Blast Phase Chronic Granulocytic Leukemia

Five years after shelling out more than $5 billion for Ariad Pharmaceuticals and its rare leukemia drug Iclusig, Takeda is setting plans in motion for a potential label expansion into the first-line setting — but for now, the pharma giant is keeping its cards close. Iclusig and reduced intensity chemotherapy successfully beat out Novartis’ Gleevec in treating newly diagnosed patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in the Phase III PhALLCON trial, Takeda announced on Thursday. While researchers haven’t released any hard data, they did say that the open-label study met its primary endpoint by achieving higher rates of minimal residual disease (MRD)-negative complete remission (CR) compared to Gleevec. “It’s a large magnitude,” Awny Farajallah, Takeda’s global head of medical affairs for oncology, said in an interview. While declining to get into specifics, he added that more information is coming soon. If approved, Iclusig would be the first TKI available for patients in this front-line setting. “We are currently in the process of discussing with regulators on how we’re going to approach that, so the time frame is, it’s going to be very soon,” Farajallah said. Takeda’s stock $TAK was up about 1% on Thursday afternoon, pricing at around $13.92 per share. Iclusig won an accelerated approval back in 2012 to treat certain patients with Ph+ ALL and chronic, accelerated or blast phase chronic myeloid leukemia (CML) who have failed on or are intolerant to prior TKI therapy. A year later, the drug was briefly suspended over blood clot concerns, leading the FDA to require new safety warnings including a description of “arterial and venous thrombosis and occlusions that have occurred in at least 27% — more than one in every four — of patients treated with Iclusig,” the agency said at the time. A full approval came in 2016 based on two-year follow-up data, and Farajallah said those risks have been “extensively studied” and characterized on the drug’s label, adding that “we don’t see any further concerns with it as we move forward.” No new safety signals were identified in the PhALLCON trial, he said. In 2017, Takeda inked a deal to take over Ariad, Iclusig and the ALK-inhibiting lung cancer drug Alunbrig, and last year, Iclusig raked in ¥34.2 billion, or nearly $244 million. While Iclusig faces stiff competition from rivals such as Pfizer’s Bosulif and Novartis’ Scemblix, both approved in Ph+ CML, Farajallah stressed that a front-line win would add a “very unique indication” to the label. “There are currently no targeted therapies, as we’ve mentioned, that can be used in that first line and I think that is why we are excited about this,” he said.

SUZHOU, China, and ROCKVILLE, Md., Nov. 3, 2022 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, today announced that the updated results from three studies of the company's novel drug candidate, olverembatinib (HQP1351), have been selected for oral presentations at the 64th American Society of Hematology (ASH) Annual Meeting. This is the fifth consecutive year in which studies of olverembatinib were selected for oral presentations at the ASH Annual Meeting, a growing recognition of the drug candidate's promising efficacy and safety by the international hematology community. It is worth noting that in this year, five studies of Ascentage Pharma's three drug candidates (olverembatinib, lisaftoclax, alrizomadlin), have been selected for presentations, including four oral presentations. It is worth noting that these results selected for oral presentations at the ASH Annual Meeting also include the first batch of safety and efficacy data from the first US study of olverembatinib in patients with chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). These interim results suggest that olverembatinib has promising efficacy and is well tolerated in patients with drug-resistant CML and Ph+ ALL, and has shown promising efficacy in patients who were ponatinib or asciminib resistant. Overall, these interim results signal olverembatinib's potential as the world's first next-generation BCR-ABL inhibitor that could overcome resistance to ponatinib or asciminib. Additionally, data selected for the other two oral presentations include the updated results from a Phase II pivotal study of olverembatinib in patients with tyrosine kinase inhibitor (TKI)-resistant CML harboring the T315 mutation and the five-year follow-up data from a Phase I study in Chinese patients with TKI-resistant CML. These results further validate the promising safety and efficacy of olverembatinib. The ASH Annual Meeting is one of the largest gatherings of the international hematology field, bringing together the latest and most cutting-edge scientific and clinical research in hematology. The 64th ASH Annual Meeting will take place on December 11-14, 2022, both online and in-person in New Orleans, the United States. Developed by Ascentage Pharma, olverembatinib is a potential best-in-class novel drug that has been designated a Major New Drug Project by China's Ministry of Science and Technology. As the first approved third-generation BCR-ABL inhibitor in China and the second in any country globally, olverembatinib is recommended by both the Guidelines of the Chinese Society of Clinical Oncology (CSCO) and the China Anti-Cancer Association's (CACA) Guidelines for the Holistic Integrative Management of Cancers, for the treatment of patients with TKI-resistant CML harboring the T315I mutation (while the CACA Guidelines also recommend olverembatinib for the treatment of patients with CML intolerant/resistant to at least two TKIs). Globally, despite the clinical adoption of other TKI, patients with CML still have enormous unmet medical needs due to the limited accessibility as well as adverse events, resulting in the strong interest in the clinical progress with olverembatinib from the global hematology community in recent years. At present, olverembatinib is being evaluated in a Phase Ib study in the US for the treatment of drug-resistant CML. Furthermore, olverembatinib has been granted one Fast Track designation and three Orphan Drug designations by the US Food and Drug Administration (FDA), and one Orphan Drug designation by the European Medicines Agency (EMA). To address the unmet medical needs in patients with CML, Ascentage Pharma is pressing ahead with the global clinical development of olverembatinib and advancing the drug towards approvals in more countries. Driven by a sense of urgency to facilitate the early access by patients with malignancies that currently lack treatment options, Ascentage Pharma and Tanner Pharma Group, a global pharmaceutical services provider of specialty access solutions, jointly launched an innovative Named Patient Program (NPP) for olverembatinib in July 2022. This collaboration will allow access to olverembatinib on a named patient basis in over 140 countries and regions where the drug is not yet commercially accessible, in a manner that is reliable, responsible, ethical and in accordance with all country-specific regulatory requirements. "For five consecutive years, results of olverembatinib have been selected for oral presentations at the ASH Annual Meeting, thus setting a new record signifying the growing recognition from the international hematology community," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "The first US data of olverembatinib showed the drug's potential as the world's first BCR-ABL inhibitor that can overcome the resistance to ponatinib and asciminib. We are encouraged by these results because they further validate that olverembatinib can potentially bring a long-awaited change to the treatment landscape in CML by effectively addressing the unmet needs of patients with CML globally. Moving forward, we will continue to accelerate the global clinical development of olverembatinib to fast track the drug towards approvals in overseas markets and more indications in China, with the hope of benefiting more patients around the world." "We have also launched a Global Named Patient Program in 140 countries where the drug is not commercially available. The program makes Olverembatinib available to patients at the treating physician's decision in these countries", said Prof Dajun Yang, Chairman and CEO of Ascentage Pharma. The three abstracts of olverembatinib to be reported in oral presentations at this year's ASH Annual Meeting are as follows (for details of the oral presentation on lisaftoclax, please refer to a parallel press release): Olverembatinib (HQP1351) Overcomes Ponatinib Resistance in Patients with Heavily Pretreated/Refractory Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Format: Oral Presentation Abstract: 162387 Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Novel Agents Time: Saturday, December 10, 2022, 10:15 AM, Eastern Time / Saturday, December 10, 2022, 11:15 PM, Beijing Time Highlights: Olverembatinib is a novel third-generation BCR-ABL1 TKI with antitumor activity against CML and Ph+ ALL and a favorable safety profile. This multicenter, open-label, randomized trial is the first to report on the safety, efficacy, and pharmacokinetics (PK) of olverembatinib in patients with CML and Ph+ ALL outside China, who were intolerant or resistant to at least 2 BCR-ABL1 inhibitors, including ponatinib and asciminib, except for those whose disease harbors the T315I mutation, for whom the number of prior lines of therapy is not limited. Study participants were randomized in a ratio of 3:3:2 to receive olverembatinib 30, 40, or 50 mg QOD in 28-day cycles. A total of 30 patients have been enrolled, including 23 with CML-CP, 4 with CML-AP, 2 with blast-phase CML (CML-BP), and 1 with Ph+ ALL. The median treatment duration was 4.8 (range, 0.03-21.29) months and the median interval from CML/Ph+ ALL diagnosis to receiving the olverembatinib treatment was 7.0 (range, 1.5-24.0) years. Half (15/30) of patients were men, and the median age was 47.0 (range, 21.0-74.0). In all, 1 (3.3%), 7 (23.3%), 8 (26.7%), and 9 (30.0%) patients received 2, 3, 4, and ≥ 5 prior TKIs, respectively. A total of 21 (70.0%) patients were pretreated with the third-generation TKI ponatinib, including 17 (81.0%) with resistance and 4 (19.0%) with intolerance; a total of 5 (16.7%) were pretreated with asciminib; 12 (40.0%) had T315I mutations; and 13 (43.3%) had hypertension. Safety: Olverembatinib was well tolerated. 22 (73.3%) patients experienced treatment related adverse events (TRAEs) of any grade, the incidence of which tended to be dose-dependent. Most of the nonhematologic TRAEs were grade 1/2. Common grade 3/4 nonhematologic TRAEs included thrombocytopenia (7/30; 23.3%), neutropenia (5/30; 16.7%), and decreased leukocyte counts (4/30; 13.3%). Of all 30 patients, 11(36.7%) experienced serious adverse events (SAEs), of which 6 (20%) were considered olverembatinib-related and 1 (3.3%) led to treatment discontinuation. 1 patient with CML-AP from the 50 mg dose cohort died of progressive disease (PD). Preliminary efficacy: Olverembatinib conferred potent antileukemic activity in patients with CML and Ph+ ALL. Of 21 efficacy-evaluable patients, 17 were evaluable for cytogenetic response, of whom 10 (58.8%) had a complete cytogenetic response (CCyR); 9/21 (42.9%) patients had a major molecular response (MMR). Olverembatinib was effective in patients with either the T315I-mutant (62.5%, CCyR; 50%, MMR) or T315I un-mutant (55.6%, CCyR; 38.5%, MMR), and its effectiveness was not compromised by prior use of ponatinib or asciminib. Among patients with ponatinib-resistant disease, 5/9 (55.6%) experienced CCyR and 6/11 (54.5%) experienced MMR. 4 of 5 patients pretreated with asciminib showed response. PK analysis indicated a dose-proportional increase in olverembatinib plasma exposure from 30 to 50 mg QOD and comparable plasma exposures between Chinese and US CML populations. Conclusions: Olverembatinib monotherapy is efficacious and well tolerated in patients with TKI-refractory CML and Ph+ ALL. Even in patients with CML who were ponatinib or asciminib resistant, or who had T315I mutations, olverembatinib also showed strong efficacy. Updated Results of Pivotal Phase 2 Trials of Olverembatinib ( HQP1351) in Patients ( Pts) with Tyrosine Kinase Inhibitor ( TKI) -Resistant Chronic- and Accelerated-Phase Chronic Myeloid Leukemia ( CML-CP and CML-AP) with T315I Mutation Format: Oral Presentation Abstract: 170698 Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Novel Agents Time: Saturday, December 10, 2022, 10:30 AM, Eastern Time / Saturday, December 10, 2022, 11:30 PM, Beijing Time Highlights: The T315I mutation can confer a high degree of resistance to many first- and second-generation TKIs. Olverembatinib is a novel, orally active, third-generation BCR-ABL1 TKI. These Phase II pivotal trials, HQP1351-CC-201 and HQP1351-CC-202, conducted based on favorable Phase I trial results, showed that olverembatinib was efficacious and well tolerated in patients with TKI-resistant CML-CP and CML-AP with the BCR-ABL1T315I mutation. The HQP1351-CC-201 Study (in patients with CML-CP) As of the cutoff date of April 30, 2022, 41 patients were enrolled, of whom 21 (51.2%) were male, with a median age of 47 (range, 22-70) years. The median interval from CML diagnosis to first olverembatinib dose was 5.31 (range, 0.6-23.2) years, and 32 (78.1%) patients had received ≥ 2 prior TKIs. The median treatment duration was 32.7 (range, 3.1-36.7) months. Preliminary efficacy: 100% of patients achieved complete hematologic response (CHR) (31/31, 10 others had CHR at baseline), 34/41 (82.9%) had a major cytogenetic response (MCyR), 29/41 (70.7%) CCyR, and 24/41 (58.5%) MMR. Median time to CHR was 1 (95% CI: 1.0-1.9) month, median time to MCyR was 2.8 (95% CI: 2.8-5.6) months, and median time to MMR was 6.5 (95% CI: 2.8 to not reached [NR]) months. At 36 months, the progression-free survival (PFS) rate was 86.3% (95% CI: 70.2%-94.1%) and the overall survival (OS) rate was 95.1% (95% CI: 81.9%-98.8%). A total of 5 patients withdrew because of PD, 4 intolerances, 3 consent withdrawals, and 2 for other reasons. Safety: Frequent TRAEs (all grades; grade 3-4; SAEs) included thrombocytopenia (70.7%; 48.8%; 7.3%), anemia (70.7%; 31.7%; 2.4%), leukopenia (51.2%; 14.6%; 0), and neutropenia (41.4%; 21.9%; 0). Common nonhematologic TRAEs (all grades; grade 3-4) included skin pigmentation (56.1%; 0%) and elevations in creatine kinase (56.1%; 19.5%), alanine transaminase (ALT, 43.9%; 2.4%) and aspartate aminotransferase (AST, 36.6%; 0) levels. The HQP-1351-CC-202 Study (in patients with CML-AP) As of the cutoff date of April 30,2022, 23 patients were enrolled, of whom 18 (78.3%) were male, with a median age of 41 (range, 21-74) years. The median interval from CML diagnosis to first olverembatinib dose was 4.96 (range, 0.4-10.2) years, and 19 (82.6%) patients had received ≥ 2 prior TKIs. The median treatment duration was 19.7 (range, 1.4-36.4) months. Preliminary efficacy: A total of 18 (78.3%) patients experienced a major hematologic response (MaHR) (73.9% CHR and 4.4% no evidence of leukemia [NEL]); 12 (52.2%) MCyR; 12 (52.2%) CCyR; and 11 (47.8%) MMR. The median time to MaHR was 2.8 (95% CI: 1.0-4.7) months, the median time to MCyR was 5.6 (95% CI: 2.00-NR) months, and the median time to MMR was 13.1 (95% CI: 5.6-22.4) months. At 36 months, the PFS rate was 57.1% (95% CI: 33.3%-75.1%) and the OS rate was 69.6% (95% CI: 46.6%-84.2%). 6 patients withdrew because of PD, 4 because of intolerances, and 1 for other reasons; two patients died. Safety: Common TRAEs (all grades; grade 3-4; SAEs) included thrombocytopenia (78.3%; 56.5%; 17.4%), anemia (69.6%; 34.8%; 13.0%), leukopenia (56.5%; 30.4%; 0), and neutropenia (26.1%; 26.1%; 0). Common nonhematologic AEs included skin pigmentation (69.6%), hypocalcemia (52.2%), proteinuria (56.5%), hypertriglyceridemia (60.9%), hyperphosphatemia (47.8%), hyperuricemia (26.1%), and arthralgia (34.8%), of which most were grade 1-2. Conclusions: Olverembatinib was efficacious and well tolerated in patients with TKI-resistant CML-CP and CML-AP with the BCR-ABL1T315I mutation. Based on the results of these pivotal trials, the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) granted conditional approval for olverembatinib in November 2021. A Five-Year Follow-up on Safety and Efficacy of Olverembatinib ( HQP1351) , a Novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI) , in Patients with TKI-Resistant Chronic Myeloid Leukemia (CML) in China Format: Oral Presentation Abstract: 170868 Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Novel Agents Time: Saturday, December 10, 2022, 10:00 AM, Eastern Time / Saturday, December 10, 2022, 11:00 PM, Beijing Time Highlights This open-label, multi-center Phase I study assessed a 5-year follow-up on the safety and efficacy of olverembatinib in adult patients with CML-CP or CML-AP resistant or intolerant to first- or second-generation TKIs. Patients evaluated in the study were orally administered olverembatinib QOD in 28-day cycles in 11 dose cohorts ranging from 1 to 60 mg. From October 26, 2016, to April 30, 2022 (data cutoff date), 101 patients with CML-CP (n = 86) and CML-AP (n = 15) were enrolled and treated with olverembatinib. The median treatment duration was 44.7 (1.2-63.1) months. 71 (70.3%) patients were male, with a median age of 40 (range, 20-64) years and a median interval from diagnosis to initial olverembatinib treatment of 6.0 (range, 0.3-15.2) years. A total of 84 (83.2%) patients received ≥2 lines of TKI therapy, and 63 (62.4%) had disease harboring the T315I mutation. At baseline, compound mutations were detected in 12 (11.9%) patients, of whom 8 (66.7%) harbored the BCR-ABL1T315I mutation. A total of 20 (19.9%) patients had 2 (n = 13) or ≥ 3 (n = 7) mutations. As of the data cutoff date, 72 (71.3%) patients continued treatment and 28 (21 with CML-CP and 7 with CML-AP) discontinued because of disease progression, intolerance, or other reasons. The cumulative median drug exposure dose was 20,175 (range, 660-34,395) mg. Of the 101 patients, 79 (78.2%) were treated > 3 years, 21 (20.8%) > 4 years, and 3 (3.0%) > 5 years. Preliminary efficacy: Of the evaluable patients with CML-CP, 100% experienced CHR, 80% MCyR, 71.3% CCyR, and 55.3% MMR; Of the evaluable patients with CML-AP, 85.7% had CHR and 40% each for MCyR, CCyR, and MMR; Of evaluable patients with the T315I mutation, 100% of those with CML-CP experienced CHR, 83.7% MCyR, and 73.1% MMR and 80.0% with CML-AP had CHR and 54.5% each for MCyR and MMR. PFS at 48 months was 85.6% (95% CI: 70.6%-93.3%) in patients with CML-CP and 50.0% (95% CI: 22.9%-72.2%) in patients with CML-AP; In the 12 patients with compound mutations, next-generation sequencing confirmed that 7 (58.0%) experienced MMR and 3 (25.0%) MR4.5. At the last follow-up, 3 patients had progressed to CML-AP or CML-BP and died, and 7 remained on olverembatinib. One patient had an MMR and 2 each CHR, CCyR, or MR4.5. Safety: Most TRAEs were grade 1-2. The most frequent nonhematologic AE was, primarily, grade 1-2 skin hyperpigmentation (85.1%). Grade ≥ 3 nonhematologic AEs included hypertriglyceridemia (10.9%), pyrexia (6.9%), and proteinuria (6.9%). The common hematologic TRAE was thrombocytopenia, which was observed in 79 (78.2%) patients, including 52 (51.5% of total population) with grade ≥ 3 and 7 (6.9%) with SAEs. Leukopenia was grade ≥ 3 in 21 (20.8%) patients but not serious, while anemia was grade ≥ 3 in 17 (16.8%) and serious in 4 (4.0%). Conclusions: The 5-year follow-up results of this first-in-human trial show durable responses and good tolerance of olverembatinib in heavily pretreated patients with CML. About Ascentage Pharma Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of nine clinical drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 50 Phase I/II clinical trials in the US, Australia, Europe, and China. Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML), was granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) and is already approved for the indication. In addition, olverembatinib was also granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EU. To date, Ascentage Pharma has obtained a total of 15 ODDs, 2 FTDs, and 2 Rare Pediatric Disease (RPD) designations from the FDA and 1 ODD from the EU for four of the company's investigational drug candidates. Ascentage Pharma has been designated for multiple Major National R&D Projects, including 5 National Major New Drug Discovery and Manufacturing projects, 1 New Drug Incubator status, 4 Innovative Drug Programs, and 1 Major Project for the Prevention and Treatment of Infectious Diseases. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, Merck, AstraZeneca, and Pfizer. The company has built a talented team with global experience in discovering, developing, launching, and commercializing innovative drugs and is setting up world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. SOURCE Ascentage Pharma

– This marks the second indication for Pemazyre, which received accelerated FDA approval in 2020 for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement – Pemazyre is the only FGFR inhibitor with multiple indications WILMINGTON, Del.--(BUSINESS WIRE)-- Incyte Corporation (Nasdaq:INCY) today announced that the U.S. Food and Drug Administration (FDA) has approved Pemazyre® (pemigatinib), a selective fibroblast growth factor receptor (FGFR) inhibitor, for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. MLNs with FGFR1 rearrangement are extremely rare and aggressive blood cancers that may impact less than 1 in 100,000 people in the United States1. “The approval of Pemazyre represents an important treatment advancement for people living with MLNs with FGFR1 rearrangement who currently have limited treatment options,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “These are complex hematologic malignancies with a range of presentations, and this approval highlights Incyte’s continued leadership and commitment to advancing care for patients with rare blood cancers.” A patient with an MLN with FGFR1 rearrangement may present with bone marrow involvement with a chronic myeloid malignancy (such as myeloproliferative neoplasm [MPN], myelodysplastic syndrome/MPN) or a blast phase malignancy (such as B- or T-cell acute lymphoblastic leukemia/lymphoma, acute myeloid leukemia or mixed phenotype acute leukemia). Bone marrow involvement may or may not be accompanied by extramedullary disease (EMD); some patients may present with EMD only. MLNs with FGFR1 rearrangement are caused by chromosomal translocations involving the FGFR1 gene, with various partner genes resulting in constitutive activation of the FGFR1 receptor tyrosine kinase, impacting cell differentiation, proliferation and survival2. Patients often relapse because existing first-line therapies sometimes fail to induce durable clinical and cytogenetic responses. The FDA approval was based on data from the Phase 2 FIGHT-203 study, a multicenter open-label, single-arm trial that evaluated the safety and efficacy of Pemazyre in 28 patients with relapsed or refractory MLNs with FGFR1 rearrangement. Patients could have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or after a disease modifying therapy or were not a candidate for allo-HSCT or other disease modifying therapies. Study participants included patients with documented MLNs with an 8p11 translocation on conventional cytogenetics and/or an FGFR1 rearrangement on break-apart FISH testing. (An FDA-approved test for detection of FGFR1 rearrangement in patients with relapsed or refractory MLNs is not available.) In patients with chronic phase in the marrow with or without EMD (N = 18), the complete response (CR) rate was 78% (14/18; 95% CI 52, 94). The median time to response of CR was 104 days (range, 44 to 435 days). The median duration of CR was not reached (range, 1+ to 988+ days). In patients with blast phase in the marrow with or without EMD (N = 4), two patients achieved a CR (duration: 1+ and 94 days). In patients with EMD only (N = 3), one patient achieved a CR (duration: 64+ days). For all patients (N = 28 including three patients without evidence of morphologic disease) the complete cytogenetic response rate was 79% (22/28; 95% CI: 59, 92). The most common (≥ 20%) adverse reactions were hyperphosphatemia (74%), nail toxicity (62%), alopecia (59%), stomatitis (53%), diarrhea (50%), dry eye (50%), fatigue (44%), rash (35%), abdominal pain (35%), anemia (35%), constipation (32%), dry mouth (32%), epistaxis (29%), retinal pigment epithelial detachment (26%), extremity pain (26%), decreased appetite (24%), dry skin (24%), dyspepsia (24%), back pain (24%), nausea (21%), blurred vision (21%), peripheral edema (21%) and dizziness (21%). “In patients with relapsed or refractory MLNs with FGFR1 rearrangement treated with Pemazyre in FIGHT-203, the high rate of complete response and complete cytogenetic response in patients with chronic phase disease and the high rate of complete cytogenetic response in patients with blast phase disease is clinically meaningful, especially in light of the lack of these specific responses with existing first-line treatments,” said Dr. Srdan Verstovsek, M.D., Ph.D., Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, and principal investigator for the FIGHT-203 study. The supplemental New Drug Application (sNDA) for Pemazyre for the treatment of adults with relapsed or refractory MLNs with FGFR1 rearrangement was reviewed by the FDA under Priority Review. The FDA grants Priority Review to medicines that may offer a major advance in treatment where none currently exists. The designation shortens the review period to six months compared to 10 months for Standard Review. Incyte established its leadership in rare blood cancers more than 10 years ago with the development of the first JAK inhibitor approved by the FDA for the treatment of certain patients with myelofibrosis and polycythemia vera. Incyte continues to research additional pathways to address rare blood cancers through its LIMBER (Leadership In MPNs Beyond Ruxolitinib) clinical development program, designed to evaluate multiple therapies and investigational strategies to improve and expand treatments for patients living with MPNs and other related hematologic malignancies and conditions. Incyte is committed to supporting patients and removing barriers to access medicines. Eligible patients in the U.S. who are prescribed Pemazyre have access to IncyteCARES (Connecting to Access, Reimbursement, Education and Support), a comprehensive program offering personalized patient support, including financial assistance and ongoing education and additional resources. More information about IncyteCARES is available by visiting or calling 1-855-452-5234. About FIGHT-203 FIGHT-203 is a Phase 2, multicenter trial that enrolled patients 18 years and older with myeloid/lymphoid neoplasms (MLNs) with a fibroblast growth factor receptor 1 (FGFR1) rearrangement. Sponsored by Incyte, the study evaluated the safety and efficacy of pemigatinib for the treatment of adults with MLNs with FGFR1 rearrangement. Patients received pemigatinib 13.5 mg once daily in 21-day cycles, either on a continuous schedule (the approved recommended starting dosage for use in patients with MLNs with FGFR1 rearrangement) or as an intermittent schedule (14 days on, 7 days off, an unapproved dosage regimen in MLN with FGFR1 rearrangement). Pemigatinib was administered until disease progression or unacceptable toxicity or until patients were able to receive allo-HSCT. For more information about the study, please visit . About Pemazyre® (pemigatinib) Pemazyre, a fibroblast growth factor receptor (FGFR) inhibitor, is the first targeted treatment approved for use in the United States for treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement. Pemazyre is also indicated for the treatment of adults with relapsed or refractory previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a FGFR2 fusion or other rearrangement as detected by an FDA-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response (DOR). Continued approval may be contingent on verification and description of clinical benefit in a confirmatory trial(s). IMPORTANT SAFETY INFORMATION Ocular Toxicity Retinal Pigment Epithelial Detachment (RPED): PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visual floaters, or photopsia. Clinical trials of PEMAZYRE did not conduct routine monitoring including optical coherence tomography (OCT) to detect asymptomatic RPED; therefore, the incidence of asymptomatic RPED with PEMAZYRE is unknown. Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%. The median time to first onset of RPED was 56 days. RPED led to dose interruption of PEMAZYRE in 3.1% of patients, and dose reduction and permanent discontinuation in 1.3% and in 0.2% of patients, respectively. RPED resolved or improved to Grade 1 levels in 76% of patients who required dosage modification of PEMAZYRE for RPED. Perform a comprehensive ophthalmological examination including OCT prior to initiation of PEMAZYRE and every 2 months for the first 6 months and every 3 months thereafter during treatment. For onset of visual symptoms, refer patients for ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of PEMAZYRE. Modify the dose or permanently discontinue PEMAZYRE as recommended in the prescribing information for PEMAZYRE. Dry Eye: Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, dry eye occurred in 31% of patients, including Grade 3-4 in 1.6% of patients. Treat patients with ocular demulcents as needed. Hyperphosphatemia and Soft Tissue Mineralization PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE. Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, hyperphosphatemia was reported in 93% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-169). Phosphate lowering therapy was required in 33% of patients receiving PEMAZYRE. Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is >5.5 mg/dL. For serum phosphate levels >7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia as recommended in the prescribing information. Embryo-Fetal Toxicity Based on findings in an animal study and its mechanism of action, PEMAZYRE can cause fetal harm when administered to a pregnant woman. Oral administration of pemigatinib to pregnant rats during the period of organogenesis caused fetal malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 13.5 mg. Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose. Adverse Reactions: Cholangiocarcinoma Serious adverse reactions occurred in 45% of patients receiving PEMAZYRE (n=146). Serious adverse reactions in ≥2% of patients who received PEMAZYRE included abdominal pain, pyrexia, cholangitis, pleural effusion, acute kidney injury, cholangitis infective, failure to thrive, hypercalcemia, hyponatremia, small intestinal obstruction, and urinary tract infection. Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive, bile duct obstruction, cholangitis, sepsis, and pleural effusion. Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received PEMAZYRE. Adverse reactions requiring permanent discontinuation in ≥1% of patients included intestinal obstruction and acute kidney injury. Dosage interruptions due to an adverse reaction occurred in 43% of patients who received PEMAZYRE. Adverse reactions requiring dosage interruption in ≥1% of patients included stomatitis, palmar-plantar erythrodysesthesia syndrome, arthralgia, fatigue, abdominal pain, AST increased, asthenia, pyrexia, ALT increased, cholangitis, small intestinal obstruction, alkaline phosphatase increased, diarrhea, hyperbilirubinemia, electrocardiogram QT prolonged, decreased appetite, dehydration, hypercalcemia, hyperphosphatemia, hypophosphatemia, back pain, pain in extremity, syncope, acute kidney injury, onychomadesis, and hypotension. Dose reductions due to an adverse reaction occurred in 14% of patients who received PEMAZYRE. Adverse reactions requiring dosage reductions in ≥1% of patients who received PEMAZYRE included stomatitis, arthralgia, palmar-plantar erythrodysesthesia syndrome, asthenia, and onychomadesis. Clinically relevant adverse reactions occurring in ≤10% of patients included fractures (2.1%). In all patients treated with pemigatinib, 0.5% experienced pathologic fractures (which included patients with and without cholangiocarcinoma [N = 635]). Soft tissue mineralization, including cutaneous calcification, calcinosis, and non-uremic calciphylaxis associated with hyperphosphatemia were observed with PEMAZYRE treatment. Within the first 21-day cycle of PEMAZYRE dosing, serum creatinine increased (mean increase of 0.2 mg/dL) and reached steady state by Day 8, and then decreased during the 7 days off therapy. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed. In cholangiocarcinoma (n=146) the most common adverse reactions (incidence ≥20%) were hyperphosphatemia (60%), alopecia (49%), diarrhea (47%), nail toxicity (43%), fatigue (42%), dysgeusia (40%), nausea (40%), constipation (35%), stomatitis (35%), dry eye (35%), dry mouth (34%), decreased appetite (33%), vomiting (27%), arthralgia (25%), abdominal pain (23%), hypophosphatemia (23%), back pain (20%), and dry skin (20%). Adverse Reactions: Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement Serious adverse reactions occurred in 53% of patients receiving PEMAZYRE at all dosages (n=34). Serious adverse reactions in > 5% of patients included acute kidney injury. Fatal adverse reactions occurred in 9% of patients who received PEMAZYRE, including acute kidney injury, multiple organ dysfunction syndrome, and malignant neoplasm progression, occurring in one patient each. Permanent discontinuation due to an adverse reaction occurred in 12% of patients who received PEMAZYRE at all dosages. Adverse reactions requiring permanent discontinuation included cardiac failure, multiple organ dysfunction syndrome, blood alkaline phosphatase increase, and calciphylaxis. In patients who started treatment on the recommended dosage (n = 20), adverse reactions requiring dosage interruption of PEMAZYRE occurred in 80% of patients. Adverse reactions which required dosage interruption in > 2 patients treated at the recommended dosage included nail toxicities (20%) and hyperphosphatemia (15%). Dose reductions of PEMAZYRE due to an adverse reaction occurred in 80% of patients who started treatment on the recommended dosage. Adverse reactions requiring dose reductions occurring in > 2 patients were nail toxicities (20%), hyperphosphatemia (20%), and alopecia (15%). The most common (≥ 20%) adverse reactions were hyperphosphatemia (74%), nail toxicity (62%), alopecia (59%), stomatitis (53%), diarrhea (50%), dry eye (50%), fatigue (44%), rash (35%), abdominal pain (35%), anemia (35%), constipation (32%), dry mouth (32%), epistaxis (29%), retinal pigment epithelial detachment (26%), extremity pain (26%), decreased appetite (24%), dry skin (24%), dyspepsia (24%), back pain (24%), nausea (21%), blurred vision (21%), peripheral edema (21%), and dizziness (21%). Drug Interactions Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce the dose of PEMAZYRE if concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE. Special Populations Advise lactating women not to breastfeed during treatment with PEMAZYRE and for 1 week after the last dose. Reduce the recommended dose of PEMAZYRE for patients with severe renal impairment as described in the prescribing information. Reduce the recommended dose of PEMAZYRE for patients with severe hepatic impairment as described in the prescribing information. Please see Full Prescribing Information for PEMAZYRE. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. You may also report side effects to Incyte Medical Information at 1-855-463-3463. About Incyte Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte. Forward-Looking Statements Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding whether or when Pemazyre might provide a successful treatment option for patients with MLN with FGFR1 rearrangement, the Company’s ongoing clinical development program for pemigatinib, the FIGHT-203 clinical trial program, the LIMBER program and Incyte’s research in and approach to rare blood cancers and their treatment, contain predictions, estimates and other forward-looking statements. These forward-looking statements are based on the Company’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials and the ability to enroll subjects in accordance with planned schedules; the effects of the COVID-19 pandemic and measures to address the pandemic on the Company’s clinical trials supply chain and other third-party providers and development and discovery operations; determinations made by the FDA or other regulatory authorities; the Company’s dependence on its relationships with its collaboration partners; the efficacy or safety of the Company’s products and the products of the Company’s collaboration partners; the acceptance of the Company’s products and the products of the Company’s collaboration partners in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; and other risks detailed from time to time in the Company’s reports filed with the Securities and Exchange Commission, including its annual report and its quarterly report on Form 10-Q for the quarter ended June 30, 2022. The Company disclaims any intent or obligation to update these forward-looking statements. 1Gotlib J. World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management. Am J Hematol. 2017;92:1243-1259. 2Reiter A, Gotlib J. Myeloid neoplasms with eosinophilia. Blood. 2017;129(6):704–714.