On November 17, 2025 Syntara Limited (ASX: SNT), a clinical-stage drug development company, reported that it has received a positive opinion on the submission of Orphan Drug Designation (ODD) from the European Medicines Agency (EMA) for its advanced clinical asset amsulostat (SNT-5505) for the treatment of myelofibrosis (MF).

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An ODD grant will provide numerous incentives for Syntara in the European Union (EU) as it develops amsulostat, including ten years market exclusivity upon approval, clinical trial protocol assistance, access to the centralised authorisation procedure in Europe, and certain fee reductions.

Amsulostat already has ODD in the US from the Food & Drug Administration (FDA) for the treatment of MF.

Myelofibrosis is a disorder in which normal bone marrow tissue is gradually replaced with a fibrous scar-like material. Over time, this leads to progressive bone marrow failure. It can occur at any age but is usually diagnosed later in life, between the ages of 60 and 70 years, with its cause remaining largely unknown.

Syntara recently announced positive top-line Phase 2a data for amsulostat in MF, with patients sub optimally controlled on ruxolitinib with 73% achieving at least a 50% reduction in total symptom score, and nearly half showing meaningful spleen volume reduction after a year of treatment. This sustained improvement in clinical measures of efficacy is backed up by excellent tolerability and no treatment-related adverse events.

Syntara has received feedback from the FDA on a recommended pathway for further development, and is progressing a design for the next trial of amsulostat.

Syntara CEO Gary Phillips commented: "Receipt of this positive opinion for Orphan Drug Desgination in the EU comes after detailed review of the amsulostat pre-clinical and clinical dossier by the EMA, providing further validation of the potential that the drug has to benefit myelofibrosis patients. We continue to engage with our advisors and regulatory authorities to design a clinical trial that leverages the product’s strong differentiating features as a well-tolerated and effective therapy. Our goal is to ensure the study design is compelling for investors and strategic partners by clearly demonstrating how amsulostat can positively impact the current standard of care."

(Press release, Syntara, NOV 17, 2025, https://mcusercontent.com/add2e2fa70ec3d0eeaf2a93cc/files/42cc5d05-d389-5ba0-606c-034c87587de6/03023812.pdf [SID1234660003])

On November 17, 2025 Shanghai Henlius Biotech, Inc. (2696.HK), and Organon (NYSE: OGN) reported that the US Food and Drug Administration (FDA) has approved the Biologics License Application (BLA) for POHERDY (pertuzumab-dpzb) 420 mg/14 mL injection for intravenous use, an interchangeable biosimilar to PERJETA (pertuzumab), for all indications of the reference product.1 POHERDY is the first and only approved pertuzumab biosimilar in the US, representing an important milestone in expanding access to quality and potentially more affordable biologic therapies for patients with certain HER2-positive breast cancers.2

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"Expanding access to treatments for diseases that disproportionately impact women, including breast cancer, the most common cancer among women in the US excluding skin cancer, is at the core of our mission," said Jon Martin, US Commercial Lead, Biosimilars and Established Brands at Organon.3 "Not only is POHERDY the first approved biosimilar to PERJETA in the US, but its approval also builds on Organon’s recent momentum of expanding our biosimilars portfolio in women’s health and oncology. Our collaboration with Henlius is critical to our goal of making health care more sustainable for US patients."

"The FDA approval of POHERDY marks a significant milestone in Henlius’ global expansion and quality biologics development. As the first pertuzumab biosimilar approved in the US, this important achievement demonstrates our core capability to build a sustainable global R&D system grounded in rigorous scientific and regulatory standards. It also reflects Henlius’ steadfast commitment to its patient-centric philosophy and long-term global strategy," said Dr. Jason Zhu, Executive Director and Chief Executive Officer of Henlius. "We will continue accelerating the delivery of quality biologics to benefit more patients worldwide and create greater value for human health."2

"The approval of POHERDY further underscores Henlius’ track record in international registration, together with our strength in quality management and commercialization collaboration," said Ping Cao, Chief Business Development Officer and Senior Vice President of Henlius. "We look forward to working closely with our partner Organon to leverage our complementary strengths in supply chain, market, and distribution networks, jointly enhancing access to quality biologics and providing patients with treatment options that combine quality and affordability."2

POHERDY is a HER2/neu receptor antagonist indicated for use in combination with trastuzumab and docetaxel for the treatment of adults with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. POHERDY is also indicated for use in combination with trastuzumab and chemotherapy as (i) neoadjuvant treatment of adults with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer and (ii) adjuvant treatment of adults with HER2-positive early breast cancer at high risk of recurrence. See full indications below.

Pertuzumab products can cause subclinical and clinical cardiac failure manifesting as decreased left ventricular ejection fraction (LVEF) and congestive heart failure (CHF). Evaluate cardiac function prior to and during treatment. Discontinue POHERDY treatment for a confirmed clinically significant decrease in left ventricular function. Exposure to pertuzumab products can cause embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception. See additional safety information below.

POHERDY was approved based on the review of a comprehensive data package, which includes analytical similarity, clinical pharmacokinetic studies, and comparative clinical studies demonstrating that POHERDY is highly similar to and interchangeable with the reference product PERJETA in terms of safety, purity, and potency (safety and effectiveness).4,5

In 2022, Henlius entered into a license and supply agreement with Organon, granting Organon the exclusive commercialization rights to multiple biosimilars, including POHERDY. The agreement covers exclusive global commercialization rights except for China.6 The FDA approval of POHERDY will further enhance the partners’ oncology portfolio and their ability to deliver quality biologics to more patients.2

About POHERDY (pertuzumab-dpzb)

POHERDY is a HER2/neu receptor antagonist indicated for:

Metastatic Breast Cancer (MBC): POHERDY is indicated for use in combination with trastuzumab and docetaxel for the treatment of adults with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
Early Breast Cancer (EBC): POHERDY is indicated for use in combination with trastuzumab and chemotherapy for:
The neoadjuvant treatment of adults with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer
The adjuvant treatment of adults with HER2-positive early breast cancer at high risk of recurrence
SELECTED SAFETY INFORMATION

LEFT VENTRICULAR DYSFUNCTION and EMBRYO-FETAL TOXICITY

Pertuzumab products can cause subclinical and clinical cardiac failure manifesting as decreased left ventricular ejection fraction (LVEF) and congestive heart failure (CHF). Evaluate cardiac function prior to and during treatment. Discontinue POHERDY treatment for a confirmed clinically significant decrease in left ventricular function.
Exposure to pertuzumab products can cause embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception.
CONTRAINDICATIONS

POHERDY is contraindicated in patients with known hypersensitivity to pertuzumab products or to any of its excipients.

WARNINGS AND PRECAUTIONS

Left Ventricular Dysfunction

Pertuzumab products can cause left ventricular dysfunction, including symptomatic heart failure. Decreases in LVEF have been reported with drugs that block HER2 activity, including pertuzumab products.

Assess LVEF prior to initiation of POHERDY and at regular intervals during treatment to ensure that LVEF is within normal limits. If the LVEF declines and has not improved, or has declined further at the subsequent assessment, consider permanent discontinuation of POHERDY and trastuzumab.

In the pertuzumab-treated patients with MBC in CLEOPATRA, left ventricular dysfunction occurred in 4% of patients, and symptomatic left ventricular systolic dysfunction (LVSD) (congestive heart failure) occurred in 1% of patients. Patients who received prior anthracyclines or prior radiotherapy to the chest area may be at higher risk of decreased LVEF or left ventricular dysfunction.

In patients receiving pertuzumab as a neoadjuvant treatment in combination with trastuzumab and docetaxel in NeoSphere, LVEF decline >10% and a drop to <50% occurred in 8% of patients, and left ventricular dysfunction occurred in 3% of patients. LVEF recovered to ≥50% in all of these patients.

In patients receiving neoadjuvant pertuzumab in TRYPHAENA, LVEF decline >10% and a drop to <50% occurred in 7% of patients treated with pertuzumab plus trastuzumab and fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by pertuzumab plus trastuzumab and docetaxel, 16% of patients treated with pertuzumab plus trastuzumab and docetaxel following FEC, and 11% of patients treated with pertuzumab in combination with docetaxel, carboplatin, and trastuzumab (TCH). Left ventricular dysfunction occurred in 6% of patients treated with pertuzumab plus trastuzumab and FEC followed by pertuzumab plus trastuzumab and docetaxel, 4% of patients treated with pertuzumab plus trastuzumab and docetaxel following FEC, and 3% of patients treated with pertuzumab in combination with TCH. Symptomatic LVSD occurred in 4% of patients treated with pertuzumab plus trastuzumab and docetaxel following FEC, 1% of patients treated with pertuzumab in combination with TCH, and none of the patients treated with pertuzumab plus trastuzumab and FEC followed by pertuzumab plus trastuzumab and docetaxel. LVEF recovered to ≥50% in all but 1 patient.

In patients receiving neoadjuvant pertuzumab in BERENICE, in the neoadjuvant period, LVEF decline ≥10% and a drop to <50% as measured by ECHO/MUGA assessment occurred in 7% of patients treated with pertuzumab plus trastuzumab and paclitaxel following dose-dense doxorubicin and cyclophosphamide (ddAC) and 2% of patients treated with pertuzumab plus trastuzumab and docetaxel following FEC. Ejection fraction decreased (asymptomatic LVD) occurred in 7% of patients treated with pertuzumab plus trastuzumab and paclitaxel following ddAC and 4% of the patients treated with pertuzumab plus trastuzumab and docetaxel following FEC in the neoadjuvant period. Symptomatic LVSD (New York Heart Association [NYHA] Class III/IV Congestive Heart Failure) occurred in 2% of patients treated with pertuzumab plus trastuzumab and paclitaxel following ddAC and none of the patients treated with pertuzumab plus trastuzumab and docetaxel following FEC in the neoadjuvant period.

In patients receiving adjuvant pertuzumab in APHINITY, the incidence of symptomatic heart failure (NYHA Class III/IV) with a LVEF decline ≥10% and a drop to <50% was 0.6%. Of the patients who experienced symptomatic heart failure, 47% of pertuzumab-treated patients had recovered (defined as 2 consecutive LVEF measurements above 50%) at the data cutoff. The majority of the events (86%) were reported in anthracycline-treated patients. Asymptomatic or mildly symptomatic (NYHA Class II) declines in LVEF ≥10% and a drop to <50% were reported in 3% of pertuzumab-treated patients, of whom 80% recovered at the data cutoff.

Pertuzumab products have not been studied in patients with a pretreatment LVEF value of <50%; a prior history of CHF; decreases in LVEF to <50% during prior trastuzumab therapy; or conditions that could impair left ventricular function such as uncontrolled hypertension, recent myocardial infarction, serious cardiac arrhythmia requiring treatment, or a cumulative prior anthracycline exposure to >360 mg/m2 of doxorubicin or its equivalent.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings in animal studies, pertuzumab products can cause fetal harm when administered to a pregnant woman. Pertuzumab products are HER2/neu receptor antagonists. Cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported with use of another HER2/neu receptor antagonist (trastuzumab) during pregnancy.

Verify the pregnancy status of females of reproductive potential prior to the initiation of POHERDY. Advise pregnant women and females of reproductive potential that exposure to POHERDY in combination with trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm, including embryo-fetal death or birth defects. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of POHERDY in combination with trastuzumab.

Infusion-Related Reactions

Pertuzumab products can cause serious infusion reactions, including fatal events.

In CLEOPATRA, on the first day, when only pertuzumab was administered, infusion-related reactions occurred in 13% of patients, and <1% were Grade 3 or 4. The most common infusion reactions (≥1%) were pyrexia, chills, fatigue, headache, asthenia, hypersensitivity, and vomiting. During the second cycle when all drugs were administered on the same day, the most common infusion reactions in the pertuzumab-treated group (≥1%) were fatigue, dysgeusia, hypersensitivity, myalgia, and vomiting.

In APHINITY, when pertuzumab was administered in combination with trastuzumab and chemotherapy on the same day, infusion-related reactions occurred in 21% of patients, with <1% of patients experiencing Grade 3-4 events.

Observe patients closely for 60 minutes after the first infusion and for 30 minutes after subsequent infusions of POHERDY. If a significant infusion-related reaction occurs, slow or interrupt the infusion, and administer appropriate medical therapies. Monitor patients carefully until complete resolution of signs and symptoms. Consider permanent discontinuation in patients with severe infusion reactions.

Hypersensitivity Reactions/Anaphylaxis

Pertuzumab products can cause hypersensitivity reactions, including anaphylaxis.

In CLEOPATRA, the overall frequency of hypersensitivity/anaphylaxis reactions was 11% in pertuzumab-treated patients, with Grade 3-4 hypersensitivity reactions and anaphylaxis occurring in 2% of patients.

In NeoSphere, TRYPHAENA, BERENICE, and APHINITY, hypersensitivity/anaphylaxis events were consistent with those observed in CLEOPATRA. In APHINITY, the overall frequency of hypersensitivity/anaphylaxis was 5% in the pertuzumab-treated group. The incidence was highest in the pertuzumab plus TCH–treated group (8%), with 1% Grade 3-4 events.

Observe patients closely for hypersensitivity reactions. Severe hypersensitivity, including anaphylaxis and fatal events, has been observed in patients treated with pertuzumab products. Angioedema has been described in postmarketing reports. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use prior to administration of POHERDY.

ADVERSE REACTIONS

Metastatic Breast Cancer

The most common adverse reactions (>30%) with pertuzumab in combination with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.

Neoadjuvant Treatment of Breast Cancer

The most common adverse reactions (>30%) with pertuzumab in combination with trastuzumab and docetaxel were alopecia, diarrhea, nausea, and neutropenia.

The most common adverse reactions (>30%) with pertuzumab in combination with trastuzumab and docetaxel when given for 3 cycles following 3 cycles of FEC were fatigue, alopecia, diarrhea, nausea, vomiting, and neutropenia.

The most common adverse reactions (>30%) with pertuzumab in combination with TCH were fatigue, alopecia, diarrhea, nausea, vomiting, neutropenia, thrombocytopenia, and anemia.

The most common adverse reactions (>30%) with pertuzumab in combination with trastuzumab and paclitaxel when given for 4 cycles following 4 cycles of ddAC were nausea, diarrhea, alopecia, fatigue, constipation, peripheral neuropathy, and headache.

The most common adverse reactions (>30%) with pertuzumab in combination with trastuzumab and docetaxel when given for 4 cycles following 4 cycles of FEC were diarrhea, nausea, alopecia, asthenia, constipation, fatigue, mucosal inflammation, vomiting, myalgia, and anemia.

Adjuvant Treatment of Breast Cancer

The most common adverse reactions (>30%) with pertuzumab in combination with trastuzumab and chemotherapy were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting.

Before prescribing POHERDY, please read the Prescribing Information, including the Boxed Warning about left ventricular dysfunction and embryo-fetal toxicity.

(Press release, Shanghai Henlius Biotech, NOV 17, 2025, View Source [SID1234660043])

On November 17, 2025 ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ITM-94 ([68Ga]Ga-DPI-4452) as a diagnostic agent for the detection of clear cell renal cell carcinoma (ccRCC). The Fast Track designation was granted based on the potential of ITM-94 as a more effective, non-invasive diagnostic agent designed to improve outcomes for people living with ccRCC, a condition with high unmet medical need1.

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"The FDA’s Fast Track designation is a validation of ITM-94’s potential to aid in the non-invasive diagnosis of renal cell carcinoma," said Dr. Celine Wilke, chief medical officer of ITM. "We have seen promising data in our ongoing clinical trial that suggest ITM-94 could change how clinicians diagnose and stage patients across the broader ccRCC disease landscape, with potential utility in supporting clinical decision-making for indeterminate renal masses as well. This news highlights the innovation within our pipeline and the important role an effective diagnostic can play in cancer treatment."

ITM-94 is a gallium-68-radiolabeled PET imaging agent and, together with radiotherapeutic compound ITM-91 ([177Lu]Lu-DPI-4452), comprise a first-in-class, peptide-based theranostic pair. The theranostic pair targets carbonic anhydrase IX (CAIX), a cell surface protein that plays a key role in the tumor microenvironment, promoting tumor growth, survival, invasion and metastasis. ITM-94 is currently being evaluated in Part D of the ongoing Phase 1/2 clinical trial for its effectiveness to accurately detect ccRCC in patients with indeterminate renal masses (IDRM) when compared to CT/MRI imaging, with histopathological confirmation of diagnosis. Secondary endpoints include assessments of the imaging agent’s sensitivity, specificity and Positive Predictive Value (PPV) and Negative Predictive Value (NPV) compared to histology.

FDA Fast Track designation is designed to facilitate the development and expedite the review of new diagnostics and therapies that are intended to treat serious or life-threatening conditions and have the potential to address an unmet medical need. Programs granted this designation are eligible for more frequent communications with the FDA during clinical development and for accelerated approval and/or priority review over standard reviews if relevant criteria are met.

About the Phase 1/2 ITM-91/ITM-94 Trial
The multi-part clinical trial (NCT05706129) is designed to assess the safety and tolerability, imaging characteristics, and efficacy of the theranostic pair ITM-91/ITM-94 in patients with unresectable, locally advanced or metastatic solid tumors. In the first-in-human part of the trial (Part A), ITM-94 has demonstrated exceptional tumor imaging characteristics, with a high tumor-to-background ratio and a favorable tolerability profile in patients with confirmed ccRCC1. Part B is currently assessing increasing doses of the therapeutic agent, ITM-91, in ccRCC patients whose tumors show CAIX expression as evidenced by uptake of the imaging tracer, ITM-94. Based on the recommended dose and treatment schedule obtained from Part B, expansion Part C of the trial will evaluate the safety and preliminary efficacy of ITM-91 in patients with ccRCC, and potentially other CAIX-expressing tumor types. Part D is evaluating the effectiveness of ITM-94 in classifying indeterminate renal masses, such as ccRCC.

(Press release, ITM Isotopen Technologien Munchen, NOV 17, 2025, View Source [SID1234661165])

On November 17, 2025 Privo Technologies reported results from the CLN-004 Phase 2/3 (Cohort 1) trial evaluating PRV111, a nanoengineered, cisplatin-releasing patch for the treatment of non-invasive oral cancer and high-grade dysplasia (HGD). These conditions are common, recur frequently, and typically require repeated surgical excision, which can impair speech, swallowing, and appearance.

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In this trial, PRV111 delivered a 92% pathologic CR rate, eliminated the need for surgery in all patients, and demonstrated durable local control. Manijeh Goldberg, PhD, MBA, Founder and CEO of Privo Technologies, commented:
"The complete response rate achieved with PRV111 is among the highest reported for localized therapies in this setting. Patients typically face repeated surgical resections, which can lead to fibrosis, scar formation, and anatomic distortion that can permanently affect speech and other functionality. This non-surgical patch not only cleared the tumors but preserved native tissue function. These results reinforce PRV111’s potential to redefine the standard of care for oral precancer and early carcinoma in situs. We are one step closer to providing patients with an office-based, non-surgical alternative to repeated operative procedures."

The CLN-004 study builds upon Privo’s earlier clinical experience with PRV111 (CLN-001), which showed promising local tumor responses with no systemic toxicity in a first-in-human setting. The results of that earlier trial were published in Nature Communications and highlighted by Forbes for their innovative approach to localized cancer drug delivery.

Detailed Results:
Twelve patients with biopsy-confirmed non-invasive oral cancers or high-grade dysplasia received a single cycle of PRV111. Eleven patients achieved centrally confirmed pathologic CRs; the twelfth patient was down staged to low-grade dysplasia, eliminating the need for surgery. All treated lesions resolved, and mucosal surfaces regenerated without scarring or distortion. At a median follow-up of ~6 months, no recurrences were observed; several patients have maintained responses beyond six months, and the longest ongoing response now ~12 months. There were no systemic toxicities, dose-limiting toxicities, or treatment-related serious adverse events. Treatment-related events were primarily mild, transient oral symptoms.

Transforming the Treatment Paradigm:
Current management of non-invasive oral cancer and HGD relies on surgical excision, which is associated with high recurrence and morbidity. PRV111 is designed to deliver high concentrations of cisplatin directly into dysplastic tissue through a brief, office-based procedure, avoiding systemic side effects associated with traditional chemotherapy. This topical approach represents the first non-surgical alternative in development focused on treating this class of disease.

Next Steps:
Privo Technologies is initiating a registrational study of PRV111 in non-invasive oral cancers and high-grade dysplasias. The company will also explore PRV111 in other early malignant and premalignant lesions where non-surgical alternatives could provide significant benefits.

About PRV111:
PRV111 is a nanoengineered, polymeric topical patch designed to deliver high-dose cisplatin directly into oral lesions and adjacent mucosa while minimizing systemic exposure. The patch adheres to the lesion, achieves rapid drug permeation into dysplastic tissue and regional lymphatics, and is removed after treatment.

(Press release, Privo Technologies, NOV 17, 2025, View Source [SID1234660006])

On November 17, 2025 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, reported a peer-reviewed publication in the Journal of Hematology & Oncology of the final five-year data from the pivotal cohort of the Phase 2 registrational trial evaluating REZLIDHIA (olutasidenib) for the treatment of patients with relapsed or refractory (R/R) mutant isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML). REZLIDHIA is a potent, selective, oral, small-molecule inhibitor of mIDH11 that is approved for the treatment of R/R mIDH1 AML.

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The publication reports the final follow-up analysis of the registrational Phase 2 trial, with an additional two years of efficacy and safety data. These five-year data further support the durable responses and manageable safety profile observed with olutasidenib in patients with R/R mIDH1 AML, including those R/R to prior venetoclax. The safety profile remained consistent with what was previously reported, with no new safety signals identified.

"Since its launch, olutasidenib has become an important treatment option for patients with relapsed or refractory mIDH1 AML due to its clinical activity and durable responses, including patients previously treated with venetoclax who have particularly poor outcomes," said Jorge E. Cortes, M.D., Phase 2 trial investigator and Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer. "These incremental data support earlier findings and provide additional insights that further enhance the opportunity for olutasidenib to positively impact the outcome of patients with mIDH1 AML."

"This long-term final analysis of olutasidenib reinforces the potential for olutasidenib in mIDH1 AML," said Lisa Rojkjaer, M.D, Rigel’s chief medical officer. "The data to date demonstrates clinical benefit across a range of patients and underscores the importance of maintaining therapy for at least 6 months in the absence of toxicity or disease progression to optimize the ability to achieve a response."

Additional key points from the paper include:

For the overall population, the five-year safety profile of olutasidenib remained consistent, with no new safety signals identified compared to the three-year analysis, and no new cases of differentiation syndrome reported.
Of 147 efficacy evaluable patients, complete remission (CR) or CR with partial hematologic recovery (CRh) was achieved in 35%. The median duration of CR/CRh was 25.3 months. Overall response rate (ORR) was 48%, with median duration of 15.5 months. Median overall survival (OS) was 11.5 months.
Transfusion independence (for ≥56 days) from red blood cells was achieved in 34 patients (39%) who were dependent at baseline and for platelets was achieved in 28 patients (41%) who were dependent at baseline.
Among the 71 patients who achieved an overall response, 66% of patients achieved a response within 2 months, 24% required 2 to 4 months to respond and 10% required at least 4.6 (up to 10.2) months of therapy to achieve a response. Median OS was 32.7 months.
Patients with one to two prior regimens had a higher CR/CRh rate (41%), ORR (54%), and longer median OS (13 months) compared to those with ≥3 prior regimens (CR/CRh: 24%; ORR: 39%; median OS: 8.9 months).
In the 12 patients that were R/R to prior venetoclax, 33% achieved a CR/CRh; median duration of CR/CRh was not reached (3 patients ongoing at 22.6, 36.9 and 50.6 months), and median OS was 16.2 months.
The publication, titled "Olutasidenib for Mutated IDH1 Acute Myeloid Leukemia: Final Five-Year Results From the Phase 2 Pivotal Cohort," was published online and can be found here.

Rigel is also evaluating olutasidenib in other disease areas where mIDH1 plays a role. The company has strategic collaborations with The University of Texas MD Anderson Cancer Center (MD Anderson) and CONNECT, an international collaborative network of pediatric neuro-oncology centers. Latest updates include:

In September, the fifth study under the strategic alliance between Rigel and MD Anderson opened for enrollment. This Phase 2 multi-arm, multi-center, open-label, non-randomized clinical study will evaluate olutasidenib in combination with co-targeted therapies in patients with R/R IDH1-mutated myeloid malignancies harboring activated signaling pathway mutations (NCT07032727). The primary objectives of the study are to evaluate safety and the composite complete remission rate.
In October, the first patient was enrolled in the CONNECT Phase 2 TarGeT-D study evaluating olutasidenib in combination with temozolomide, followed by olutasidenib monotherapy as a maintenance regimen for newly-diagnosed adolescent and young adult patients with a high-grade glioma harboring an IDH1 mutation (NCT06161974).
About AML
Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 22,010 new cases in the United States, most in adults, in 2025.1

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.2,3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.

About REZLIDHIA

INDICATION
REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome
REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence.

Hepatotoxicity
REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin.

Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity.

ADVERSE REACTIONS
The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis.

DRUG INTERACTIONS

Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.
Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
LACTATION
Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.

GERIATRIC USE
No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.

HEPATIC IMPAIRMENT
In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome.

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REZLIDHIA is a registered trademark of Rigel Pharmaceuticals, Inc.

(Press release, Rigel, NOV 17, 2025, View Source [SID1234660028])