P3, N=21, Completed, PharmaEssentia Japan K.K. | Recruiting --> Completed

P3, N=67, Recruiting, PharmaEssentia Japan K.K. | Trial completion date: Oct 2024 --> Jun 2026 | Trial primary completion date: Oct 2024 --> Jun 2026

P4, N=70, Not yet recruiting, PharmaEssentia | N=110 --> 70 | Trial completion date: Feb 2027 --> Jun 2026 | Initiation date: Jul 2024 --> Jan 2025

P3, N=111, Active, not recruiting, PharmaEssentia | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Jul 2025 | Trial primary completion date: Jan 2024 --> Dec 2024

P2, N=91, Active, not recruiting, PharmaEssentia | Recruiting --> Active, not recruiting | N=64 --> 91 | Trial completion date: Dec 2026 --> Mar 2027 | Trial primary completion date: Jul 2024 --> Mar 2027

This study demonstrates the versatility of in silico analysis to determine molecular function of large macromolecular complexes such as the spliceosome CC. Furthermore, our analysis indicates that therapeutic lowering of CC levels in colon cancer patients may enhance patient survival.

Whole exome sequencing revealed loss of function mutations in TP53, STK11, PBRM1, SMAD3, FN1, NTRK1, and FANCD2, as well as gain of function mutations in MTOR, BCL11A and COL1A1, along with amplification of CCND3 and MDM2. This mutational landscape halfway between thymic carcinoma (TP53, PBRM1) and hepatoid variant carcinoma of other sites (STK11) suggests that, at some point during carcinogenesis, a switch occurred from an epithelial thymic phenotype to a hepatoid-like one.

Interestingly, the reduction in JAK2 VAF from baseline was linearly associated with the reduction in NLR. Patients who failed Phl-O at 12 months had characteristics that distinguished them from responders, including very high NLR and resistance to cross-over to 100 μg Ropeg every 2 weeks suggesting higher escalated doses of Ropeg. In conclusion, the study provides evidence that NLR can serve as a valuable biomarker to assess and guide treatment with Ropeg in the early stage of low-risk PV patients.

All patients experienced adverse events; 25/27 (92.6%) experienced adverse drug reactions (ADRs), but no serious ADRs or deaths occurred. This interim analysis demonstrated the safety and efficacy of ropegIFN over 36 months in Japanese patients with PV.

P3, N=150, Not yet recruiting, PharmaEssentia | Trial completion date: Aug 2027 --> Apr 2028 | Trial primary completion date: Jun 2026 --> Mar 2027

P2, N=11, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Nov 2023 | Trial primary completion date: Aug 2024 --> Nov 2023

P1, N=100, Recruiting, Nammi Therapeutics Inc

P3, N=117, Recruiting, AOP Orphan Pharmaceuticals AG

P=N/A, N=319, Recruiting, FROM- Fondazione per la Ricerca Ospedale di Bergamo- ETS

In addition, the results of ingenuity pathway analysis demonstrated the inhibition of T lymphocyte function, including differentiation, movement, and infiltration. Our results, for the first time, delineate the mechanisms underlying the immunotoxicity of BHPF in human lymphocytes.

All patients experienced treatment-emergent adverse events (TEAEs) related to ropeginterferon alfa-2b, but no grade ≥ 3 TEAEs or deaths related to ropeginterferon alfa-2b occurred, and no new safety concerns arose. This analysis indicated that ropeginterferon alfa-2b may be an effective treatment option for Japanese patients with low-risk PV.

P3, N=150, Not yet recruiting, PharmaEssentia

There is currently lack of information on the real-world patient selection, including the impact of local reimbursement policies, and drug management, particularly: type/timing of screening and follow-up tests; absolute/relative contraindications to therapy; ropegIFNα2b dose and combinations with hydroxyurea. This real-world experience suggests a significant impact of local regulations on drug prescription and the need for greater real-world data collection on ropegIFNα2b in PV patients. Also, it describes appropriate multidisciplinary screening and monitoring procedures during ropegIFNα2b therapy.

P3, N=1673, Active, not recruiting, National Cancer Institute (NCI)

The propositus was not controlled by hydroxyurea, and JAK2 inhibitors were not tolerated; however, Ropeginterferon-alfa-2b (Ropeg-IFN-α) induced a remission. We report dominantly inherited erythrocytosis secondary to a novel germline JAK2R715T gain-of-function mutation with many but not all comparable molecular features to JAK2V617F PV. We also document a previously unreported inhibitory mechanism of JAK2 signaling by Ropeg-IFN-α.

P3, N=134, Completed, National Taiwan University Hospital | Active, not recruiting --> Completed

Overall, this study provided valuable information on the ethnics- and genetics-based algorithm in the treatment of MPN.

P2, N=49, Active, not recruiting, PharmaEssentia | Trial completion date: Apr 2024 --> May 2025

P2, N=88, Active, not recruiting, National Cancer Institute (NCI)

Recent regulatory approvals in polycythemia vera (PV) include the JAK inhibitor ruxolitinib, and more recently, a novel recombinant interferon alfa-2 (IFN-α) therapeutic agent. More recently, a novel pegylated IFN-α, ropeginterferon alfa-2b, received approval for PV by the European Medicines Agency and the US Food and Drug Administration in 2019 and 2021, respectively. This article reviews the clinical research and recent advances that led to the first regulatory approval of IFN-α in a BCR/ABL-negative MPN and its future promise as a disease-modifying therapeutic agent.

P4, N=110, Not yet recruiting, PharmaEssentia

A Phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in patients with HCC recurrence who underwent curative surgery for HBV-related HCC. The treatment modality was well tolerated. These data support the further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

In addition, the chimeric form had reduced cytotoxicity towards Vero cells and increased cell viability under viral load conditions compared with commercial IFN-a2b preparations. Analysis of the pharmacokinetic profile of ryIFN-ApoA-I after a single subcutaneous injection in mice showed a 1.8-fold increased half-life of the chimeric protein compared with ryIFN.

Side effects were observed in one patient (6.2%). Our experience is in support of previous studies regarding ropeginterferon alfa-2b efficacy and safety profile in the treatment of young patients with Ph- MPNs.

P3, N=1345, Active, not recruiting, National Cancer Institute (NCI)

P4, N=480, Recruiting, The First Affiliated Hospital of Medical College of Zhejiang University; The First Affiliated Hospital of Medical College of Zhejiang University | Phase classification: P3 --> P4 | N=320 --> 480

Background: Prior to the approval of ropeginterferon alfa-2b-njft (ropeginterferon) in November 2021, the alternatives to hydroxyurea for the treatment of polycythemia vera (PV) included Janus Kinase inhibitors (JAKi) and older versions of recombinant interferon-alpha (rIFNα). This study examined FAERS reports to detect disproportional reporting odds of drug-associated AEs severity and SOCs in four PV treatments: ropeginterferon, ruxolitinib, interferon alfa-2a, and pacritinib. Ropeginterferon had a significant ROR for non-serious AEs. Peginterferon alfa-2a demonstrated a significant ROR for SAEs.

Most patients with PV receive phlebotomy and low-dose aspirin to prevent thrombosis...Treatment-naïve patients and those pretreated with hydroxyurea (HU) will be included...General statistical summaries will be applied to primary and secondary endpoints. For categorical variables, frequency and percentage will be presented with a 95% confidence interval.

P3, N=174, Active, not recruiting, PharmaEssentia | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Nov 2024

P1, N=90, Recruiting, Mongolian National University of Medical Sciences

No abstract available

In essential thrombocythemia, ropeginterferon alfa-2b is being evaluated, as are therapies to modify epigenetics and inhibit CALR. The enhanced focus on MPNs brings hope that our field can improve morbidity and mortality in this group of diseases.

Ropeginterferon alfa-2b(P1101) showed it was more effective in achieving durable hematological and molecular remissions than hydroxyurea and well tolerated during long-term application. The updated data showed consistent results with the previous 2022 ASH meeting abstract that ropeginterferon alfa-2b therapy, with rapid dose optimization, induced hematological response, reduced JAK2 allele burden, and was well tolerated in Korean patients. Moreover, we clarified the association between efficacy and MR as assessed by reduction in JAK2 allele burden. More data will be updated during the meeting.

These observations indicate that TYK2 is essential for the effects of IFN-α on HSCs. These results indicate that TYK2 is indispensable for the effects of IFN-α on improvement of MPN features.

The model compared ropeginterferon alfa-2b-njft used either as first- or second-line versus an alternative treatment pathway of first-line hydroxyurea followed by ruxolitinib. A younger patient age at baseline and a higher percentage of patients with low-risk disease improved the cost-effectiveness of ropeginterferon alfa-2b-njft. Ropeginterferon alfa-2b-njft is a cost-effective treatment option for a broad range of patients with PV, including both low- and high-risk patients and patients with and without prior cytoreductive treatment with hydroxyurea.