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Samsung Bioepis Presents Long-Term Safety Data of EPYSQLI™ (Eculizumab) in PNH at the European Hematology Association (EHA) Congress 2025

On June 12, 2025 Samsung Bioepis Co., Ltd. ("Samsung Bioepis") reported the long-term safety data of EPYSQLI (eculizumab; SB12), a biosimilar to Soliris1, in paroxysmal nocturnal hemoglobinuria (PNH) at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress 2025 held at Milan, Italy from June 12 to 15 (Press release, Samsung Bioepis, JUN 12, 2025, View Source [SID1234653870]).

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EPYSQLI was approved by the European Commission (EC) for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) in May 2023 and March 2024, respectively2.

The study assessed the long-term safety of EPYSQLI in PNH patients by evaluating the consistency of safety outcomes, particularly serious adverse events (SAEs) between the initial 52-week Phase 3 study period and the extended treatment (ET) period, spanning from 52 weeks to up to 158 weeks. The same maintenance dose of 900 mg EPYSQLI was administered every 2 weeks. A total of 46 patients from the Phase 3 study received ET. During ET, seven patients (15.2%) experienced a total of 14 SAEs with no occurrence of fatal cases, and all patients fully recovered without permanently discontinuing the treatment. The exposure-adjusted event rate (EAER) was comparable between initial 52-week period and ET period (EAER were 0.13 and 0.17, respectively), and there was no statistically difference between initial 52-week and ET period in EAER (p-value = 0.76). The study is consistent with the findings of the Phase 3 study with no newly identified safety signals and no fatal cases occurred throughout the entire treatment period with all SAEs resolving completely.

Details of the abstract are as follows3:

Abstract title: Long-Term Safety of SB12 in Paroxysmal Nocturnal Hemoglobinuria: Up to 2-year Extension Treatment Safety Data
Abstract number: PB2811
Type: Publication Only
Session title: Bone marrow failure syndromes incl. PNH – Clinical
Author(s): Jun Ho Jang, Siook Baek, Yumin Baek, Jinah Jung, Ciprian Tomuleasa, Hanna Oliynyk, Theerin Lanamtieng, Soo Min Lim
Besides approval by the EC, EPYSQLI is also approved by the U.S. Food and Drug Administration (FDA) and Korea’s Ministry of Food and Drug Safety (MFDS) as a biosimilar to Soliris. In countries where EPYSQLI is approved and available, EPYSQLI may not be prescribed and/or dispensed for its unapproved other indications for which Soliris is approved.

About EPYSQLI (Eculizumab Biosimilar) in the European Union (EU)
EPYSQLI is indicated in adults and children for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). EPYSQLI is not approved for and should not be used for the treatment of generalised myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). EPYSQLI must be administered by a healthcare professional and under the supervision of a physician experienced in the management of patients with hematological disorders or renal disorders.

EPYSQLI EU Important Safety Information
The EU Summary of Product Characteristics for EPYSQLI includes the following Special warning and Precautions:

Meningococcal Infection
Due to its mechanism of action, the use of eculizumab increases the patient’s susceptibility to meningococcal infection (Neisseria meningitidis). Meningococcal disease due to any serogroup may occur. To reduce the risk of infection, all patients must be vaccinated at least 2 weeks prior to receiving eculizumab unless the risk of delaying eculizumab therapy outweighs the risks of developing a meningococcal infection. Patients who initiate eculizumab treatment less than 2 weeks after receiving a tetravalent meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Vaccines against serogroups A, C, Y, W 135 are recommended in preventing the commonly pathogenic meningococcal serogroups. Vaccine against serogroup B where available is also recommended. Patients must receive vaccination according to current national vaccination guidelines for vaccination use.

Vaccination may further activate complement. As a result, patients with complement-mediated diseases, including PNH and aHUS, may experience increased signs and symptoms of their underlying disease, such as haemolysis (PNH) or TMA (aHUS). Therefore, patients should be closely monitored for disease symptoms after recommended vaccination.

Vaccination may not be sufficient to prevent meningococcal infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents. Cases of serious or fatal meningococcal infections have been reported in eculizumab-treated patients. Sepsis is a common presentation of meningococcal infections in patients treated with eculizumab. All patients should be monitored for early signs of meningococcal infection, evaluated immediately if infection is suspected, and treated with appropriate antibiotics if necessary. Patients should be informed of these signs and symptoms and steps taken to seek medical care immediately.

Other Systemic Infections
Patients may have increased susceptibility to other type of serious infections, especially with Neisseria and encapsulated bacteria.

Infusion Reactions
Administration of eculizumab may result in infusion reactions or immunogenicity that could cause allergic or hypersensitivity reactions (including anaphylaxis). Eculizumab administration should be interrupted in all patients experiencing severe infusion reactions and appropriate medical therapy administered.

Anticoagulant therapy
Treatment with eculizumab should not alter anticoagulant management.

PNH Laboratory Monitoring
PNH patients should be monitored for signs and symptoms of intravascular haemolysis, including serum lactate dehydrogenase (LDH) levels, and may require dose adjustment within the recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days).

aHUS Laboratory Monitoring
aHUS patients receiving eculizumab therapy should be monitored for thrombotic microangiopathy by measuring platelet counts, serum LDH and serum creatinine, and may require dose adjustment within the recommended 14±2 day dosing schedule during the maintenance phase (up to every 12 days).

Treatment Discontinuation for PNH
If patients discontinue treatment with eculizumab they should be closely monitored for signs and symptoms of serious intravascular haemolysis.

Treatment Discontinuation for aHUS
If aHUS patients discontinue treatment with eculizumab, they should be monitored closely for signs and symptoms of severe thrombotic microangiopathy complications.

The most common adverse reaction observed with eculizumab treatment in clinical trials was headache, (occurred mostly in the initial phase of dosing), and the most serious adverse reaction was found to be meningococcal infection.

Refer to the Summary of Product Characteristics for EPYSQLI’s full safety information.

Schrödinger Reports Encouraging Initial Phase 1 Clinical Data for SGR-1505 at EHA Annual Congress

On June 12, 2025 Schrödinger, Inc. (Nasdaq: SDGR) reported encouraging initial clinical data from its ongoing Phase 1, open-label, dose-escalation study of SGR-1505 in patients with relapsed/refractory B-cell malignancies (Press release, Schrodinger, JUN 12, 2025, View Source [SID1234653869]). SGR-1505 was observed to be safe, well tolerated, and clinically active, with responses observed in multiple histologies, including in patients with chronic lymphocytic leukemia (CLL) and Waldenström macroglobulinemia (WM). These data are being presented in a poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress.

"We are very encouraged by the initial results from our Phase 1 study in patients with relapsed/refractory B-cell malignancies. The data presented today, coupled with the differentiated preclinical and safety profiles observed in our previously completed study in healthy volunteers, further increases our conviction about the potential for SGR-1505 to be a best-in-class therapy," said Margaret Dugan, M.D., chief medical officer at Schrödinger. "Dose escalation is complete, and we look forward to discussing these results and our proposed recommended Phase 2 dose with the FDA later this year."

"Despite recent advances in the treatment of B-cell malignancies, resistance to currently available therapies eventually results in treatment failure and disease progression for many patients," said Stephen Spurgeon, M.D., Associate Professor of Medicine, Oregon Health and Science University, and an investigator for the clinical study. "We know that MALT1 plays a critical role in key signaling pathways that drive cancer cell survival and proliferation, making it a promising target for a broad range of B-cell malignancies. Although these data are from an early-phase study, they suggest SGR-1505 demonstrates on-target activity resulting in potential clinical benefit. I look forward to seeing additional data as the study progresses, including response data in patients with aggressive histologies."

"The positive data reported today represent a key milestone for Schrödinger and follow the clinical successes of programs advanced by collaboration partners and companies we have co-founded," said Karen Akinsanya, Ph.D., president, head of therapeutics R&D and chief strategy officer, partnerships at Schrödinger. "These data reinforce the power of Schrödinger’s platform to enable the rapid design of differentiated molecules and the impact that our computational approach can have on a drug discovery and development program."

Major Takeaways from the Study

As of the data cut-off date, May 13, 2025, 49 patients were enrolled and evaluable for safety, including 18 patients with CLL/SLL, nine with diffuse large B-cell lymphoma (DLBCL), six with Waldenström macroglobulinemia (WM), and five with marginal zone lymphoma (MZL).
Patients had a median of four (range two-nine) prior lines of therapy, with the most common being Bruton’s tyrosine kinase (BTK) inhibitors (55.1%), BCL-2 inhibitors (18.4%) and BTK+BCL-2 inhibitors (18.4%).
SGR-1505 was well-tolerated with no dose-limiting toxicities or deaths due to treatment-emergent adverse events (TEAEs). Forty three percent of patients (n=21) experienced ≥ 1 treatment-related adverse event (TRAE), with the most common (≥ 10%) being rash (12%) and fatigue (12%). Ten patients (20%) experienced treatment-emergent serious adverse events (SAEs); one was treatment-related. All blood bilirubin increased TEAEs were asymptomatic, reported in patients with UGT1A1 polymorphisms and none were Grade 4.
Inhibition of IL-2 is a pharmacodynamic biomarker for target engagement and an exploratory endpoint in the study. Preliminary data indicated that SGR-1505 inhibits T-cell derived IL-2 upon ex vivo stimulation achieving the PD target of ~90% inhibition in the majority of PD-evaluable participants treated at ≥ 150 mg QD and all Q12H doses at steady state.
Preliminary efficacy data indicated SGR-1505 was clinically active as a monotherapy in a number of relapsed/refractory B-cell malignancies. Of the 49 participants, 45 patients had at least one follow-up disease assessment or disease progression and were evaluable for preliminary efficacy. The overall response rate (ORR) across all dose levels was 22% (n = 10/45). Thirteen of 49 patients had been on treatment for ≥120 days.
Among patients with indolent disease, 3/17 CLL/SLL, 5/5 WM, and 1/5 MZL patients responded. The responses of the three CLL responders were independently reviewed and confirmed, and two had a partial response (PR) with lymphocytosis (PR-L). Two of three CLL patients with partial responses were double-exposed to BTK and BCL-2 inhibitors, and all WM patients were exposed to BTK inhibitors.
The study recently began enrolling patients with aggressive lymphomas into the 300 mg QD and 100 mg Q12H cohorts. A PR was reported in one of four ABC-DLBCL patients.
Study Design
The Phase 1 dose-escalation study (NCT05544019) assessed SGR-1505 as a monotherapy treatment in patients with relapsed/refractory B-cell malignancies. The primary endpoint is the incidence and severity of adverse events and dose-limiting toxicities. Secondary endpoints include pharmacokinetic and pharmacodynamic measurements as well as objective response rate, duration of response and disease control rate.

EHA Poster Presentation Details
The full abstract (#PS1569) can be found online at www.ehaweb.org.

Poster Title: A Phase 1 study of SGR-1505, an oral, potent, MALT1 inhibitor for relapsed/refractory (R/R) B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL)
Presentation Date and Time: Saturday, June 14, 2025, 6:30-7:30PM CST (12:30-1:30PM ET)
Location: Poster Session 2

About SGR-1505
SGR-1505 is an oral investigational MALT1 inhibitor being evaluated for the treatment of relapsed/refractory B-cell malignancies. MALT1 plays a central role in key signaling pathways that drive cancer cell survival and proliferation, making its location downstream of BTK in the NF-κB signaling pathway an attractive target for the development of novel therapeutics for a potentially broad range of B-cell malignancies. In preclinical studies, SGR-1505 was observed to be highly potent and selective, and has demonstrated anti-tumor activity in preclinical models both as a monotherapy and in combination with BTK and BCL-2 inhibitors. There is also emerging therapeutic rationale supporting MALT1 inhibition as a potential treatment for inflammatory and autoimmune disorders.

SGR-1505 was designed using Schrödinger’s computational platform at scale and was discovered approximately 10 months after the company started its MALT1 program. Schrödinger believes that SGR-1505 is currently the most advanced MALT1 inhibitor known to be in clinical development and has both first-in-class and best-in-class potential. A Phase 1 study in patients with relapsed/refractory B-cell malignancies is ongoing (NCT05544019).

Webcast and Conference Call Information
Schrödinger will host a conference call on Thursday, June 12, 2025, at 8:00 a.m. ET to review the clinical opportunity for SGR-1505 and review the Phase 1 data presented at EHA (Free EHA Whitepaper). The live webcast can be accessed under "Events & Presentations" in the investors section of Schrödinger’s website, View Source To participate in the live call, please register for the call here. It is recommended that participants register at least 15 minutes in advance of the call. The archived webcast will be available on Schrödinger’s website for approximately 90 days following the event.

Debiopharm and Alkyon Therapeutics Announce Research Collaboration to Advance the Next Generation of Radioligand Therapies

On June 12, 2025 Debiopharm (www.debiopharm.com), a privately-owned Swiss biopharmaceutical company committed to establishing tomorrow’s standard of care to cure cancer and infectious diseases and Alkyon Therapeutics, Inc., a biotechnology company pioneering precision-targeted therapies, reported the signing of a co-research agreement to evaluate the feasibility of developing targeted radioligand therapies (RLTs) using Debiopharm’s proprietary AbYlink conjugation technology for Alkyon’s modular antibody platform directed against undisclosed tumor-associated antigens (Press release, Debiopharm, JUN 12, 2025, View Source [SID1234653868]).

This collaboration marks a promising step toward a new generation of RLTs designed to deliver potent radiation targeted directly to cancer cells while minimizing damage to healthy tissues. By leveraging the unique strengths of both platforms, the goal is to create more effective, better-tolerated cancer treatments that improve patient quality of life and expand therapeutic options for difficult-to-treat tumors. AbYLink technology enables regio-selective lysine conjugation, ensuring the radioligand avoids the target binding site and facilitating streamlined, consistent manufacturing.

"We’re intrigued to explore the potential of applying AbYlink conjugation technology to the radio-oncology field," expressed Frederic Levy, Chief Scientific Officer, Debiopharm. "Leveraging our innovative conjugation platform with Alkyon’s engineered antibody scaffolds could open new possibilities for next-generation radiopharmaceuticals with enhanced precision and therapeutic impact."

"This collaboration reflects our shared commitment to expanding the potential of radioligand therapies," said Benjamin Titz, Co-Founder and CEO of Alkyon Therapeutics. "By applying AbYlink to our specialized antibody scaffolds and targeting strategies tailored to the unique architecture of solid tumors, we aim to unlock new therapeutic possibilities and advance care for patients with difficult-to-treat solid tumors."

About AbYlink

AbYlink is a versatile and rapid regio-selective chemical conjugation technology for use in preparing diagnostic or therapeutic conjugates. This one-step method results in stable conjugation at defined and invariable sites on the Fc domain of an antibody or the like, with no impact on antigen-binding regions. It enables a seamless and reproducible conjugation of payloads (e.g., a chelator for radiolabeling, a fluorescent dye or a drug) to antibodies or ADCs. The universal applicability of the technology has been demonstrated for various antibody isotypes and payloads.

Silence Therapeutics Presents Additional Phase 1 Data Highlighting Promise of Divesiran as the Potential First-in-Class siRNA Treatment for Polycythemia Vera

On June 12, 2025 Silence Therapeutics plc ("Silence" or the "Company") (Nasdaq: SLN), a global clinical-stage company developing novel siRNA (short interfering RNA) therapies, reported additional data showcasing the SANRECO Phase 1 study of divesiran in patients with polycythemia vera (PV) at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Annual Meeting in Milan, Italy (Press release, Silence Therapeutics, JUN 12, 2025, View Source [SID1234653867]).

"The latest data presented at EHA (Free EHA Whitepaper) today continue to demonstrate divesiran’s potential to maintain rapid and durable control of hematocrit and essentially eliminate the need for phlebotomies in phlebotomy-dependent PV patients," said Marina Kremyanskaya, MD, PhD, Associate Professor of Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mount Sinai. "These early findings also suggest the potential for infrequent dosing and continue to support a favorable safety profile. I’m very encouraged by the consistency of the Phase 1 dataset and look forward to further development."

"Divesiran continues to demonstrate a very compelling profile as the first-in-class siRNA for PV," said Craig Tooman, President and Chief Executive Officer at Silence Therapeutics. "We are extremely encouraged by the support we are garnering from the physician community and that’s reflected in the positive momentum we’re seeing in the SANRECO Phase 2 study. The Phase 2 study is over 50-percent enrolled, and we remain on-track to complete patient enrollment by the end of this year."

Summary of Updated SANRECO Phase 1 Study Results

Results included 21 phlebotomy-dependent PV patients with a combined history of 79 phlebotomies prior to dosing. Therapeutic phlebotomies were essentially eliminated and mean hematocrit (HCT) levels were lowered and maintained to ≤ 45% for all cohorts regardless of baseline levels.
Divesiran increased hepcidin and ferritin, resulting in elevation of iron body content and improved iron deficiency.
Divesiran demonstrated similar results in all patient groups, independent of baseline risk or prior and concurrent therapy.
White blood cells were not altered over the time-course of the study.
Platelets increased, reaching a plateau with no dose dependent effect.
Divesiran was well tolerated with no dose-limiting toxicities.
SANRECO Phase 1 Study Design
The Phase 1 portion of SANRECO was a 34-week, open-label study evaluating divesiran (3 mg/kg, 6 mg/kg and 9 mg/kg) administered subcutaneously every 6 weeks for four doses, with a 16-week follow-up period following the date of the last administered dose in 21 PV patients. Key inclusion criteria included a PV diagnosis and a history of requiring at least three phlebotomies in the last six months or five in the last year prior to screening. Patients were allowed to be on stable doses of cytoreductive agents. Given the exploratory nature of this Phase 1 study, both well-controlled patients – defined as those with HCT levels at 45% or less – as well as those with HCT levels greater than 45% at baseline on current standard of care treatment were enrolled.

SANRECO Phase 2 Study Design
The Phase 2 portion of SANRECO is now enrolling PV patients and is a randomized, double-blind study evaluating two different divesiran regimens versus placebo. Key inclusion criteria include a PV diagnosis and a history of requiring at least three phlebotomies in the last seven months or five in the last year prior to dosing. Patients are allowed to be on stable doses of cytoreductive agents. Patients must have HCT levels less than 45% prior to dosing. For more information, please click here.

About PV
PV is a rare, myeloproliferative neoplasm – a type of blood cancer – characterized by the excessive production of red blood cells, often resulting in elevated hematocrit levels. Elevated hematocrit above 45-percent is associated with a four-times higher rate of death from cardiovascular or thrombotic events. PV is associated with a range of burdensome symptoms including fatigue, cognitive disturbance and pruritus and additionally, longer term can transform to myelofibrosis and Acute Myeloid Leukemia. The aim of treatment is to maintain hematocrit less than 45%, a level that is associated with a reduced incidence of thrombosis and CV-associated death. The current standard of care includes repeated phlebotomies to reduce hematocrit and/or cytoreductive agents to reduce red blood cell production. There are currently no approved therapies that specifically target red blood cells and hematocrit.

About Divesiran
Divesiran is Silence’s wholly owned siRNA product candidate developed from its proprietary mRNAi GOLD platform that "silences" TMPRSS6 expressed almost exclusively in the liver. TMPRSS6 is a negative regulator of hepcidin, the body’s master regulator of iron metabolism including its absorption, distribution, and storage. By silencing TMPRSS6 in PV patients, divesiran aims to increase hepcidin production and release by liver hepatocytes, leading to the restriction of iron to the bone marrow and, thus, reducing the excessive production of red blood cells, a process dependent on availability of iron. Divesiran is currently in Phase 2 development for PV and has FDA Fast Track and Orphan Drug designations for PV.

Phase 3 Data for Incyte’s Retifanlimab (Zynyz®) in Patients with Squamous Cell Carcinoma of the Anal Canal (SCAC) Published in The Lancet

On June 12, 2025 Incyte (Nasdaq:INCY) reported that primary results from the Phase 3 POD1UM-303/InterAACT 2 trial of retifanlimab (Zynyz), a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), in combination with carboplatin and paclitaxel (platinum-based chemotherapy) in adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal cancer (SCAC) who have not been previously treated with systemic chemotherapy, were published in The Lancet (Press release, Incyte, JUN 12, 2025, View Source [SID1234653866]).

"The publication of the POD1UM-303/InterAACT 2 trial in The Lancet is a testament to the strength of the data generated for retifanlimab in patients with inoperable locally recurrent or metastatic SCAC, a disease which until recently had seen limited innovation for decades," said Steven Stein, M.D., Chief Medical Officer, Incyte. "SCAC can be a devastating disease, and patients often have a poor prognosis. These data supported the U.S. Food and Drug Administration (FDA) approval of Zynyz (retifanlimab-dlwr) in May 2025, providing U.S. patients the first and only first-line treatment for inoperable locally recurrent or metastatic SCAC."

The POD1UM-303/InterAACT2 trial results, which were also featured at a Presidential Symposium on Practice-Changing Trials at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) in 2024, showed that the study met its primary endpoint by demonstrating a statistically significant improvement in progression-free survival (PFS) in patients with inoperable locally recurrent or metastatic SCAC not previously treated with systemic chemotherapy, as assessed by blinded independent central review (BICR) using RECIST v1.1.2 Adding retifanlimab to carboplatin and paclitaxel resulted in a clinically meaningful 37% reduction in the risk of progression or death (Hazard Ratio [HR]: 0.63; 95% Confidence Interval [CI] (0.47, 0.84); P=0.0006).2 Patients in the retifanlimab and chemotherapy combination group achieved a median PFS of 9.3 months compared to 7.4 months for patients in the placebo combination group.2

New data published today in The Lancet show that in patients treated with retifanlimab plus chemotherapy:1

A consistent benefit in PFS in favor of retifanlimab plus chemotherapy was observed for all pre-defined subgroups with sufficient patients for comparison.
A clinically meaningful 6-month difference in overall survival (OS) was observed at the interim analysis (29.2 months in the retifanlimab plus carboplatin and paclitaxel group vs 23.0 months in the placebo plus carboplatin and paclitaxel group). Interim OS results were not statistically significant, and patients continue to be followed for the final key secondary OS analysis.
The overall response rate (ORR) to treatment was improved by the addition of retifanlimab to the chemotherapy (55.8% in the retifanlimab plus carboplatin and paclitaxel group vs 44.2% in the placebo plus carboplatin and paclitaxel group) and the median duration of response was approximately doubled (14 months in the retifanlimab plus carboplatin and paclitaxel group vs 7.2 months in the placebo plus carboplatin and paclitaxel group) when compared to placebo.
As reported in The Lancet, no new safety signals were observed in POD1UM-303/InterAACT2, and safety was consistent with chemotherapy plus checkpoint inhibitor regimens. Serious and Grade 3 or worse adverse events were more frequent in the retifanlimab plus carboplatin and paclitaxel group compared with placebo plus carboplatin and paclitaxel group (47.4% vs 38.8% and 83.1% vs 75.0%, respectively). The most common Grade ≥3 adverse events were neutropenia (35.1% for retifanlimab plus carboplatin and paclitaxel vs 29.6% for placebo plus carboplatin and paclitaxel) and anemia (19.5% vs 20.4%). Despite the higher rate of serious, Grade 3 or worse, and fatal adverse events with retifanlimab plus carboplatin and paclitaxel than placebo plus carboplatin–paclitaxel, these toxicities were manageable with standard measures and carboplatin and paclitaxel delivery was not compromised.

The publication, entitled "Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3 randomised controlled trial," can be found online here.

"The incidence of SCAC is increasing by approximately 3% annually, driven mainly by endemic human papillomavirus (HPV infection). With no approved treatments available for advanced cases until recently, it is crucial to develop effective therapies for this orphan disease," said Sheela Rao, M.D., Consultant Medical Oncologist, The Royal Marsden National Health Service Foundation Trust.

In May 2025, the FDA approved Zynyz (retifanlimab-dlwr) in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic SCAC. In addition, the FDA granted approval for Zynyz as a single agent for the treatment of adult patients with locally recurrent or with metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy. Incyte has also submitted a Type II variation Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for retifanlimab in advanced SCAC and in March 2025 submitted and received acceptance of a Japanese New Drug Application (J-NDA) by the Pharmaceuticals and Medical Devices Agency (PMDA) for retifanlimab in advanced SCAC.

About Squamous Cell Carcinoma of the Anal Canal (SCAC)

SCAC is the most common type of anal cancer, making up 85% of cases.3 It is a rare disease for which the incidence is increasing approximately 3% per year.4 About 90% of cases are associated with human papillomavirus (HPV) infection—the number one risk factor for anal cancer.5 HIV is an important amplifier of anal cancer, as people with HIV are 25 to 35 times more likely to develop it.6,7 Anal cancer shares many of the same symptoms as non-cancerous conditions, such as hemorrhoids—including pain, itching, a lump or mass and changes in bowel movements—and as a result can go undetected leading to the majority of patients presenting with locally advanced disease.8,9 More information about SCAC is available by visiting www.analcancer.com.

About POD1UM

The POD1UM (PD1 Clinical Program in Multiple Malignancies) clinical trial program for retifanlimab includes POD1UM-303, POD1UM-202 and several other Phase 1, 2 and 3 studies for patients with solid tumors, including a registration-directed trial evaluating retifanlimab in combination with platinum-based chemotherapy for patients with non-small cell lung cancer.

About POD1UM-303/InterAACT 2

POD1UM-303/InterAACT 2 (NCT04472429) is a Phase 3, randomized, multicenter, double-blind, placebo-controlled study evaluating retifanlimab or placebo in combination with platinum-based chemotherapy (carboplatin and paclitaxel) in adult patients with inoperable locally recurrent or metastatic SCAC who have not been previously treated with systemic chemotherapy.

During the blinded portion of the study, patients, including those with well-controlled HIV infection, were randomized 1:1 to receive retifanlimab 500 mg intravenously or placebo during each 28-day cycle for up to 6 months in combination with standard therapy of carboplatin and paclitaxel, followed by retifanlimab or placebo monotherapy for up to 1-year total treatment in the absence of disease progression or unacceptable toxicity. Crossover to retifanlimab monotherapy was allowed for patients assigned to placebo upon verification of progression by blinded independent central review (BICR).

The primary endpoint was progression-free survival (PFS) as determined by BICR using RECIST v1.1. The key secondary endpoint was overall survival (OS). Other secondary endpoints include objective response rate (ORR), duration of response (DOR), disease control rate (DCR) by BICR, safety and pharmacokinetics.

For more information about the study, please visit View Source

About Zynyz (retifanlimab-dlwr)

Zynyz (retifanlimab-dlwr) is a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), indicated in combination with carboplatin and paclitaxel (platinum-based chemotherapy) for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) and as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression or intolerance to platinum-based chemotherapy in the U.S.

Zynyz is also indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) in the U.S. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Zynyz is marketed by Incyte in the United States. In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab.

Zynyz is a registered trademark of Incyte.

Important Safety Information

What is the most important information I should know about Zynyz?

Zynyz is a medicine that may treat certain types of cancers by working with your immune system. Zynyz can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your doctor right away if you develop any new or worsening signs or symptoms, including:

Lung problems: cough, shortness of breath, chest pain

Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, sticky, or have blood or mucus; severe stomach-area (abdomen) pain or tenderness

Liver problems: yellowing of your skin or the whites of your eyes; severe nausea or vomiting; pain on the right side of your stomach area (abdomen); dark urine (tea colored); bleeding or bruising more easily than normal

Hormone gland problems: headaches that will not go away or unusual headaches; eye sensitivity to light; eye problems; rapid heartbeat; increased sweating; extreme tiredness; weight gain or weight loss; feeling more hungry or thirsty than usual; urinating more often than usual; hair loss; feeling cold; constipation; your voice gets deeper; dizziness or fainting; changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness

Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, loss of appetite

Skin problems: rash; itching; skin blistering or peeling; painful sores or ulcers in your mouth or nose, throat, or genital area; fever or flu-like symptoms; swollen lymph nodes

Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with Zynyz. Call or see your doctor right away for any new or worsening signs or symptoms, which may include:

chest pain, irregular heartbeat, shortness of breath, or swelling of ankles
confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
persistent or severe muscle pain or weakness, muscle cramps
low red blood cells, bruising
Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include: chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain.

Rejection of a transplanted organ or tissue. Your doctor should tell you what signs and symptoms you should report and monitor you, depending on the type of organ or tissue transplant that you have had.

Complications, including graft-versus-host disease, in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with Zynyz. Your doctor will monitor you for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. Your doctor will check you for these problems during your treatment. Your doctor may treat you with corticosteroid or hormone replacement medicines and may also need to delay or completely stop treatment if you have severe side effects.

Before you receive Zynyz, tell your doctor about all of your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant or tissue transplant, including corneal transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to your chest area
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. Zynyz can harm your unborn baby
Females who are able to become pregnant:

Your doctor should do a pregnancy test before you start treatment.
You should use an effective method of birth control during your treatment and for 4 months after your last dose. Talk to your doctor about birth control methods that you can use during this time.
Tell your doctor right away if you become pregnant or think you may be pregnant during treatment.
are breastfeeding or plan to breastfeed. It is not known if Zynyz passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of Zynyz when given with the chemotherapy medicines carboplatin and paclitaxel in people with SCAC include tiredness, numbness, pain, tingling, or burning in your hands or feet; nausea; hair loss; diarrhea; muscle and bone pain; constipation; bleeding; rash; vomiting; decreased appetite; itching; stomach-area pain.

The most common side effects of Zynyz when used alone in people with SCAC include tiredness, muscle and bone pain, diarrhea, infection, rectal or genital-area pain, bleeding, urinary tract infection (UTI), rash, nausea, loss of appetite, constipation, stomach-area pain, shortness of breath, fever, vomiting, cough, itching, low levels of thyroid hormone, headache, decreased weight.

The most common side effects of Zynyz when used alone in people with MCC include tiredness, muscle and bone pain, itching, diarrhea, rash, fever, nausea.

These are not all the possible side effects of Zynyz. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Incyte Corporation at 1-855-463-3463.

General information about the safe and effective use of Zynyz

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about Zynyz, talk with your doctor. You can ask your doctor for information about Zynyz that is written for health professionals.

Please see the full Prescribing Information, including the Medication Guide, for Zynyz.

You may also report side effects to the FDA View Source or to Incyte Corporation at 1-855-463-3463.