolutionary conservation and rational molecular engineering as complementary strategies shaping anti-VEGF drug performance. Overall, our findings demonstrate that computational modeling offers a cost-effective and predictive tool to guide the optimization of current therapies and the rational design of next-generation anti-VEGF agents for nAMD and other retinal vascular disorders."

Journal • Age-related Macular Degeneration • Cardiovascular • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Intraocular Inflammation, Safety Events, and Outcomes After Intravitreal Injection of Ranibizumab, Aflibercept, Brolucizumab, Abicipar Pegol, and Faricimab for nAMD. (PubMed, J Vitreoretin Dis) - " Abicipar pegol and brolucizumab were associated with a higher incidence of ocular AEs in phase 3 randomized controlled trials. The potential benefits of these drugs should be weighed against the AEs."

Clinical • Journal • Review • Age-related Macular Degeneration • Diabetic Retinopathy • Inflammation • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis • Vasculitis • Wet Age-related Macular Degeneration

Intraocular drugs: pharmacokinetic strategies and the influence on efficacy and durability. (PubMed, Expert Opin Drug Metab Toxicol) - "Durability strategies include inhibiting additional pathways (faricimab), increasing molar dose (abicipar, brolucizumab, faricimab, and aflibercept 8 mg), and prolonging the intravitreal half-life (abicipar and KSI-301). Recent phase 3 trials demonstrated modest improvements in durability, but failures that might be attributed to these strategies (conjugation and manufacturing processes) have occurred. Future drug development focuses on extending duration of action with implantable reservoirs (ranibizumab port delivery system), sustained release devices (tyrosine kinase inhibitors), and gene therapy."

Journal • PK/PD data • Review • Gene Therapies

Differential diagnosis of endophthalmitis after intravitreal drug injection for age related macular degeneration: Sterile vs. infectious. (PubMed, Arch Soc Esp Oftalmol (Engl Ed)) - "The recent release of brolucizumab and the development of new antiangiogenic molecules as abicipar pegol has increased the interest towards inflammatory complications after intravitreal drug injection. If the cause of the inflammation is uncertain we must follow up the patient closely or "tap and inject" antimicrobial agents in order to prevent the eventual complications of an infectious endophthalmitis. On the other hand, sterile endophthalmitis might be observed in mild cases or treated with steroids according to the severity of the inflammation."

Journal • Review • Age-related Macular Degeneration • Inflammation • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Pain • Retinal Disorders • Uveitis • Vasculitis

Impact of Modifying Abicipar Manufacturing Process in Patients with Neovascular Age-Related Macular Degeneration: MAPLE Study Results. (PubMed, Clin Ophthalmol) - "Abicipar produced using a modified manufacturing process showed a moderately lower incidence and severity of IOI compared with Phase 3 abicipar studies. Beneficial effects of treatment were demonstrated."

Clinical • Age-related Macular Degeneration • Inflammation • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Vasculitis • Wet Age-related Macular Degeneration

Modern trends in anti-VEGF therapy for age-related macular degeneration (PubMed, Vestn Oftalmol) - "Subsequently, a molecule with a similar mechanism of action was developed and named ranibizumab, which is a humanized monoclonal Fab fragment; it was specifically designed for ophthalmology...Aflibercept and conbercept are recombinant fusion proteins that act as soluble decoy receptors for VEGF family proteins...Simultaneously with studying brolucizumab, another study was conducted involving Abicipar pegol, but that drug showed a high rate of complications. The latest drug registered for the treatment of neovascular AMD is faricimab. The molecule of this drug is a humanized immunoglobulin G antibody that acts on two key points of angiogenesis: VEGF-A and angiopoietin-2 (Ang-2). Thus, the strategy for advancing anti-VEGF therapy lies in the development of molecules with greater efficiency (better effect on newly formed vessels leading to resorption of exudate in the retina, under the neuroepithelium and under the retinal pigment epithelium), which allows not just to..."

Journal • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Novel approach to antiangiogenic factors in age-related macular degeneration therapy. (PubMed, Cent Eur J Immunol) - "Among the directions in dry AMD treatment, the most promising are complement cascade inhibitors and complement cascade targeted gene therapy. In the article we outline the main directions in up-to-date experimental and practical approaches to wet and dry AMD therapy with the emphasis on antiangiogenic factors and gene therapy focused on the inhibition of pathological angiogenesis."

Journal • Review • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Comparative Effectiveness of Intravitreal Anti-Vascular Endothelial Growth Factor Therapies for Managing Neovascular Age-Related Macular Degeneration: A Meta-Analysis. (PubMed, J Clin Med) - "This review sought to provide further scientific evidence about the visual outcomes and treatment burden among the currently available anti-VEGF agents and regimens, including aflibercept, ranibizumab, abicipar and brolucizumab. The retrieved data did not enable other regimens or newer anti-VEGF agents such as brolucizumab to be compared. In conclusion, the T&E regimens were shown to be the most efficient, optimizing durable effectiveness whilst minimizing the IVI number in newly diagnosed exudative AMD, with aflibercept requiring the lowest IVI number."

HEOR • Journal • Retrospective data • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Thermostable designed ankyrin repeat proteins (DARPins) as building blocks for innovative drugs. (PubMed, J Biol Chem) - "We then transferred the Asp17Leu mutation to various backgrounds, including clinically validated DARPin domains, such as the VEGF-binding domain of the DARPin abicipar pegol. Interestingly, this beneficial Asp17Leu mutation is present in the N- terminal caps of three of the five DARPin domains of ensovibep, a SARS-CoV-2 entry inhibitor currently in clinical development, indicating this mutation could be partly responsible for the very high melting temperature (>90°C) of this promising anti-COVID-19 drug. Overall, such N-terminal capping repeats with increased thermostability seem to be beneficial for the development of innovative drugs based on DARPins."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effect of Anti-VEGF Therapy on the Disease Progression of Neovascular Age-Related Macular Degeneration: A Systematic Review and Model-Based Meta-Analysis. (PubMed, J Clin Pharmacol) - "Randomized, controlled trials that had at least one arm with an anti-VEGF (aflibercept, abicipar, bevacizumab, brolucizumab, pegaptanib, or ranibizumab), a control arm of placebo or anti-VEGF, a treatment duration of at least 4 months, reported best-corrected visual acuity data, and at least 20 patients were included. Results demonstrate the feasibility of Q12 dosing with clinically meaningful letter gains for abicipar and brolucizumab. The model developed under this MBMA has utility for exploring different regimens for existing or novel anti-VEGF agents."

Journal • Retrospective data • Review • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Pipeline therapies for neovascular age related macular degeneration. (PubMed, Int J Retina Vitreous) - "Prior treatments have included focal laser therapy, verteporfin (Visudyne, Bausch and Lomb, Rochester, New York) ocular photodynamic therapy, transpupillary thermotherapy, intravitreal steroids and surgical excision of choroidal neovascular membranes. Currently, the major therapies in AMD focus on the VEGF-A pathway, of which the most common are bevacizumab (Avastin; Genentech, San Francisco, California), ranibizumab (Lucentis; Genentech, South San Francisco, California), and aflibercept (Eylea; Regeneron, Tarrytown, New York)...Cheaper alternatives, including ranibizumab biosimilars, include razumab (Intas Pharmaceuticals Ltd., Ahmedabad, India), FYB 201 (Formycon AG, Munich, Germany and Bioeq Gmbh Holzkirchen, Germany), SB-11 (Samsung Bioepsis, Incheon, South Korea), xlucane (Xbrane Biopharma, Solna, Sweden), PF582 (Pfnex, San Diego, California), CHS3551 (Coherus BioSciences, Redwood City, California). Additionally, aflibercept biosimilars under development include..."

Journal • Review • Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Molecular Features of Classic Retinal Drugs, Retinal Therapeutic Targets and Emerging Treatments. (PubMed, Pharmaceutics) - "The anti-VEGF molecules include Bevacizumab, Pegaptanib, Ranibizumab, Aflibercept, Conbercept, Brolucizumab, Abicipar-pegol and Faricimab. The corticosteroids approach is mainly based on the employment of triamcinolone acetonide, dexamethasone and fluocinolone acetonide molecules...Furthermore, several new molecules are currently under investigation. Intravitreal drugs focus their activity on a wide range of therapeutic targets and are safe and efficacy in managing retinal diseases."

Journal • Review • Ophthalmology • Retinal Disorders

Molecular Partners to Regain Global Rights to Abicipar (GlobeNewswire) - "Molecular Partners AG...announced today the receipt of notification from its partner, AbbVie Inc., regarding its termination of the license and collaboration agreement for the investigational drug abicipar pegol for the treatment of neovascular age-related macular degeneration (nAMD) and Diabetic Macular Edema (DME). As such, Molecular Partners will regain the development and commercial rights of abicipar on a worldwide basis."

Licensing / partnership • Age-related Macular Degeneration • Diabetic Macular Edema • Ophthalmology

"$MOLN Molecular Partners to Regain Global Rights to Abicipar https://t.co/ya8SqSYeKQ" (@stock_titan)

"$ABBV terminates license and collaboration agreement with $MOLN for abicipar pegol for neovascular age-related macular degeneration (nAMD) and Diabetic Macular Edema (DME)." (@BioStocks)

Age-related Macular Degeneration • Diabetic Macular Edema • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Vascular Endothelial Growth Factor Antagonists: Promising Players in the Treatment of Neovascular Age-Related Macular Degeneration. (PubMed, Drug Des Devel Ther) - "Abicipar pegol, a designed ankyrin repeat protein (DARPin), demonstrated the ability to maintain stable visual acuity with 12-week dosing, but was not approved by the FDA due to higher than usual rates of intraocular inflammation. Conbercept, a recombinant anti-VEGF fusion protein, has been approved in China, and is in Phase 3 trials globally. KSI-301 is an anti-VEGF antibody biopolymer conjugate that allowed 66% of nAMD patients to maintain at least a 6-month treatment-free interval in Phase 1b studies. OPT-302, an inhibitor of VEGF-C/D, will be tested in phase 3 studies that compare anti-VEGF-A monotherapy against combination therapy with OPT-302. Faricimab is a bispecific anti-VEGF/Ang-2 antibody that upregulates the Tie-2 signaling pathway and promotes vascular stability; it is undergoing phase 3 trials with potential for 12- or 16-week dosing. PAN-90806 is a topical anti-VEGF agent that showed the ability to reduce injection frequency by 79% compared to ranibizumab..."

Journal • Review • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Gene Therapies • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • VEGFC

Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review. (PubMed, Int J Retina Vitreous) - "The main factors which play a role in intraocular inflammation after anti-VEGF injection can be divided into three causes: patient-specific, medication-specific and delivery-specific. The majority of clinically significant inflammation seen after intravitreal injection is an acute onset inflammatory response with most patients recovering baseline VA in 3-5 weeks. The presence of pain, hypopyon, severe anterior chamber reaction, hyperemia and significant vision loss may help distinguish infectious from non-infectious etiologies of post injection inflammation. Avoiding temperature fluctuation, mechanical shock, agitation during transport and handling of syringes/drugs, and the use of SO-free syringes may help minimize intraocular inflammation. While a definitive mechanism has not yet been established, current knowledge of the clinical presentation and vitreous histopathology of brolucizumab-retinal vasculitis favors an auto-immune type IV hypersensitivity reaction."

Journal • Review • Complement-mediated Rare Disorders • Immunology • Inflammation • Ocular Infections • Ocular Inflammation • Ophthalmology • Pain • Uveitis

[VIRTUAL] Ocular Inflammatory and Retinal Vascular Occlusive Adverse Events of Intravitreal anti-VEGF Injections: A Systematic Review and Network Meta-analysis (ARVO 2021) - "IR of vascular occlusions ranged from 0.085% (8/9460) for ranibizumab to 0.95% (8/841) for bevacizumab. The reported rates of OAE are generally low across the different anti-VEGFs but appear higher for newer agents brolucizumab and especially, abicipar. Further trials are needed to adequately assess their safety profile."

Adverse events • Retrospective data • Review • Age-related Macular Degeneration • Macular Degeneration • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Uveitis • Wet Age-related Macular Degeneration

[VIRTUAL] Duration of Effect of a Single Intravitreal Injection of a Sustained-Release Formulation of Abicipar Pegol Compared to a Bolus Dose of Aflibercept in a Rabbit Model of Persistent Retinal Vascular Leak (ARVO 2021) - "These data demonstrate that a single IVT injection of abicipar SR was well tolerated in NZW rabbits and suppressed retinal leak for 6 months. Compared to aflibercept, abicipar SR was at least twice as durable with a minimum of 14 additional weeks of activity."

Preclinical • Ocular Inflammation • Ophthalmology • CD31

Drug-related adverse effects of antivascular endothelial growth factor agents. (PubMed, Curr Opin Ophthalmol) - "Newer anti-VEGF agents pose a significant risk of adverse events not seen with routine anti-VEGF agents."

Adverse events • Journal • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Retinal Disorders

Drug-related adverse effects of antivascular endothelial growth factor agents. (PubMed, Curr Opin Ophthalmol) - "Newer anti-VEGF agents pose a significant risk of adverse events not seen with routine anti-VEGF agents."

Adverse events • Journal • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Retinal Disorders

Re: Kunimoto et al.: Efficacy and safety of abicipar in neovascular age-related macular degeneration: 52-week results of phase 3 randomized controlled study (Ophthalmology. 2020:127:1331-1334). (PubMed, Ophthalmology) - No abstract available

Clinical • Journal • P3 data • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Two-Year Results of the Phase 3 Randomized Controlled Study of Abicipar in Neovascular Age-Related Macular Degeneration. (PubMed, Ophthalmology) - "Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable to that with ranibizumab (0.8% and 2.3% vs 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden."

Clinical • Journal • P3 data • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Diabetic Retinopathy • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

[VIRTUAL] Evaluation of all patients with post-injection inflammation in the abicipar phase II MAPLE trial (EURETINA 2020) - "This first-time report describes the courses of all 11 patients that developed IOI following abicipar injection for nAMD during the MAPLE trial. BCVA improved at the final visit in most eyes and inflammation completely resolved in all eyes. Abicipar produced through a modified manufacturing process demonstrated much improved safety compared to the abicipar used in the combined Phase 3 studies."

Clinical • P2 data • Complement-mediated Rare Disorders • Immunology • Inflammation • Ocular Infections • Ocular Inflammation • Ophthalmology • Uveitis

[VIRTUAL] Abicipar for nAMD Provides Faster Retinal Fluid Resolution and Achieved Similar Dryness through Week 104 with Fewer Injections (EURETINA 2020) - "Abicipar Q8 and Q12 showed faster initial clearance of subretinal, intraretinal, and any fluid compared to rQ4 group. The percent of patients with dry retinas at Week 104 were similar for each arm with fewer injections for abicipar Q8 (14 injections) and Q12 (10 injections) vs ranibizumab Q4 (25 injections)."

Ophthalmology