On January 7, 2025 Johnson & Johnson (NYSE:JNJ) reported positive topline results for the gold standard endpoint in cancer treatment of overall survival (OS) from the Phase 3 MARIPOSA study, evaluating RYBREVANT (amivantamab-vmjw) plus LAZCLUZE (lazertinib) as a first-line therapy for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations (Press release, Johnson & Johnson, JAN 7, 2025, View Source [SID1234649479]). The chemotherapy-free combination regimen met the final pre-specified secondary endpoint of OS and demonstrated clinically meaningful and statistically significant improvement in OS versus the current standard of care osimertinib. Improvement in median OS is expected to exceed one year.

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Unlike progression-free survival (PFS), which tracks the time a treatment keeps a patient’s cancer from progressing, OS helps patients understand the impact therapy could have on the ability to live longer from the start of treatment. Extending life expectancy is the most meaningful indicator of a treatment’s impact.

"The combination of these two agents previously demonstrated an improvement in progression-free survival, but this does not always capture the impact on the entire treatment course. Evaluation of overall survival can better demonstrate the benefit of a first-line treatment regimen," said Stephen Liu, M.D.*, Associate Professor of Medicine at Georgetown University School of Medicine and Director of Thoracic Oncology and Head of Developmental Therapeutics at Georgetown’s Lombardi Comprehensive Cancer Center. "Seeing this increase in overall survival in a trial with mature data is powerful and reaffirms that first-line treatment with RYBREVANT and LAZCLUZE can lead to better patient outcomes."

"Every milestone in clinical trials and every approval of a new drug or regimen brings hope and progress for EGFR-positive patients and their families," said Marcia Horn**, President of International Cancer Advocacy Network. "These topline data from the MARIPOSA trial offer renewed optimism in the journey to extend life for EGFR-mutated patients, adding another important option for patients and oncologists."

"These new findings reinforce the clinically meaningful impact this chemotherapy-free regimen can have for patients worldwide with non-small cell lung cancer and represent the first overall survival benefit over the current standard of care," said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson Innovative Medicine. "With less than 20 percent of patients living beyond five years, an incredible unmet need remains for EGFR-positive lung cancer. These MARIPOSA results show RYBREVANT plus LAZCLUZE can extend survival beyond the current standard of care, providing patients with more time and hope in their fight against this devastating disease. Extending median overall survival by more than a year could be transformative for these patients."

Results from the final OS analysis build upon previously reported data from the interim analysis and positive results from the PFS analysis. MARIPOSA, which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT in combination with LAZCLUZE versus osimertinib as a first-line treatment of patients with EGFR-mutated NSCLC. The study’s primary endpoint was PFS (using RECIST v1.1 guidelines***) as assessed by blinded independent central review (BICR). Secondary endpoints included OS, objective response rate (ORR), duration of response (DOR), second progression-free survival (PFS2) and intracranial PFS.

The safety profile of RYBREVANT plus LAZCLUZE was generally consistent with the profiles of the individual treatments. Adverse event rates were consistent in this arm as compared to other RYBREVANT regimens. Venous thromboembolic events were observed with the combination. Subsequent studies showed that administering oral anticoagulant medicines prophylactically during the initial four months of the RYBREVANT and LAZCLUZE regimen significantly reduced the risk of thrombosis.

Due to the impact of these data on patient care, these OS results will be presented at an upcoming major medical meeting, and will be shared with global health authorities. RYBREVANT combined with LAZCLUZE is approved in the United States and Europe for the first-line treatment of patients with EGFR-mutated NSCLC based on the MARIPOSA Phase 3 study.

About RYBREVANT

RYBREVANT (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe and other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.1

RYBREVANT is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.

RYBREVANT is approved in the U.S. and Europe in combination with LAZCLUZE (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test.

RYBREVANT is approved in the U.S., Europe and other markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitors (TKI).

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include:

Amivantamab-vmjw (RYBREVANT) plus lazertinib (LAZCLUZE) as a Category 1 recommendation for first-line therapy in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.2†‡
Amivantamab-vmjw (RYBREVANT) plus chemotherapy as a Category 1 recommendation for patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.2†‡
Amivantamab-vmjw (RYBREVANT) plus chemotherapy as a Category 1 recommendation for first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC.2†‡
Amivantamab-vmjw (RYBREVANT) as a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.2†‡
For more information, visit: View Source

About LAZCLUZE

In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of LAZCLUZE (marketed as LACLAZA in Korea). LAZCLUZE is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR. An analysis of the efficacy and safety of LAZCLUZE from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023.

About Non-Small Cell Lung Cancer

Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.3,4 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.5 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.6 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.5,6,7,8,9,10 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.11 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.12,13 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.14 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.15

IMPORTANT SAFETY INFORMATION1,16

Before you receive RYBREVANT as a single agent or in combination, tell your healthcare provider about all of your medical conditions, including if you:

have a history of lung or breathing problems.
are pregnant or plan to become pregnant. RYBREVANT and LAZCLUZE can harm your unborn baby.
Females who are able to become pregnant:

Your healthcare provider should do a pregnancy test before you start treatment with RYBREVANT or RYBREVANT in combination with LAZCLUZE.
You should use effective birth control (contraception) during treatment and for 3 months after your final dose of RYBREVANT.
For patients receiving LAZCLUZE: You should use effective birth control (contraception) during treatment and for 3 weeks after your last dose of LAZCLUZE.
Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with RYBREVANT or LAZCLUZE.
Males who have female partners who are able to become pregnant:

You should use effective birth control during treatment and for 3 weeks after your last dose of LAZCLUZE.
are breastfeeding or plan to breastfeed. It is not known if RYBREVANT passes into your breast milk. Do not breastfeed during treatment and for 3 months after your last dose of RYBREVANT. It is not known if LAZCLUZE passes into your breast milk. Do not breastfeed during treatment and for 3 weeks after your last dose of LAZCLUZE.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

LAZCLUZE may affect the way other medicines work, and other medicines may affect how LAZCLUZE works.

You should not start or stop any medicine before you talk with your healthcare provider that prescribed LAZCLUZE.

How will I receive RYBREVANT?

RYBREVANT will be given to you by your healthcare provider by intravenous infusion into your vein.
Your healthcare provider will decide the time between doses as well as how many treatments you will receive.
Your healthcare provider will give you medicines before each dose of RYBREVANT to help reduce the risk of infusion-related reactions.
RYBREVANT may be given in combination with the medicines carboplatin and pemetrexed. If you have any questions about these medicines, ask your healthcare provider.
If your treatment with RYBREVANT is given in combination with LAZCLUZE (lazertinib), you should take your dose of LAZCLUZE by mouth anytime before your infusion with RYBREVANT.
If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.
How should I take LAZCLUZE?

Take LAZCLUZE exactly as your healthcare provider tells you to take it.
Take LAZCLUZE one (1) time each day. On the day RYBREVANT is also given, take LAZCLUZE anytime before receiving the RYBREVANT infusion.
You can take LAZCLUZE with or without food.
Swallow LAZCLUZE tablets whole. Do not crush, cut, or chew the tablets.
If you miss a dose of LAZCLUZE and:
it has been less than 12 hours, take the missed dose.
it has been more than 12 hours, skip the dose and take your next dose at your regularly scheduled time.
If you vomit a dose of LAZCLUZE, do not take an extra dose. Take your next dose at your regularly scheduled time.
LAZCLUZE may be given in combination with other anti-cancer medicines. If you have any questions about these medicines, ask your healthcare provider.
What should I avoid while receiving RYBREVANT and/or LAZCLUZE?

RYBREVANT and RYBREVANT in combination with LAZCLUZE can cause skin reactions. You should limit your time in the sun during and for 2 months after your treatment with RYBREVANT and/or LAZCLUZE. Wear protective clothing and use sunscreen during treatment with RYBREVANT and/or LAZCLUZE.

What are the possible side effects of RYBREVANT or LAZCLUZE?

RYBREVANT and LAZCLUZE may cause serious side effects, including:

infusion-related reactions. Infusion-related reactions are common with RYBREVANT and can be severe or serious. Tell your healthcare provider right away if you get any of the following symptoms during your infusion of RYBREVANT:

shortness of breath
fever
chills
nausea

flushing
chest discomfort
lightheadedness
vomiting

lung problems. RYBREVANT may cause lung problems that may lead to death. LAZCLUZE may also cause lung problems that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare provider right away if you get any new or worsening lung symptoms, including shortness of breath, cough, or fever.

blood clot problems. Blood clots are a serious, but common side effect of RYBREVANT, when given together with LAZCLUZE, may cause blood clots in the veins of your legs (deep vein thrombosis) or lungs (pulmonary embolism) that may lead to death. Your healthcare provider will start you on medicine to prevent blood clots for the first 4 months of treatment. Tell your healthcare provider right away if you have any signs and symptoms of blood clots, including swelling, pain or tenderness in the leg, sudden unexplained chest pain, or shortness of breath.

skin problems. RYBREVANT can cause severe rash; including blisters, peeling, skin pain and sores, redness, raised acne-like bumps, itching, and dry skin. LAZCLUZE may cause severe rash including redness, raised acne-like bumps, itching, and dry skin. You may use alcohol-free (isopropanol-free, ethanol-free) moisturizing cream to reduce the risk of skin problems. Tell your healthcare provider right away if you get any skin reactions. Your healthcare provider may treat you with a medicine(s) or send you to see a skin specialist (dermatologist) if you get skin reactions during treatment with RYBREVANT or LAZCLUZE. See "What should I avoid while receiving RYBREVANT and/or LAZCLUZE?"

eye problems. RYBREVANT may cause eye problems. LAZCLUZE may also cause eye problems. Tell your healthcare provider right away if you get symptoms of eye problems which may include:

eye pain
inflammation of eye lids
inflamed cornea (front part of the eye)
dry eyes
eye redness
blurred vision

changes in vision
itchy eyes
excessive tearing
sensitivity to light
new or worsening problems with vision
Your healthcare provider may send you to see an eye specialist (ophthalmologist) if you get new or worsening eye problems during treatment with RYBREVANT or LAZCLUZE. You should not use contact lenses until your eye symptoms are checked by a healthcare provider.

The most common side effects of RYBREVANT in combination with LAZCLUZE (lazertinib) include:

rash
infected skin around the nail
muscle and joint pain
sores in the mouth
swelling of hands, ankles, feet, face, or all of your body
unusual feeling in the skin (such as tingling or a crawling feeling)
feeling very tired

diarrhea
constipation
COVID-19
dry skin
bleeding
decreased appetite
itchy skin
nausea
changes in certain blood tests
The most common side effects of RYBREVANT when given in combination with carboplatin and pemetrexed include:

rash
infected skin around the nail
feeling very tired
nausea
sores in the mouth
constipation
swelling of hands, ankles, feet, face, or all of your body

decreased appetite
muscle and joint pain
vomiting
COVID-19
changes in certain blood tests
The most common side effects of RYBREVANT when given alone:

rash
infected skin around the nail
muscle and joint pain
shortness of breath
nausea
feeling very tired

swelling of hands, ankles, feet, face, or all of your body
sores in the mouth
cough
constipation
vomiting
changes in certain blood tests
LAZCLUZE may cause fertility problems in males and females, which may affect your ability to have children. Talk to your healthcare provider if this is a concern for you.

Your healthcare provider may temporarily stop, decrease your dose, or completely stop your treatment with RYBREVANT or LAZCLUZE if you have serious side effects.

These are not all of the possible side effects of RYBREVANT or LAZCLUZE.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of RYBREVANT:

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.

You can ask your healthcare provider or pharmacist for information about RYBREVANT that is written for health professionals.

General information about the safe and effective use of LAZCLUZE:

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use LAZCLUZE for a condition for which it was not prescribed. Do not give LAZCLUZE to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your pharmacist or healthcare provider for information about LAZCLUZE that is written for health professionals.

Please read full Prescribing Information for RYBREVANT.

Please read full Prescribing Information for LAZCLUZE.

On January 7, 2025 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported that the company will present at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco on Tuesday, January 14, 2025, at 6:00 p.m. ET (Press release, BioCryst Pharmaceuticals, JAN 7, 2025, View Source [SID1234649461]).

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Link to the live audio webcast and replay of the presentation may be accessed in the Investors & Media section of BioCryst’s website at www.biocryst.com.

On January 7, 2025 Esphera SynBio ("Esphera"), a synthetic biology company, reported the closing of a $2M USD seed financing round (Press release, Esphera SynBio, JAN 7, 2025, View Source [SID1234649480]). The financing builds on the Company’s advanced R&D activities and proceeds are directed at the identification of an initial cancer vaccine clinical candidate and general corporate purposes. Seed investors GKCC and FACIT supported the financing.

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Using synthetic biology, Esphera produces engineered exosomes through the expression of proprietary transgenes that serve as nanomedicines. Unlocking new possibilities in vaccine innovation, the company applies the technology platform for the development of therapeutics for cancer and infectious disease.

"This financing enables us to validate our vaccine platform and advance a potential best-in-class therapy for patients living with cancer," said Dr. Brian Lichty, co-founder and CEO of Esphera. "While our clear focus is on advancing toward future clinical trials, maximizing the broad potential of our technology will also necessitate the exploration of strategic partnerships."

Esphera’s innovative platform produces therapeutic nanomedicines that can act as powerful immunostimulants, delivering customized antigenic payloads to stimulate robust immune responses. These nanomedicines are designed to enhance the efficacy of vaccines, offering personalized solutions to combat infectious disease.

"With the fields of engineered exosomes and therapeutic vaccines undergoing rapid evolution, Esphera’s pioneering approach places the Company at the forefront of a transformative opportunity for patient care," said Dr. David O’Neill, Chair of the Board of Directors of Esphera and President of FACIT. "Esphera’s team of entrepreneurial scientific leaders has the experience required to build a strong pipeline of innovative therapeutics."

The Company is based on foundational intellectual property from the labs of Drs. Carolina Ilkow and John Bell at The Ottawa Hospital Research Institute and Dr. Lichty at McMaster University, and operates research facilities in Hamilton, Ontario and Ottawa, Ontario.

On January 7, 2025 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing the novel, selective AXL kinase inhibitor bemcentinib for lung cancer reported that the first patient has been included in a clinical trial sponsored by the Mays Cancer Center at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) (Press release, BerGenBio, JAN 7, 2025, View Source [SID1234649446]). The study is led by Josephine A. Taverna, MD, a thoracic oncologist at the Mays Cancer Center and Associate Professor in the Division of Hematology and Oncology at UT Health San Antonio.

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"Dr. Taverna’s research has shown that AXL and JAK-STAT3 work in tandem to transmit signals promoting tumor growth and metastasis in advanced lung cancer. We are pleased to see this research advancing into clinical application and believe this study aligns closely with BerGenBio’s strategic focus on addressing the significant unmet needs of lung cancer patients, including first-line Non-Small Cell Lung Cancer patients with mutations in the STK11 gene," said Olav Hellebø, Chief Executive Officer of BerGenBio.

The trial is designed to study BerGenBio’s bemcentinib in combination with pacritinib, which is a JAK2 inhibitor indicated for treatment of the bone marrow disorder myelofibrosis in patients with platelet counts below 50 x 109/L. It works by blocking certain growth factors and cytokines. Pacritinib is marketed in the United States as VONJO and owned by Swedish Orphan Biovitrum AB (Sobi) (STO: SOBI), a specialized international biopharmaceutical company. Bemcentinib is a first-in-class, selective, oral once-a-day inhibitor of AXL receptor tyrosine kinase, a promising therapeutic target for serious diseases.

The study will include patients with lung adenocarcinoma, the most common type of lung cancer in the United States, accounting for approximately 40% of all lung cancers. The study is funded by a grant from the National Cancer Institute (NCI) of the National Institutes of Health (NIH).

On January 7, 2025 Citius Pharmaceuticals, Inc. ("Citius Pharma" or the "Company") (Nasdaq: CTXR) and its oncology-focused subsidiary, Citius Oncology (Nasdaq: CTOR), reported significant progress in preparations for the commercial launch of LYMPHIR, an innovative immunotherapy for the treatment of adults with relapsed or refractory cutaneous T-cell lymphoma (CTCL) (Press release, Citius Pharmaceuticals, JAN 7, 2025, View Source [SID1234649462]). Management is focused on making LYMPHIR available to patients as quickly as possible, with preparations underway for launch in the first half of 2025.

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"Since LYMPHIR’s approval in August 2024, we have worked diligently toward supporting its successful launch. We are making significant progress to finalize our manufacturing, marketing, reimbursement and sales efforts. This is a pivotal inflection point as we transition from clinical development to revenue generation. Our strategy not only focuses on a successful U.S. market penetration, but also includes exploring additional growth opportunities, including licensing partnerships in key international markets, for which discussions are underway, expanded indications for LYMPHIR, in addition to LYMPHIR’s potential as a combination immunotherapy. Our unwavering goal remains to deliver substantial value to patients, healthcare providers, and shareholders by bringing this innovative cancer treatment to market," stated Leonard Mazur, Chairman and CEO of Citius Pharmaceuticals and Citius Oncology.

Key Launch Preparations and Activities:

● Manufacturing Scale-Up and Supply Chain Optimization:

o Secured commercial supply agreements with leading contract manufacturing organizations (CMOs).

o First Year Launch Supply has been produced.

● Healthcare Provider Engagement:

o Rolled out targeted education programs aimed at oncologists, hematologists, and other key medical professionals.

o Launched an information platform that offers clinical data, dosing guidelines, and safety information for healthcare providers.

● Market Access and Reimbursement Efforts:

o Working closely with payers and healthcare providers to secure reimbursement pathways that facilitate patient access.

o Submitted an application for a unique J-code under the Healthcare Common Procedure Coding System (HCPCS) to streamline reimbursement processes.

o Secured LYMPHIR’s inclusion in the National Comprehensive Cancer Network (NCCN) guidelines, a key factor in influencing clinical decision-making and payer coverage in the U.S.

● Patient Support Initiatives:

o Designed a patient assistance program to help with financial support and access to LYMPHIR.

o Developing a best-in-class patient services center to assist LYMPHIR patients with administrative and prescribing needs.

● Marketing and Sales Initiatives:

o Launched a core marketing campaign to raise awareness among healthcare providers, ensuring that top CTCL prescribers are informed of LYMPHIR’s availability.

o Building an experienced specialized field sales team to partner with CTCL providers and office staff.

About LYMPHIR (denileukin diftitox-cxdl)

LYMPHIR is a targeted immune therapy for relapsed or refractory cutaneous T-cell lymphoma (CTCL) indicated for use in Stage I-III disease after at least one prior systemic therapy. It is a recombinant fusion protein that combines the IL-2 receptor binding domain with diphtheria toxin fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Denileukin diftitox-cxdl demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) and antitumor activity through a direct cytocidal action on IL-2R-expressing tumors.

In 2021, denileukin diftitox received regulatory approval in Japan for the treatment of CTCL and PTCL. Subsequently, in 2021, Citius acquired an exclusive license with rights to develop and commercialize LYMPHIR in all markets except for Japan and certain parts of Asia. LYMPHIR was approved by the FDA in August 2024.

About Cutaneous T-cell Lymphoma

Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL) that comes in a variety of forms and is the most common type of cutaneous lymphoma. In CTCL, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and develop into skin lesions, leading to a decrease in the quality of life of patients with this disease due to severe pain and pruritus. Mycosis Fungoides (MF) and Sézary Syndrome (SS) comprise the majority of CTCL cases. Depending on the type of CTCL, the disease may progress slowly and can take anywhere from several years to upwards of ten to potentially reach tumor stage. However, once the disease reaches this stage, the cancer is highly malignant and can spread to the lymph nodes and internal organs, resulting in a poor prognosis. Given the duration of the disease, patients typically cycle through multiple agents to control disease progression. CTCL affects men twice as often as women and is typically first diagnosed in patients between the ages of 50 and 60 years of age. Other than allogeneic stem cell transplantation, for which only a small fraction of patients qualify, there is currently no curative therapy for advanced CTCL.

INDICATION

LYMPHIR is an IL2-receptor-directed cytotoxin indicated for the treatment of adult patients with r/r Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: CAPILLARY LEAK SYNDROME

Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity.

WARNINGS AND PRECAUTIONS

Capillary Leak Syndrome

LYMPHIR can cause capillary leak syndrome (CLS), including life-threatening or fatal reactions. CLS was defined in the clinical trials as the occurrence of at least 2 of the following symptoms at any time during LYMPHIR therapy: hypotension, edema, and serum albumin <3 g/dL. These symptoms were not required to occur simultaneously to be characterized as capillary leak syndrome.

As defined, CLS occurred in 27% of patients in the pooled population across 3 clinical trials, including 8% with Grade 3. There was one (0.8%) fatal occurrence of CLS. Of the patients with CLS, 22% had recurrence. The majority of CLS events (81%) occurred within the first 2 cycles of treatment. The median time to onset from Cycle 1, Day 1 was 6.5 days (range: 1 to 77), the median duration of CLS was 14 days (range: 2 to 40), and 75% of patients had resolution. The most common symptoms included edema, hypoalbuminemia, and hypotension. Pleural effusion, pericardial effusion, and dehydration also occurred.

Regularly assess patients for weight gain, new onset or worsening of edema, dyspnea, and hypotension (including orthostatic changes). Monitor serum albumin levels prior to the initiation of each cycle of therapy and more often as clinically indicated.

Withhold, reduce dose, or permanently discontinue based on severity. If LYMPHIR is withheld, resume LYMPHIR following resolution of CLS and when serum albumin is greater than or equal to 3 g/dL.

Visual Impairment

LYMPHIR can cause serious visual impairment, including changes in visual acuity and color vision. In the pooled population across 3 clinical trials, visual impairment occurred in 9%, with Grade 1 in 8% and Grade 2 in 1%. The most commonly reported symptom was blurred vision. Of the patients with visual impairment, 67% had resolution of their visual impairment.

Perform baseline ophthalmic examination and monitor as clinically indicated. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, or blurred vision, refer for ophthalmologic evaluation.

Withhold LYMPHIR until visual impairment resolves or permanently discontinue based on severity.

Infusion-Related Reactions

LYMPHIR can cause serious infusion-related reactions. Infusion-related reactions were reported in 69% of patients in the pooled population across 3 clinical trials of patients who received LYMPHIR, with Grade 3 infusion-related reactions in 3.4% [see Adverse Reactions (6.1)]. Eighty-three percent of infusion-related reactions occurred in Cycles 1 and 2. The most common symptoms included nausea, fatigue, chills, musculoskeletal pain, vomiting, fever, and arthralgia.

Premedicate patients for the first three cycles prior to starting a LYMPHIR infusion [see Dosage and Administration (2.3)]. Monitor patients frequently during infusion. For Grade 2 or higher infusion reactions, premedicate at least 30 minutes prior to each subsequent infusion with a systemic steroid for at least 3 cycles.

Interrupt or discontinue LYMPHIR based on severity [see Dosage and Administration (2.4)]. Institute appropriate medical management.

Hepatotoxicity

LYMPHIR can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in 70% of patients, with Grade 3 ALT occurring in 22%; elevated AST occurred in 64% of patients, with Grade 3 AST elevation occurring in 9%. For Grade 3 events, median time to onset was 8 days (range: 1 to 15 days); median time to resolution was 15 days (range: 7 to 50 days); all cases of Grade 3 ALT or AST elevations resolved [see Adverse Reactions (6.1)]. Elevated total bilirubin occurred in 5% of patients, with Grade 3 occurring in 0.9%.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold, reduce dose, or permanently discontinue LYMPHIR based on severity.

Embryo-Fetal Toxicity

Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to the initiation of LYMPHIR. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for 7 days following the last dose of LYMPHIR.

ADVERSE REACTIONS

The most common adverse reactions (≥20%), including laboratory abnormalities, are increased transaminases, albumin decreased, nausea, edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary

Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman. There are no available data on the use of LYMPHIR in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with denileukin diftitox.

Denileukin diftitox-cxdl causes depletion of regulatory T lymphocytes (Treg), immune activation, and capillary leak syndrome, compromising pregnancy maintenance. Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

Lactation

Risk Summary

No data are available regarding the presence of denileukin diftitox-cxdl in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with LYMPHIR and for 7 days after the last dose.

Females and Males of Reproductive Potential

Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman.

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating LYMPHIR.

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with LYMPHIR and for 7 days after the last dose.

Infertility

Males

Based on findings in rats, male fertility may be compromised by treatment with. The reversibility of the effect on fertility is unknown.

Pediatric Use

Safety and effectiveness of LYMPHIR in pediatric patients have not been established.

Geriatric Use

Of the 69 patients with Stage I-III r/r CTCL who received LYMPHIR, 34 patients (49%) were 65 years of age and older and 10 patients (14%) were 75 years of age and older. Clinical studies of LYMPHIR did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Citius Pharmaceuticals at 1-844-459-6744.

Please read Important Safety Information and full Prescribing Information, including Boxed WARNING, for LYMPHIR.