- |||||||||| Lynparza (olaparib) / Merck (MSD), AstraZeneca
Journal, BRCA Biomarker, PARP Biomarker: Activated NAD+ biosynthesis pathway induces olaparib resistance in BRCA1 knockout pancreatic cancer cells. (Pubmed Central) - Apr 20, 2024 Upregulation of intracellular NAD+ levels by the addition of nicotinamide also induced resistance to olaparib and talazoparib in C1 cells. Taken together, our findings suggest that upregulation of intracellular NAD+ is one of the factors underlying the acquisition of PARP inhibitor resistance.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Talzenna (talazoparib) / Pfizer, Tecentriq (atezolizumab) / Roche
Retrospective data, Review, Journal, BRCA Biomarker, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker, Metastases: Efficacy and safety of first-line treatment for metastatic triple-negative breast cancer: A network meta-analysis. (Pubmed Central) - Apr 11, 2024 For PD-L1 and BRCA mutation-positive tumors, atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib is an effective treatment option. Neutropenia, diarrhea, and fatigue are frequently occurring serious adverse events.
- |||||||||| Palynziq (pegvaliase-pqpz) / BioMarin
Journal: First successful outcomes of pegvaliase (PALYNZIQ) in children. (Pubmed Central) - Mar 26, 2024 This report addresses the potential broader applications of Pegvaliase in children, as well as its safety and tolerability in this age group. However, larger sample sizes and robust methodologies are required to validate such findings.
- |||||||||| Brineura (cerliponase alfa) / BioMarin
Journal: Intravitreal enzyme replacement for inherited retinal diseases. (Pubmed Central) - Mar 25, 2024 The evidence suggests that IVT ERT with rhTPP1 may be a safe and effective treatment for CLN2 retinopathy. However, the optimal dosage and frequency to achieve the best possible outcomes requires further investigation as does patient selection.
- |||||||||| Roctavian (valoctocogene roxaparvovec-rvox) / BioMarin
Clinical Trial,Phase II, Journal: Long-term safety and efficacy outcomes of valoctocogene roxaparvovec gene transfer up to 6 (Pubmed Central) - Mar 14, 2024 Moreover, the BMN/PAZA combination increased the immunogenicity and synergized with PD-1 antibody in improving the overall therapeutic effect in an orthotopic model of lung cancer (LLC). Valoctocogene roxaparvovec safety and efficacy profiles remain largely unchanged; genomic investigations showed no association with a parotid tumour.
- |||||||||| Therapeutic Resistance Models and Treatment Sequencing in Advanced Prostate Cancer (301B) - Mar 12, 2024 - Abstract #AUA2024AUA_3062;
These include C4-2B MDVR, C4-2B AbiR, C4-2B ApaR, C4-2B DaroR, TaxR, and 2B-olapR, which are resistant to enzalutamide, abiraterone, apalutamide, darolutamide, docetaxel, and olaparib, respectively...Conversely, cells with acquired resistance to docetaxel exhibit cross-resistance to both cabazitaxel and olaparib but retain sensitivity to NGATs like enzalutamide and abiraterone...Moreover, OlapR models display cross-resistance to other clinically relevant PARP inhibitors, including rucaparib, niraparib, and talazoparib... Our findings suggest the existence of intra cross-resistance within a drug class (i.e., within NGATs or within taxanes, or within PARPi
- |||||||||| Kuvan (sapropterin) / BioMarin, Daiichi Sankyo, Palynziq (pegvaliase-pqpz) / BioMarin
Developing a probiotic therapy for phenylketonuria using bacterial and enzyme engineering (In-person; Gravier F Ballroom (New Orleans Marriott Warehouse Arts District)) - Mar 12, 2024 - Abstract #ACSSp2024ACS_Sp_13605; While PKU patients are responsive to the FDA-approved drugs sapropterin and pegvaliase, there is room for development of new therapeutic modalities...Performing parallel studies in multiple bacterial species will allow us to assess species-specific and universal contributors of activity and expression level. Finally, we explore transporter engineering to increase phenylalanine uptake by LAB to further enhance phenylalanine conversion to trans -cinnamic acid.
- |||||||||| Review of Gene Therapy Access Landscape () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_1812;
Recently launched ultra-high-cost therapies face additional restrictions compared to lower-priced (<$3M) gene therapies. Therapies on the market longer (e.g., Luxturna, Zolgensma) employ more types of contracting strategies and face less restrictive management.
- |||||||||| Advances in Science and Challenges at HTA: The Case of CRISPR Technologies () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_1800;
Exa-cel and subsequent CRISPR-based technologies are expected to face similar challenges to other cell and gene therapies, with the risk of off-target gene editing likely to be scrutinized for many years to come. HTA agencies may be more willing to accept uncertainty around clinical benefit for products demonstrating cost savings for healthcare systems.
- |||||||||| Hemlibra (emicizumab-kxwh) / Roche, Roctavian (valoctocogene roxaparvovec-rvox) / BioMarin, Hemgenix (etranacogene dezaparvovec) / CSL Behring
A Systematic Review of Cost-Effectiveness Analyses of Gene Therapy Treatments for Hemophilia Type A and B () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_1788; OBJECTIVES: To assess the long-term value of valoctocogene roxaparvovec-rvox (hemophilia A) and etranacogene dezaparvovec (hemophilia B) use, respectively, and to evaluate the relevance, and validity of the underlying data and assumptions used in published cost-effectiveness models...Gene therapy was shown to have high initial costs, however, all included studies (three hemophilia A and one hemophilia B) showed that gene therapies had lower overall costs and better health outcomes (dominant) than factor replacement therapies and emicizumab. Even with the high upfront cost and durability uncertainties of hemophilia A and B novel gene therapy, these products can be a cost-effective use of treatment resources if the treatment effects are durable over time.
- |||||||||| Roctavian (valoctocogene roxaparvovec-rvox) / BioMarin, Hemgenix (etranacogene dezaparvovec) / CSL Behring, Upstaza (eladocagene exuparvovec) / PTC Therap
Cell and Gene Therapy Access in the US and European Countries () - Mar 8, 2024 - Abstract #ISPOR2024ISPOR_1780; Visible ex-factory prices continue to set new records raising concerns about affordability and sustainability, while the gulf between ex-factory and net prices seems to be increasing. Growing recognition and acceptance of outcomes-based payment models and real-world evidence generation to facilitate access is another trend in both the US and Europe.
- |||||||||| Firdapse (amifampridine) / BioMarin, Catalyst Pharma, Dydo Pharma
A Unique Case of Non-paraneoplastic Lambert-Eaton Myasthenic Syndrome Treated with Subcutaneous Immunoglobulin (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_4595; For LEMS patients refractory to initial symptomatic treatment with amifampridine, immunomodulatory therapy with intravenous immunoglobulin (IVIG) is often utilized...The diagnosis of non-paraneoplastic LEMS requires a high level of clinical suspicion, and prompt diagnosis is necessary to facilitate treatment. Subcutaneous immunoglobulin therapy may be a reasonable alternative for patients with LEMS who do not tolerate the intravenous formulation.
- |||||||||| Aldurazyme (laronidase) / BioMarin, Sanofi
A Case of Mucopolysaccharidosis Type 1 with Associated Papilledema Respondent to Therapy (Colorado Convention Center | Exhibit Hall B-E) - Mar 8, 2024 - Abstract #AAN2024AAN_4075; True papilledema could play a role in the symptomatic presentation of optic nerve swelling and contribute to worsening visual acuity in these patients. Other potential factors for optic disc edema include deposition of glycosaminoglycans into the ganglion cells around the optic nerves and compression of the nerves due to glycosaminoglycan deposition in the surrounding tissues, causing pseudopapilledema.
- |||||||||| Small molecule inhibitor of FEN1 nuclease utilizing a novel metal-binding pharmacophore synergizes with inhibitors of USP1, PARP, PARG and ATR (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_9420;
Synergistic relationships of BSM-1516 and its combination potential were further explored in viability studies with a panel of DDR inhibitors (n=25) in BRCA2-proficient and deficient cell lines. Strong synergy was identified with multiple drug classes that included inhibitors of USP1 (KSQ-4279), PARP (Olaparib, Niraparib, Talazoparib, AZD5305), PARG (PDD 00017273) and ATR (AZD6738, VE-822, Elimusertib).In vitro ADME assays and in vivo PK studies showed that BSM-1516 has properties suitable for in vivo testing, either as a single agent or in combination with synergistic DDR inhibitors, an investigation that is currently underway.
- |||||||||| Talzenna (talazoparib) / Pfizer, Lynparza (olaparib) / Merck (MSD), AstraZeneca
Karyopherin ?-2, a nuclear export protein, promotes cancer progression in lung adenocarcinoma (Section 28) - Mar 5, 2024 - Abstract #AACR2024AACR_9399; Strong synergy was identified with multiple drug classes that included inhibitors of USP1 (KSQ-4279), PARP (Olaparib, Niraparib, Talazoparib, AZD5305), PARG (PDD 00017273) and ATR (AZD6738, VE-822, Elimusertib).In vitro ADME assays and in vivo PK studies showed that BSM-1516 has properties suitable for in vivo testing, either as a single agent or in combination with synergistic DDR inhibitors, an investigation that is currently underway. Collectively, this study suggest that KPNA2 promotes invasiveness and metastasis and is associated with poor patient outcomes; therefore, KPNA2 will be a good therapeutic target or a biomarker in lung adenocarcinoma.
- |||||||||| pemrametostat (GSK3326595) / Ipsen, Talzenna (talazoparib) / Pfizer, Lynparza (olaparib) / Merck (MSD), AstraZeneca
PRMT5 inhibitor synergizes with PARP inhibitors in triple-negative breast cancer cells (Section 44) - Mar 5, 2024 - Abstract #AACR2024AACR_9225; Furthermore, we show that inhibiting PRMT5 in BRCA1WT cells upregulates the mRNA expression of RAD50, a DNA damage sensing gene in the HR pathway. Our ongoing study is to delineate the molecular mechanism of action for the observed synergy and whether PRMT5 inhibition can overcome resistance to PARP inhibitors.
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