Full Press Release Details
Citius Pharmaceuticals, Inc. and Citius Oncology,
Inc. Announce LYMPHIR (Denileukin Diftitox-cxdl) Added to National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines
CRANFORD, N.J., Sept. 5, 2024 -- Citius
Pharmaceuticals, Inc. ("Citius Pharma" or the "Company") (Nasdaq: CTXR) and Citius Oncology, Inc. ("Citius Oncology")
(Nasdaq: CTOR), today announced that LYMPHIR has been added to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ).
LYMPHIR is included based on an NCCN Category 2A recommendation which indicates a uniform NCCN consensus that the drug is appropriate
as an option for patients with Cutaneous T-cell Lymphoma (CTCL).
LYMPHIR (denileukin diftitox-cxdl), a novel immunotherapy
for the treatment of relapsed or refractory CTCL after at least one prior systemic therapy, was recently approved by the U.S Food and
Drug Administration (FDA). The approval of LYMPHIR is based on results from the Phase 3 Pivotal Study 302 (NCT01871727) of CTCL patients
who had previously received at least one systemic treatment. LYMPHIR is the only CTCL therapy that targets the interleukin-2 (IL-2) receptor
found on malignant T-cells and Tregs.
"The inclusion of LYMPHIR in the NCCN Guidelines
is a testament to the clinical evidence supporting this therapy, and further supports healthcare professionals in considering LYMPHIR
as part of the recommended treatment protocols for CTCL. We are grateful to the NCCN board for its recognition of LYMPHIR, paving the
way for expanded access to this important treatment option," stated Leonard Mazur, CEO of Citius Pharma and Citius Oncology.
"NCCN guidelines are widely regarded as
the gold standard for clinical decision-making in oncology and hematology, influencing treatment practices and payor reimbursement in
the U.S. We believe that LYMPHIR has the potential to improve CTCL patient outcomes, and expect its addition to the NCCN Guidelines may
aid adoption and ease reimbursement, particularly for the anticipated patients that qualify for Center for Medicare and Medicaid (CMS)
coverage," added Mazur.
About LYMPHIR (denileukin diftitox-cxdl)
LYMPHIR is a targeted immune therapy for r/r (R/R)
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
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.
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 S zary 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.
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
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
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
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.
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.
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