The purpose of this study is:
1. To provide continued pelabresib treatment to patients who have previously received pelabresib in a parent study and continue collecting safety and efficacy information
2. To evaluate the overall survival and leukemia-free survival of patients who discontinued placebo or pelabresib treatment in pelabresib parent studies

Start Date13 Aug 2024

Sponsor / Collaborator

Constellation Pharmaceuticals, Inc.

ISRCTN10750305

/ CompletedPhase 1

An Open-Label, Single-Dose, Single-Period Study to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-pelabresib in Healthy Male Subjects

Start Date22 Nov 2022

Sponsor / Collaborator

Constellation Pharmaceuticals, Inc.

NCT05391022

/ CompletedPhase 1

A Phase 1, 2-Part Study to Evaluate the Effect of Food on Pharmacokinetics of Pelabresib (CPI-0610) and the Effect of Pelabresib on QTc in Patients With Advanced Malignancies

Phase 1 2-part study to evaluate the effect of food on pharmacokinetics of pelabresib (CPI-0610) and the effect of pelabresib on QTc in patients with advanced malignancies

Start Date20 Jul 2021

Sponsor / Collaborator

Constellation Pharmaceuticals, Inc.

100 Clinical Results associated with Pelabresib

100 Translational Medicine associated with Pelabresib

100 Patents (Medical) associated with Pelabresib

Literatures (Medical) associated with Pelabresib

01 May 2025·NATURE MEDICINE

Pelabresib plus ruxolitinib for JAK inhibitor-naive myelofibrosis: a randomized phase 3 trial

Article

Author: Mesa, Ruben ; Harrison, Claire N ; Chraniuk, Dominik ; Boxhammer, Rainer ; Gerds, Aaron T ; Lee, Sung-Eun ; Lavie, David ; Li, Qing ; Talpaz, Moshe ; Oh, Stephen T ; Lucchesi, Alessandro ; Mascarenhas, John ; Grosicki, Sebastian ; Álvarez-Larrán, Alberto ; Patriarca, Andrea ; Brown, Barbara ; Scandura, Joseph M ; Vannucchi, Alessandro M ; Abruzzese, Elisabetta ; Harris, Morgan ; Bose, Prithviraj ; Jegg, Anna-Maria ; Kays, Sarah-Katharina ; Kuykendall, Andrew T ; Gupta, Vikas ; Palandri, Francesca ; Kiladjian, Jean-Jacques ; Rampal, Raajit K

Janus kinase (JAK) inhibitors provide limited depth and durability of response in myelofibrosis. We evaluated pelabresib-a bromodomain and extraterminal domain (BET) inhibitor-plus ruxolitinib (a JAK inhibitor) compared with placebo plus ruxolitinib as first-line therapy. In this phase 3 study (MANIFEST-2), JAK inhibitor-naive patients with myelofibrosis were randomized 1:1 to pelabresib 125 mg once daily (QD; 50-175 mg QD permitted) for 14 days followed by a 7-day break (21-day cycle), or to placebo in combination with ruxolitinib 10 or 15 mg twice daily (BID; 5 mg QD-25 mg BID permitted). Primary endpoint was reduction in spleen volume of ≥35% from baseline at week 24. Key secondary endpoints were absolute change in total symptom score (TSS) and TSS50 response (≥50% reduction in TSS from baseline at week 24). The primary endpoint was met in 65.9% of patients randomized to pelabresib-ruxolitinib (n = 214) versus 35.2% to placebo-ruxolitinib (n = 216) (difference, 30.4%; 95% confidence interval (CI), 21.6, 39.3; P < 0.001). Absolute change in TSS was -15.99 versus -14.05 (difference, -1.94; 95% CI, -3.92, 0.04; P = 0.0545) and TSS50 was achieved in 52.3% versus 46.3% (difference, 6.0%; 95 CI, -3.5, 15.5) with pelabresib-ruxolitinib versus placebo-ruxolitinib. Exploratory analyses of proinflammatory cytokine amounts and bone marrow morphology showed greater improvement with the combination. Thrombocytopenia and anemia were the most common treatment-emergent adverse events, occurring in 52.8% (13.2% grade ≥3) versus 37.4% (6.1% grade ≥3) and 44.8% (23.1% grade ≥3) versus 55.1% (36.5% grade ≥3), respectively. Pelabresib in combination with ruxolitinib is well tolerated, improves signs of underlying myelofibrosis pathobiology and provides substantial clinical benefit over standard-of-care JAK inhibitor monotherapy. ClinicalTrials.gov identifier: NCT04603495 .

01 Mar 2025·HEMATOLOGICAL ONCOLOGY

Managing Myelofibrosis: Matching Advances in Treatments With Clinical Unmet Needs

Review

Author: Chan, Tze Wei ; Than, Hein ; Billa, Gauri ; Huang, Feng‐Ju ; Lee, Lai Heng

ABSTRACT:

Myelofibrosis (MF) is characterized by anemia, constitutional symptoms, hepatosplenomegaly and bone marrow fibrosis, and is associated with poor survival. The janus kinase inhibitor (JAKi) ruxolitinib has been the mainstay of treatment for over a decade. Despite demonstrated symptomatic and quality of life improvement, unmet clinical needs persist. A literature review identified promising novel targeted treatment options in MF using pre‐set selection criteria (available Phase 2 or 3 data, minimum enrollment of 50 patients, trial end date within the last 5 years). Available data for novel and approved therapies were extracted, tabulated, and analyzed for clinical relevancy. From an initial shortlist of 48, 16 retained molecules were selected for inclusion. Other JAKi (pacritinib, momelotinib, jaktinib) address treatment‐related cytopenia, expanding the therapeutic utility of this class of agents to patients with baseline anemia or thrombocytopenia. Novel candidates exploit multiple molecular pathways, and offer the potential to improve the management of MF‐associated cytopenia (imetelstat, pelabresib, navitoclax, selinexor, luspatercept, sotatercept, elritercept, LCL161, bomedemstat) and recover bone marrow fibrosis (imetelstat, pelabresib, navitoclax and bomedemstat). It remains to be seen if these newer agents can induce any remission in MF and enable patients to come off therapy, but the future is beginning to look much brighter.

01 Mar 2025·Current medicinal chemistry

A Combination of CPI-0610 and SAHA Induces Apoptosis through STAT3 and p38 Signalling Pathways in Diffuse Large B-cell Lymphoma Cells

Article

Author: Xu, Kailin ; Yan, Dongmei ; Xu, Linyan ; Qin, Yuanyuan ; Sang, Wei ; Liu, Mengdi ; Jiao, Jun ; Zhang, Meng

Background:::

Although immunotherapies have greatly improved diffuse large B-cell lymphoma (DLBCL) prognosis, a proportion of patients remain to be relapsed or refractory. Therefore, the identification of novel therapeutic targets and drugs is urgently required. Inhibition of the bromodomain and extra-terminal (BET) proteins has been a promising therapeutic strategy for various haematologic cancers. CPI-0610 is a potent and selective BET inhibitor. The effects of CPI-0610 in DLBCL cells have not been reported yet.

Aims::

The aim of this study was to assess the effects of CPI-0610 in DLBCL and its underlying mechanisms.

Methods::

DLBCL cells were treated with CPI-0610, followed by measuring cell viability, cell cycle, apoptosis, autophagy, and specific cell signaling pathways. Moreover, immunodeficient mice were engrafted with SUDHL2 cells and then treated with CPI-0610 for analysis of tumor burden. We also analyzed the synergistic effect of CPI-0610 with histone deacetylase inhibitor suberoylanilide hydroxamic acid.

Results::

The present study demonstrated that CPI-0610 displayed cell cytotoxicity by arresting the G1 cell cycle and inducing endogenous and exogenous apoptotic pathways. Additionally, CPI-0610 decreased BRD4 and c-Myc expressions and affected MAPK, JAK/STAT, and AKT signalling pathways in human DLBCL cells. An in vivo experiment exhibited that CPI-0610 decreased the primary tumour growth of the DLBCL xenograft model. Furthermore, the use of CPI-0610 in combination with suberoylanilide hydroxamic acid exhibited a specific synergistic effect in inducing apoptosis through the regulation of STAT3 and p38.

Conclusion::

Targeting BET may be an effective therapeutic strategy and potentiated by a combination with histone deacetylase inhibition in DLBCL.

News (Medical) associated with Pelabresib

15 May 2025

·www.globenewswire.com

New Novartis data at ASCO and EHA showcase momentum of pioneering portfolio with promising pipeline

NATALEE subanalysis evaluates Kisqali in pre-menopausal early breast cancer patients, amid rising diagnosis rates in younger patients Pluvicto analysis and Scemblix ASC4START primary endpoint results provide insights into use in earlier settingsFabhalta APPULSE-PNH full results build on Phase III program, reporting new data from expanded PNH population in adults switching from anti-C5Ianalumab Phase II data in immune thrombocytopenia and longer-term pelabresib Phase III data in myelofibrosis show breadth of pipeline in hematologic diseases Basel, May 15, 2025 – Novartis will present data from 60 company or investigator sponsored abstracts that have the potential to change clinical practice, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and the European Hematology Association (EHA) 2025 Congress. “The breadth of our oncology and hematology portfolio – anchored by Kisqali, Pluvicto, Scemblix and Fabhalta – demonstrates our leadership in both solid tumors and hematologic diseases,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer, Novartis. “At ASCO and EHA, we will present new data on these priority medicines as well as updates from our pipeline and our industry-leading radioligand therapy research.” Novartis will also highlight its US partnerships with the National Football League (NFL), Alliance for Breast Cancer Policy, and ZERO Prostate Cancer, which encourage people to make proactive decisions about their health and advance patient-centered policy solutions to help improve outcomes. “We're witnessing a profound shift in how people move through their cancer journey, with cancer diagnoses occurring at younger ages and, simultaneously, older patients living longer and approaching aging with new vigor,” said Victor Bultó, President, US, Novartis. “As a leader in driving medical advances in oncology, we have the responsibility to also make a difference in areas beyond treatment innovation. By partnering across the ecosystem, our goal is to advance the conversation around earlier detection and meet the evolving needs of this next generation of cancer patients.” Key highlights of data accepted by ASCO include: Medicine Abstract Title Abstract Number/ Presentation Details Kisqali®(ribociclib)* Efficacy and safety of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in NATALEE: Analysis across menopausal status and age Abstract #516Rapid OralJune 1, 8:00 – 9:30am CDT Kisqali®(ribociclib) Real-world (RW) analysis of characteristics and risk of recurrence (ROR) in Black patients (pts) with HR+/HER2− early breast cancer (EBC) eligible for NATALEE Abstract #527Poster PresentationJune 2, 9:00am – 12:00pm CDT Kisqali®(ribociclib) Adjuvant WIDER: A phase 3b trial of ribociclib (RIB) + endocrine therapy (ET) as adjuvant treatment (tx) in a close-to-clinical-practice patient (pt) population with HR+/HER2− early breast cancer (EBC) Abstract #TPS617Poster PresentationJune 2, 9:00am – 12:00pm CDT Kisqali®(ribociclib) First-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in clinically aggressive hormone receptor (HR)+/HER2− advanced breast cancer (ABC): A subgroup analysis of patients (pts) with or without liver metastases (mets) from RIGHT Choice Abstract #1069Poster PresentationJune 2, 9:00am – 12:00pm CDT Scemblix®(asciminib) Efficacy and safety of asciminib (ASC) in patients (pts) with chronic-phase chronic myeloid leukemia (CML-CP) after 1 tyrosine kinase inhibitor (TKI): Interim analysis (IA) of the phase 2 ASC2ESCALATE trial Abstract #6516Rapid OralMay 30, 1:00 – 2:30pm CDT Scemblix® (asciminib) Primary endpoint results of the phase 3b ASC4START trial of asciminib (ASC) vs nilotinib (NIL) in newly diagnosed chronic phase chronic myeloid leukemia (CML-CP): Time to treatment discontinuation due to adverse events (TTDAE) Abstract #6501Oral PresentationJune 2, 3:00 – 6:00pm CDT Pluvicto®(lutetium Lu 177 vipivotide tetraxetan) Clinical outcomes of prompt versus deferred 177Lu-PSMA-617 initiation for metastatic castration-resistant prostate cancer (mCRPC) based on prior androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy exposure: a real-world PRostatE Cancer dISease observatION (PRECISION) data platform analysis Abstract #e17030Online Publication Pluvicto®(lutetium Lu 177 vipivotide tetraxetan) Real-world outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) receiving guideline-recommended therapies after treatment with 177Lu-PSMA-617: a real-world PRostatE Cancer dISease observatION (PRECISION) data platform analysis Abstract #e17035Online Publication Pluvicto®(lutetium Lu 177 vipivotide tetraxetan) PSMA-delay castration (DC): An open-label, multicenter, randomized phase 3 study of [177Lu]Lu-PSMA-617 versus observation in patients with metachronous PSMA-positive oligometastatic prostate cancer (OMPC) Abstract #TPS5127Poster PresentationJune 2, 9:00am – 12:00pm CDT Key highlights of data accepted by EHA include: Medicine Abstract Title Abstract Number/ Presentation Details Fabhalta®(iptacopan) APPULSE-PNH: Oral iptacopan monotherapy demonstrates clinically meaningful hemoglobin (Hb) increases in patients (pts) with paroxysmal nocturnal hemoglobinuria (PNH) and Hb ≥10 g/dL on anti-C5 therapy Abstract #S183Oral PresentationJune 13, 5:00 – 6:15pm CEST Fabhalta®(iptacopan) The 2-year safety and efficacy of iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria (PNH) from APPLY- and APPOINT-PNH studies who entered the roll-over extension program (REP) Abstract #PF660Poster PresentationJune 13, 6:30 – 7:30pm CEST Scemblix®(asciminib) Asciminib (ASC) shows superior tolerability vs nilotinib (NIL) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): Primary endpoint results of the phase (Ph) 3b ASC4START trial Abstract #S166Oral PresentationJune 13, 5:00 – 6:25pm CEST Scemblix®(asciminib) Improved patient-reported outcomes (PROs) with asciminib (ASC) vs investigator-selected tyrosine kinase inhibitors (IS-TKIs) in newly diagnosed chronic myeloid leukemia (CML): ASC4FIRST wk 48 analysis Abstract #PS1588Poster PresentationJune 14, 6:30 – 7:30pm CEST Scemblix®(asciminib) Interim analysis (IA) results from ASC2ESCALATE support asciminib (ASC) as a treatment (Tx) option in chronic-phase chronic myeloid leukemia (CML-CP) after 1 tyrosine kinase inhibitor (TKI) Abstract #PF595Poster PresentationJune 13, 6:30 – 7:30pm CEST Pelabresib(DAK539) Pelabresib in combination with ruxolitinib for janus kinase inhibitor-naive patients with myelofibrosis: 72-week follow-up with long-term efficacy outcomes of the phase III MANIFEST-2 study Abstract #S223Oral PresentationJune 12, 5:00 – 6:15pm CEST Ianalumab(VAY736) A Phase 2 Study of Ianalumab in patients with primary immune thrombocytopenia previously treated with at least two lines of therapy (VAYHIT3) Abstract #S312Oral PresentationJune 15, 11:00am – 12:15pm CEST Rapcabtagene autoleucel (YTB323) Rapcabtagene Autoleucel (YTB323) in patients with relapsed/refractory diffuse large B-cell lymphoma: A phase II trial clinical update Abstract #PF1152Poster PresentationJune 13, 6:30 – 7:30pm CEST Novartis in oncologyThe Novartis oncology strategy focuses on people living with cancer and those who care for them, from loved ones to clinical care teams, including their providers. For the past 30+ years, the aim has been to extend and improve lives by discovering differentiated, innovative and practice-changing medicines for patients. As Novartis reimagines medicine, it collaborates with a wide range of patient advocacy groups and supports education, early cancer screening and diagnosis, all while innovating at a rate that is unparalleled in the industry. With approximately 35 research and development projects across solid tumors, hematology and radioligand therapy (RLT), Novartis is committed to using technology, leading science and patient-centered research to deliver pioneering cancer care for all those in need. DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide. Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. # # # *Kisqali was developed by Novartis under a research collaboration with Astex Pharmaceuticals. Novartis Media RelationsE-mail: media.relations@novartis.com Novartis Investor RelationsCentral investor relations line: +41 61 324 7944E-mail: investor.relations@novartis.com

Phase 2ASCOPhase 3Clinical Result

27 Mar 2025

·www.drugs.com

Pelabresib Plus Ruxolitinib Improves Underlying Myelofibrosis

THURSDAY, March 27, 2025 -- Pelabresib, a bromodomain and extraterminal domain inhibitor, plus ruxolitinib (a Janus kinase [JAK] inhibitor) improves signs of underlying myelofibrosis in JAK inhibitor-naive patients, according to a study published online March 10 in Nature Medicine . Raajit K. Rampal, M.D., Ph.D., from the Memorial Sloan Kettering Cancer Center in New York City, and colleagues conducted a phase 3 study (MANIFEST-2) involving JAK inhibitor-naive patients with myelofibrosis who were randomly assigned to receive pelabresib 125 mg once daily for 14 days followed by a seven-day break or to placebo combined with ruxolitinib 10 or 15 mg twice daily (214 and 216 patients, respectively). The researchers found that the primary end point of reduction in spleen volume of ≥35 percent from baseline at week 24 was met in 65.9 and 35.2 percent of patients randomly assigned to pelabresib-ruxolitinib and placebo-ruxolitinib, respectively. The absolute change in total symptom score (TSS) was –15.99 and –14.05, respectively; a ≥50 percent decrease from baseline in TSS response at week 24 was achieved in 52.3 and 46.3 percent, respectively, for pelabresib-ruxolitinib and placebo-ruxolitinib. The most common treatment-emergent adverse events were thrombocytopenia (occurring in 52.8 and 37.4 percent, respectively) and anemia (44.8 and 55.1 percent, respectively). "The phase 3 MANIFEST-2 study provides important insights into disease biology and modification, supporting the combination of pelabresib plus ruxolitinib for JAK inhibitor-naive patients with myelofibrosis," the authors write. Several authors disclosed ties to pharmaceutical companies, including Novartis; the MANIFEST-2 study was funded by Constellation Pharmaceuticals, a Novartis Company. Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Phase 3Clinical ResultPhase 2

22 Jan 2025

·www.fiercepharma.com

JPM25: Incyte plans to turn 'a lot of cards' in 2025 as CEO eyes 2 types of deals

For dealmaking purposes, Incyte CEO Hervé Hoppenot said the company is currently only looking for commercial products or early-stage assets with novel technologies. During his presentation at the J.P. Morgan Healthcare Conference last week, Incyte CEO Hervé Hoppenot took investors on a whirlwind tour of 18 events that could take place throughout 2025.“We will be turning a lot of these cards during the year,” Hoppenot said during an interview with Fierce Pharma on the sidelines of JPM.Among the 18 events, Incyte is preparing for four launches across cancer and immunology, and it’s gearing up for four pivotal readouts, including two that investors are watching closely. Overall, Hoppenot said he’s looking forward to an eventful 2025 as Incyte reels from some bad news in its pipeline and as the company remains open to two specific types of deals. Expanding commercial products Together with partner Syndax Pharmaceuticals, Incyte in August won the FDA’s approval for Niktimvo in third-line chronic graft-versus-host disease. Trying to get a smaller vial approved, the partners are aiming to embark on an official rollout soon.Also in immunology, Incyte is trying to build on the successful launch of Opzelura cream, with a proposed pediatric expansion in atopic dermatitis submitted to the FDA and a phase 3 prurigo nodularis readout expected in the first half of 2025.On the oncology side of the business, the firm is counting on two potential FDA nods in the second half of the year—one for CD19 antibody Monjuvi in follicular lymphoma and the other for PD-1 inhibitor Zynyz in first line squamous cell anal carcinoma.Incyte had originally tried to get Zynyz approved in previously treated anal cancer, but its effort was shot down by the FDA in 2021 after a negative review from an advisory committee.This time, Hoppenot argued Zynyz’s data set in the first-line setting is “as clear as it could be,” adding that the company doesn’t anticipate any regulatory hurdles. In a first-in-class win, Zynyz and chemotherapy slashed the risk of progression or death by 37% compared with chemo alone in first-line anal cancer in the phase 3 POD1UM-303 trial.Incyte last year also reported a positive outcome from the POD1UM-304 study, which pitted a Zynyz-chemo combo against solo chemo in first-line non-small cell lung cancer. Given the chemo comparator arm and how PD-1 drugs such as Merck & Co.’s Keytruda have already become the standard of care, the FDA will probably not consider Incyte’s study sufficient to support an approval.Incyte is still speaking with the FDA about the indication, and Hoppenot acknowledged that the agency has “been always asking questions about the relevance of having one more of the same thing.”But the company’s main business plan for the PD-1 latecomer is not necessarily in the U.S. market. Instead of the drug becoming a big contributor to the top line, Hoppenot views Zynyz as an “opportunistic product” for parts of the world where first-line access to PD-1 drugs isn’t established. To seek easy green lights in places such as the Middle East and Brazil, Incyte will first need a reference approval. If not from the FDA, such a nod could come from authorities in the U.K. or Switzerland, Hoppenot explained. This strategy of using a reference approval to move into emerging markets is also being used by many Chinese PD-1 developers. The biggest opportunity that could emerge from Incyte’s oncology department in 2025 is an upcoming phase 3 readout for Monjuvi in first-line diffuse large B-cell lymphoma (DLBCL). While this is a large indication, Incyte is forecasting a U.S. market opportunity below $1 billion, partly because of competition from Roche’s recent entrant, the antibody-drug conjugate Polivy.After Roche’s hard-fought first-line approval for the Polivy-R-CHP combination regimen in 2023, around 20% of new DLBCL patients are starting on the regimen, Hoppenot noted.Meanwhile, Incyte’s phase 3 frontMIND study is testing the addition of Monjuvi to the R-CHOP regimen versus R-CHOP itself. Hoppenot said he’s optimistic about a positive readout given the strong performance of the CD19-CD20 combination approach in follicular lymphoma in the phase 3 inMIND trial. Advancing a ‘full’ portfolio despite setbacks In keeping with the cards theme, Incyte has faced its share of difficult poker hands lately. And the CEO continues to field investor questions about life after Jakafi’s expected loss of exclusivity in the U.S. in 2028.The most disappointing development the company has faced is perhaps a preclinical toxicology discovery from INCB000262, the crown jewel of Incyte’s $750 million buyout of Escient Pharmaceuticals. As a result of the safety signal, clinical development of the MRGPRX2 inhibitor was put on hold in November, less than six months after the acquisition.While Incyte is still trying to elucidate the problem and has not decided whether it needs to turn to a backup molecule, “the probability of moving forward is relatively low,” Hoppenot explained.“You can acquire an asset that is well understood and that will cost you billions, or you acquire an early asset, like what we did, and it will cost you millions instead," Hoppenot said. “There is no way you can predict it, and that’s part of the trade-off,” the CEO added.Another safety cloud forming over Incyte’s pipeline pertains to the BET inhibitor class. Novartis recently postponed potential regulatory filings for its BET inhibitor candidate pelabresib, which was acquired in its $2.9 billion MorphoSys takeout, because of malignant transformations identified during clinical testing.Updated MANIFEST-2 trial data presented in December showed that among myelofibrosis patients who received the combination of Jakafi and pelabresib, 6.1% developed acute myeloid leukemia (AML). The number compared with 4.2% for those who took Jakafi alone.In a phase 1 study, Incyte spotted a rate of AML transformations of 4.9% for its BET inhibitor INCB057643 among patients with high-risk myelodysplastic syndromes or myelofibrosis. Patients with those blood disorders are naturally at risk of developing AML, Hoppenot noted, arguing that it’s too early to conclude there is a classwide problem for BET inhibitors. The only way to know for sure is through a randomized study with a comparator arm.Unlike Novartis’ front-line study, Incyte is launching a phase 3 trial for its BET inhibitor as a monotherapy in the post-Jakafi setting. The company has not decided whether it will run a similar BET-Jakafi combo trial in the first line “because there is a portfolio question for us with two other projects,” Hoppenot said, pointing to the company's early-stage mutant CALR antibody and JAK2V617F inhibitor.Depending on phase 1 readouts for those candidates, Incyte will have the luxury of deciding whether it makes sense to move a BET inhibitor into the first-line setting, the CEO explained.An opportunity in hidradenitis suppurativa Despite questions around the BET class and the Escient buy, Hoppenot argued Incyte’s portfolio is currently “full.” Investors are also waiting with bated breadth to see phase 3 results for povorcitinib in hidradenitis suppurativa (HS) in the first quarter of 2025.HS represents a historically underserved population. For years, AbbVie’s Humira served as the only treatment option until the recent approvals of Novartis’ Cosentyx and UCB’s Bimzelx, Leerink Partners analysts said in a recent note.Studies suggest the disease affects about 4% of the population, according to Leerink. If successful, Incyte's povorcitinib could become the first oral drug for the indication. HS could represent a $10 billion annual market opportunity that's “capable of supporting multiple blockbuster agents,” according to the Leerink analysts. “We know in dermatology, there are a lot of patients who would rather be treated with the pills than with an injection,” Hoppenot noted, pointing to how Amgen’s Otezla has been successful in psoriasis even though it’s considered less efficacious than biologics.What Incyte is gunning for is biologiclike efficacy in an oral drug, Hoppenot said of povorcitinib.The chief executive didn’t directly answer a question about whether Incyte would need to turn to M&A if povorcitinib were to fail in HS. For now, with a “full” portfolio, Incyte is only considering two types of deals, according to Hoppenot.“If we look for something, it would be mostly new technologies that we don’t have. So, early-stage, exotic stuff,” Hoppenot said, “or on the opposite end, commercial product, because that will be contributing to the top line immediately.”The company will also stick to its interest areas, namely cancer and dermatology, he said.

Phase 3Clinical ResultDrug ApprovalPhase 1Acquisition

100 Deals associated with Pelabresib

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Leukemia	Phase 3	United States	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Leukemia	Phase 3	Belgium	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Leukemia	Phase 3	Italy	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Leukemia	Phase 3	Netherlands	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Leukemia	Phase 3	United Kingdom	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Solid tumor	Phase 3	United States	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Solid tumor	Phase 3	Belgium	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Solid tumor	Phase 3	Italy	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Solid tumor	Phase 3	Netherlands	Constellation Pharmaceuticals, Inc.	13 Aug 2024
Solid tumor	Phase 3	United Kingdom	Constellation Pharmaceuticals, Inc.	13 Aug 2024

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04603495 (MANIFEST-2, Pubmed \| Nat Med)	Phase 3	Myelofibrosis First line	-	Pelabresib 125 mg QD + Ruxolitinib 10 or 15 mg BID	gptqelwdjy(xnrhcycige) = cgwvjreene kjbkhvzthx (kzghtoaysq ) View more	Positive	10 Mar 2025
				Placebo + Ruxolitinib 10 or 15 mg BID	gptqelwdjy(xnrhcycige) = yhiygrczip kjbkhvzthx (kzghtoaysq ) View more
NCT04603495 (MANIFEST-2, CTgov)	Phase 3	Post-essential thrombocythemia myelofibrosis \| Post-polycythemia vera myelofibrosis \| Primary Myelofibrosis	430	Ruxolitinib+Pelabresib (Pelabresib + Ruxolitinib)	jfxdrvavtk = plskkkvbuz izxrhpuvjp (xfrowcgqpp, giorlaefho - iakgkqajwa) View more	-	28 Oct 2024
				Placebo+Ruxolitinib (Placebo + Ruxolitinib)	jfxdrvavtk = putevzllmr izxrhpuvjp (xfrowcgqpp, luaramnomg - tvphzzoptv) View more
SOHO2024	Not Applicable	Myelofibrosis	-	Pelabresib+ruxolitinib	mjteqjvupo(nnoanmdizl) = 43.9% vs 54.7% jblxiykutn (lxtxluzfyn ) View more	-	04 Sep 2024
				Placebo+ruxolitinib
NCT04603495 (MANIFEST-2, ASCO2024) Manual	Phase 3	Myelofibrosis	430	Pelabresib + Ruxolitinib	bcqwmpbqyn(qrhjxvhwia) = xuzcafrrxf zlwhzsbrti (yptmwodjyj ) View more	Positive	24 May 2024
				Placebo + Ruxolitinib	bcqwmpbqyn(qrhjxvhwia) = zvccyxfqnf zlwhzsbrti (yptmwodjyj ) View more
NCT04603495 (MANIFEST-2, EHA2024) Manual	Phase 3	Myelofibrosis JAK2	-	Pelabresib+Ruxolitinib	wmwphruijd(framtewgbg) = ddzwcjlxjl ptotergulg (aafgjlqbep, -36.5 to -31.1) View more	Positive	14 May 2024
				Placebo+Ruxolitinib	wmwphruijd(framtewgbg) = uocquwphmq ptotergulg (aafgjlqbep, -23.7 to -17.9) View more
NCT02158858 (MANIFEST, Pubmed) Manual	Phase 1	Myeloid Tumor Protein Expression Markers	44	Pelabresib	vvtbjlrzhs(mwbwtqepfu) = nausea, decreased appetite, and fatigue cswjanvuev (zxedlmarbq ) View more	Positive	23 Jan 2024
				Pelabresib (acute leukemia)
NCT04603495 (MANIFEST-2, Corporate Publications) Manual	Phase 3	Primary Myelofibrosis	430	Pelabresib + Ruxolitinib	ntagfjvysc(gjcqwukrmf) = ayvwzdquub jhrccjeqgs (egnxidhxgg ) Met View more	Positive	20 Nov 2023
				Placebo + Ruxolitinib	ntagfjvysc(gjcqwukrmf) = koutdldkxo jhrccjeqgs (egnxidhxgg ) Met View more
NCT02158858 (MANIFEST, EHA2023)	Phase 2	Acute Myeloid Leukemia \| Thrombocytopenia \| Hematologic Neoplasms ... View more	84	PELA + RUX	aaswhralbe(wrbrjjkdxj) = pghyhkzmzy bxaxklvojp (mctfwxmljg ) View more	-	08 Jun 2023
NCT02158858 (MANIFEST, EHA2023)	Phase 2	Primary Myelofibrosis Add-on	87	PELA + RUX	rpofcivyuw(fxrkupmeyw) = jmdkbhrkhj pksblazlrw (nexycptfkv ) View more	-	08 Jun 2023
NCT02158858 (ASCO 12023 \| ASCO 22023) Manual	Phase 1/2	Thrombocythemia, Essential	20	Pelabresib 225mg	pfjjabajwn(gyygjnosii) = lxzxnktkjt hqajmvxjfy (rrbphtushz ) View more	Positive	31 May 2023

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