Pelabresib

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.

Longer-term 96-week results from Scemblix® ASC4FIRST Phase III study in first-line Ph+ CML-CP to be presented following recent FDA approval based on 48-week data Late-breaking Kisqali®* 4-year analysis on distant disease-free survival in key subgroups with HR+/HER2- early breast cancer from Phase III NATALEE trial also to be presentedPipeline updates demonstrate advancement in research and development programs in hematologic diseases and cancers Basel, November 25, 2024 – Novartis will present data from more than 65 abstracts, including investigator-initiated trials at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition and the 2024 San Antonio Breast Cancer Symposium® (SABCS). “By prioritizing research in areas of greatest medical need and focusing on earlier stages of disease, we aim to change the treatment paradigm for people who require additional treatment options,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. “The new data being presented at ASH and SABCS underscore our commitment to patients with cancer or blood disorders and follow new, expanded indications for Scemblix and Kisqali along with recent updates in national treatment guidelines." In addition to late-breaking data, Novartis will host an art gallery-style exhibit at SABCS featuring personal letters and stories written by people impacted by breast cancer, sharing their raw, authentic perspectives on aspects of the breast cancer journey. These letters and stories aim to uplift patients, encourage reflection, and demonstrate strength and unity among the breast cancer community. Key abstracts accepted by ASH include: Medicine or Disease State      Abstract Title      Abstract Number/ Presentation Details       Scemblix®Asciminib (ASC) Demonstrates Favorable Safety and Tolerability Compared with Each Investigator-Selected Tyrosine Kinase Inhibitor (IS TKI) in Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) in the Pivotal Phase 3 ASC4FIRST Study Abstract #475Oral PresentationSunday, December 89:30 – 11:00 AM PTScemblix   Efficacy and Safety of Asciminib in Chronic Myeloid Leukemia in Chronic Phase (CML-CP): Interim Results from the Phase 2 ASC2ESCALATE Trial in the Cohort of Patients (Pts) after 1 Prior Tyrosine Kinase Inhibitor (TKI) Abstract #479Oral PresentationSunday, December 89:30 – 11:00 AM PTScemblix Asciminib Shows High Efficacy and Favorable Tolerability at 80 Mg Once Daily and 40 Mg Twice Daily in Patients with Chronic Phase Chronic Myelogenous Leukemia Previously Treated with 2 or More Tyrosine Kinase Inhibitors: Primary Analysis from the ASC4OPT Study Abstract #4526Poster PresentationMonday, December 96:00 – 8:00 PM PTScemblix Treatment with Asciminib as a Second Line after One Prior Tyrosine Kinase Inhibitor (TKI) in Patients with Chronic-Phase Chronic Myeloid Leukemia (CML-CP)– a Chart Review Study in the United States Abstract #3812Poster PresentationSunday, December 86:00 – 8:00 PM PTIanalumab (VAY736)A Phase 2 Study of Ianalumab in Patients with Primary Immune Thrombocytopenia Previously Treated with at Least Two Lines of Therapy: Interim Results from VAYHIT3 Abstract #710Oral PresentationMonday, December 910:30 AM – 12:00 PM PTRapcabtagene autoleucel (YTB323)Rapcabtagene Autoleucel (YTB323) in Patients (Pts) with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): Phase II Trial Clinical Update Abstract #67Oral PresentationSaturday, December 79:30 – 11:00 AM PTFabhalta®Oral Iptacopan Monotherapy Leads to Long-Term Improvements in Patient (Pt)-Reported Health-Related Quality of Life (HRQoL) and Investigator-Assessed Signs and Symptoms of Paroxysmal Nocturnal Hemoglobinuria (PNH): 48-Week (Wk) Results from the Phase III APPLY-PNH and APPOINT-PNH Trials Abstract #4079Poster PresentationMonday, December 96:00 – 8:00 PM PTFabhalta The Effect of Oral Iptacopan Monotherapy on Hematological Parameters in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Is Consistent Regardless of the Type of Prior Anti-C5 Treatment Received: A Post Hoc Analysis of 24-Week Data from the Randomized Phase III APPLY-PNH Trial Abstract #4087Poster PresentationMonday, December 96:00 – 8:00 PM PTFabhalta Baseline Characteristics of Individuals with Paroxysmal Nocturnal Hemoglobinuria in an App-Based Home-Reported Outcomes Study to Evaluate Disease Burden Abstract #2327Poster PresentationSaturday, December 75:30 – 7:30 PM PTPelabresib (CPI-0610)Updated Results from the Phase 3 Manifest-2 Study of Pelabresib in Combination with Ruxolitinib for Janus Kinase Inhibitor–Naïve Patients with MyelofibrosisAbstract #3178Poster PresentationSunday, December 86:00 PM - 8:00 PM PT Key abstracts accepted by SABCS include: Medicine or Disease State      Abstract Title      Abstract Number/ Presentation Details       Kisqali® (ribociclib)* Distant disease-free survival (DDFS) across key subgroups from the phase 3 NATALEE trial of ribociclib (RIB) plus a nonsteroidal aromatase inhibitor (NSAI) in patients with HR+/HER2- early breast cancer (EBC) Abstract #P4-09-22Poster SessionThursday, December 125:30 – 7:30 PM CST Kisqali     Impact of ribociclib dose reduction on efficacy in patients with hormone receptor– positive/human epidermal growth factor receptor 2–negative (HR+/HER2-) early breast cancer (EBC) in NATALEE Abstract #P1-11-16Poster Session Wednesday, December 1112:30 – 2:00 PM CSTKisqali Risk of recurrence in real-world (RW) NATALEE- and monarchE-eligible populations of patients with HR+/HER2- early breast cancer (EBC) in an electronic health record (EHR)-derived database Abstract #P2-12-02Poster SessionWednesday, December 115:30 – 7:00 PM CST Kisqali Tolerability of First-Line (1L) Treatment (tx) With Ribociclib (RIB) for Metastatic Breast Cancer (MBC) Using 2 Large US Data Sources Abstract #P3-10-14Poster SessionThursday, December 1212:30 – 2:00 PM CST Kisqali Impact of body mass index (BMI) on the safety and efficacy of ribociclib (RIB) in patients (pts) with HR+/HER2- advanced breast cancer (ABC): pooled analysis of the MONALEESA (ML)-2, -3, and -7 trials Abstract #P2-09-20Poster SessionWednesday, December 115:30 – 7:00 PM CST Kisqali First-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in clinically aggressive HR+/HER2- advanced breast cancer (ABC): a subgroup analysis of RIGHT Choice by intrinsic subtype & gene & signature expression Abstract #PS2-06Poster PresentationThursday, December 127:00 – 8:30 AM CST Product Information     For full prescribing information, including approved indications and important safety information about marketed products, please visit https://www.novartis.com/about/products. 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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 more than 250 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. 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