A Randomized, Dose-Ranging, Double Blind Study to Demonstrate the Safety and Efficacy of a CITI-002 Cream in the Seven Day Twice-Daily Treatment of Grade II or III Hemorrhoids

A Randomized Phase 2 double blind study which aims to determine the safety and efficacy of CITI-002 cream in adult patients with Goligher's grade II or III hemorrhoids.

开始日期2022-04-22

申办/合作机构

Citius Pharmaceuticals, Inc.

[+1]

100 项与醋酸氢化可的松/盐酸利多卡因相关的临床结果

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100 项与醋酸氢化可的松/盐酸利多卡因相关的转化医学

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100 项与醋酸氢化可的松/盐酸利多卡因相关的专利（医药）

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项与醋酸氢化可的松/盐酸利多卡因相关的文献（医药）

2002-10-01·Canadian journal of anaesthesia = Journal canadien d'anesthesie3区 · 医学

Total spinal anesthesia provides transient relief of intractable pain

3区 · 医学

Article

作者: Satoshi Mizobuchi ; Yoshio Kusume ; Katsunori Oe ; Masataka Yokoyama ; Kiyoshi Morita ; Yoshitaro Itano

PURPOSE:

Intentional total spinal anesthesia (TSA) has been used for intractable pain treatment. However, the long-term effect of pain-relief is controversial. We investigate the short- and long-term effects of pain-relief by TSA.

METHODS:

Twelve patients with intractable pain participated in a crossover study. All participants received two different treatments in random order at a 30-day interval: i.v. infusion with 300 mg of lidocaine (i.v.-Lido), and TSA with 20 mL of 1.5% lidocaine (TSA-Lido). Pain level at rest was scored with the visual analogue scale (VAS: 0-100), and blood pressure and heart rate were measured before and at two hours, 24 hr, seven days, and 30 days after treatment. Plasma lidocaine concentrations were measured at 0.5, one, and two hours.

RESULTS:

Heart rate and mean arterial pressure during or after TSA-Lido were similar to those before TSA-Lido. Plasma lidocaine concentrations were similar between the two treatments. No significant difference in any value occurred in the i.v.-Lido treatment. VAS were similar before both treatments (87 +/- 6 for TSA-Lido; 86 +/- 7 for i.v.-Lido). After TSA-Lido, VAS decreased significantly until day seven (two hours, 17 +/- 22, P < 0.01; 24 hr, 43 +/- 20, P < 0.01; seven days, 66 +/- 16, P < 0.01). However, VAS returned to the pre-block values 30 days after TSA-Lido.

CONCLUSION:

Intractable pain was decreased significantly for several days after TSA, but pain-relief was not sustained.

1995-11-01·Journal of the American Dental Association (1939)3区 · 医学

ASSESSING THE DURATION OF MANDIBULAR SOFT TISSUE ANESTHESIA

3区 · 医学

Article

作者: Johnson, P D ; Hermann, D G ; Hersh, E V ; MacAfee, K A ; Lamp, C J

Dentists often employ solutions of 3 percent mepivacaine or 4 percent prilocaine without a vasoconstrictor in pediatric patients in an attempt to reduce the duration of mandibular soft tissue anesthesia. The authors compared the time course of soft tissue anesthesia produced by these solutions with that of 2 percent lidocaine plus 1:100,000 epinephrine in 60 adults. They found no reduction in the duration of soft tissue anesthesia when employing 3 percent mepivacaine or 4 percent prilocaine instead of 2 percent lido-epi. Combining these observations with local anesthetic dosage considerations, the authors recommend that 2 percent lido-epi be used when performing mandibular block injections in young children.

Frontiers in pharmacology2区 · 医学

Lido-OH, a Hydroxyl Derivative of Lidocaine, Produced a Similar Local Anesthesia Profile as Lidocaine With Reduced Systemic Toxicities

2区 · 医学

ArticleOA

作者: Yin, Qinqin ; Liu, Jin ; Zhang, Wensheng ; Zhang, Weiyi ; Ke, Bowen

Background: lidocaine is one of the most commonly used local anesthetics for the treatment of pain and arrhythmia. However, it could cause systemic toxicities when plasma concentration is raised. To reduce lidocaine’s toxicity, we designed a hydroxyl derivative of lidocaine (lido-OH), and its local anesthesia effects and systemic toxicity in vivo were quantitively investigated.Method: the effectiveness for lido-OH was studied using mouse tail nerve block, rat dorsal subcutaneous infiltration, and rat sciatic nerve block models. The systemic toxicities for lido-OH were evaluated with altered state of consciousness (ASC), arrhythmia, and death in mice. Lidocaine and saline were used as positive and negative control, respectively. The dose-effect relationships were analyzed.Results: the half effective-concentration for lido-OH were 2.1 mg/ml with 95% confident interval (CI95) 1.6–3.1 (lidocaine: 3.1 mg/ml with CI95 2.6–4.3) in tail nerve block, 8.2 mg/ml with CI95 8.0–9.4 (lidocaine: 6.9 mg/ml, CI95 6.8–7.1) in sciatic nerve block, and 5.9 mg/ml with CI95 5.8–6.0 (lidocaine: 3.1 mg/ml, CI95 2.4–4.0) in dorsal subcutaneous anesthesia, respectively. The magnitude and duration of lido-OH were similar with lidocaine. The half effective doses (ED50) of lido-OH for ACS was 45.4 mg/kg with CI95 41.6–48.3 (lidocaine: 3.1 mg/kg, CI95 1.9–2.9), for arrhythmia was 16.0 mg/kg with CI95 15.4–16.8 (lidocaine: 3.0 mg/kg, CI95 2.7–3.3), and for death was 99.4 mg/kg with CI95 75.7–124.1 (lidocaine: 23.1 mg/kg, CI95 22.8–23.4). The therapeutic index for lido-OH and lidocaine were 35.5 and 5.6, respectively.Conclusion: compared with lidocaine, lido-OH produced local anesthesia at similar potency and efficacy, but with significantly reduced systemic toxicities.

项与醋酸氢化可的松/盐酸利多卡因相关的新闻（医药）

2024-11-11

·PRNewswire

Citius Pharmaceuticals, Inc. and Citius Oncology, Inc. Announce Promising Preliminary Results of an Investigator-Initiated Phase I Clinical Trial of Pembrolizumab (KEYTRUDA®) and LYMPHIR™ in Cancer Patients with Recurrent Solid Tumors

Study, in patients with solid tumors focusing on gynecological malignant tumors such as ovarian, endometrial, and cervical, nearing completion with three remaining subjects to be enrolled27% Objective Response Rate (ORR)33% Clinical Benefit Rate (CBR) with a median Progression Free Survival (PFS) of 57 weeksChemotherapy-free immunomodulatory regimen well-tolerated with no documented serious immune-related adverse events CRANFORD, N.J., Nov. 11, 2024 /PRNewswire/ -- Citius Pharmaceuticals, Inc. ("Citius Pharma" or the "Company") (Nasdaq: CTXR) and Citius Oncology, Inc. ("Citius Oncology") (Nasdaq: CTOR), today announced promising preliminary results from an ongoing investigator-initiated Phase I clinical trial evaluating the safety and efficacy of a combined regimen of pembrolizumab and LYMPHIR™ (denileukin diftitox-cxdl or E7777) in patients with recurrent solid tumors. The data was summarized in a poster presentation titled "T-regulatory Cell Depletion with E7777 (denileukin diftitox-xcdl) Combined with Pembrolizumab in patients with recurrent solid tumors: Phase I trial" presented at the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting held November 8-10, 2024 (Abstract 614). Continue Reading Citius Oncology logo (PRNewsfoto/Citius Pharmaceuticals, Inc.) The trial is being conducted by Haider Mahdi, M.D., Assistant Professor, Department of Obstetrics, Gynecology & Reproductive Sciences, at the University of Pittsburgh. The study aims to identify an optimal dose for future trials and explore the impact of a treatment regimen combining pembrolizumab and LYMPHIR on the tumor immune microenvironment. "We have seen promising results in patients with heavily pre-treated recurrent or metastatic gynecologic tumors and will enroll three additional patients before completing the Phase I portion of this study," said Mahdi. "We will further investigate in patients with gynecologic tumors and those with other solid tumor histologies. We want to explore the impact of this therapy on Tregs, host immune-effector cells and the tumor microenvironment." "The preliminary results from this Phase I trial of patients with recurrent gynecological cancers are highly encouraging. This novel chemo-free immunomodulatory combination regimen has been well tolerated, including at the highest dosage. This efficacy data strongly suggests that LYMPHIR may have the ability to improve and prolong the anti-tumor activity of immune checkpoint inhibitors. To date, this unique regimen has not been associated with significant immune-related adverse events. Moreover, of the 15 evaluable patients, one third experienced a clinical benefit with a median of more than 12 months of progression free survival," stated Dr. Myron Czuczman, Chief Medical Officer of Citius Pharmaceuticals and Citius Oncology. "There is reason to be optimistic about the potential of LYMPHIR to boost a patient's response to pembrolizumab by temporarily depleting Tregs that modulate the tumor microenvironment, without triggering an autoimmune response from the patient's body. We believe the positive signals from this data support expanding the research in a Phase II study to further evaluate the combination's benefits across a broader range of solid tumor types," he added. PD-1 inhibitors such as pembrolizumab are a type of immune checkpoint inhibitor that works by blocking the PD-1 protein on T cells, enabling the immune system to recognize and attack cancer cells. Pembrolizumab, developed by Merck and sold under the brand name KEYTRUDA®, is the leading PD-1 inhibitor and world's most prescribed drug, generating $25 billion in sales in 2023. Preliminary Results The results of this chemotherapy-free regimen combining two immuno-modulator agents, pembrolizumab (anti-PD-1) and LYMPHIR (transient Treg depletion) demonstrated: An overall response rate (ORR) of 27% (4/15) and a clinical benefit rate of 33% (5/15) among evaluable patients; and, Median progression-free survival (PFS) for patients achieving clinical benefit of 57 weeks, with a range of 30 to 96 weeks. Notably, two of the four patients who achieved partial remission had received prior checkpoint inhibitors (i.e. anti-PD-1 therapy). This highlights the therapeutic potential of LYMPHIR plus immune checkpoint inhibitors to be effective in patients who fail prior anti-PD-1/L1 therapy. The trial enrolled 21 patients with recurrent or metastatic solid tumors. Among the evaluable participants, four patients achieved a partial response, and one patient demonstrated durable stable disease lasting over six months. The combination regimen was generally well tolerated, with most adverse events related to the patients' underlying disease. Importantly, no significant immune-related adverse events were observed, and only one case of dose-limiting toxicity (capillary leak syndrome) was reported at the highest dose level (12 mcg/kg). Table 1: Efficacy Data Table 2: Safety Data Trial Design The Phase I trial is an open-label study designed to evaluate the safety and preliminary efficacy of pembrolizumab, an anti PD-1 inhibitor, in combination with LYMPHIR in patients with recurrent or metastatic solid tumors. The trial employs a dose-escalation approach, with LYMPHIR administered in four dose levels (3, 6, 9, and 12 mcg/kg) in combination with pembrolizumab (200 mg) on a 21-day cycle for eight cycles. Following the combination regimen, patients receive pembrolizumab monotherapy as maintenance therapy. The study utilizes the Time-to-Event Continual Reassessment Method (TITE-CRM) to assess dose-limiting toxicities (DLTs) and determine the recommended Phase II dose (RP2D). Key inclusion criteria include measurable disease, ECOG performance status of 0-1, and adequate organ function. Patients with recurrent or metastatic solid tumors who have received at least one prior line of therapy were eligible for enrollment. The trial enrolled patients with a variety of recurrent or metastatic solid tumors, including ovarian, endometrial, and cervical cancers. Ovarian Cancer: Ovarian cancer is the eighth most common cancer in women worldwide, with an estimated 324,000 new cases diagnosed annually. In the United States, approximately 240,000 women are currently living with ovarian cancer. Endometrial Cancer: Worldwide, approximately 420,000 new cases are diagnosed each year. Endometrial cancer is the most common gynecologic cancer in the United States, with approximately 66,000 new cases diagnosed each year. It is estimated that over 600,000 women in the U.S. are living with endometrial cancer. Cervical Cancer: Cervical cancer remains a major health concern globally, with around 660,000 new cases annually. It is the fourth most common cancer among women. In the United States, approximately 11,500 women are diagnosed each year. 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. 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 . 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™. Please see Prescribing Information for KEYTRUDA® (pembrolizumab) and Medication Guide for KEYTRUDA. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. About Citius Oncology, Inc. Citius Oncology, Inc. (Nasdaq: CTOR) is a platform to develop and commercialize novel targeted oncology therapies. In August 2024, its primary asset, LYMPHIR, was approved by the FDA for the treatment of adults with relapsed or refractory CTCL who had had at least one prior systemic therapy. Management estimates the initial market for LYMPHIR currently exceeds $400 million, is growing, and is underserved by existing therapies. Robust intellectual property protections that span orphan drug designation, complex technology, trade secrets and pending patents for immuno-oncology use as a combination therapy with checkpoint inhibitors would further support Citius Oncology's competitive positioning. For more information, please visit . About Citius Pharmaceuticals, Inc. Citius Pharmaceuticals, Inc. (Nasdaq: CTXR) is a biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products. In August 2024, the FDA approved LYMPHIR, a targeted immunotherapy for an initial indication in the treatment of cutaneous T-cell lymphoma. Citius Pharma's late-stage pipeline also includes Mino-Lok®, an antibiotic lock solution to salvage catheters in patients with catheter-related bloodstream infections, and CITI-002 (Halo-Lido), a topical formulation for the relief of hemorrhoids. A Pivotal Phase 3 Trial for Mino-Lok and a Phase 2b trial for Halo-Lido were completed in 2023. Mino-Lok met primary and secondary endpoints of its Phase 3 Trial. Citius is actively engaged with the FDA to outline next steps for both programs. Citius Pharmaceuticals owns 92% of Citius Oncology. For more information, please visit . Forward-Looking Statements This press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements are made based on our expectations and beliefs concerning future events impacting Citius. You can identify these statements by the fact that they use words such as "will," "anticipate," "estimate," "expect," "plan," "should," and "may" and other words and terms of similar meaning or use of future dates. Forward-looking statements are based on management's current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated, and, unless noted otherwise, that apply to Citius Pharma and Citius Oncology, are: risks relating to the results of research and development activities, including those from our existing and any new pipeline assets; risks related to research using our assets but conducted by third parties; our need for substantial additional funds; Citius Pharma's ability to meet Nasdaq's continued listing standards; our ability to commercialize LYMPHIR and any of our other product candidates that may be approved by the FDA; the estimated markets for our product candidates and the acceptance thereof by any market; the ability of our product candidates to impact the quality of life of our target patient populations; our dependence on third-party suppliers; our ability to procure cGMP commercial-scale supply; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; uncertainties relating to preclinical and clinical testing; the early stage of products under development; market and other conditions; risks related to our growth strategy; patent and intellectual property matters; our ability to identify, acquire, close and integrate product candidates and companies successfully and on a timely basis; government regulation; competition; as well as other risks described in our SEC filings. These risks have been and may be further impacted by any future public health risks. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our Securities and Exchange Commission ("SEC") filings which are available on the SEC's website at , including in Citius Pharma's Annual Report on Form 10-K for the year ended September 30, 2023, filed with the SEC on December 29, 2023, Citius Oncology's Current Report on Form 8-K, filed with the Commission on August 16, 2024 (as amended by Amendment No. 1 to Form 8-K, filed on August 26, 2024), both as updated by our subsequent filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof, and we expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law. Investor Relations for Citius Pharmaceuticals: Investor Contact: Ilanit Allen [email protected] 908-967-6677 x113 Media Contact: STiR-communications Greg Salsburg [email protected] SOURCE Citius Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果免疫疗法临床1期上市批准引进/卖出

2024-09-05

·PRNewswire

Citius Pharmaceuticals to Participate in the H.C. Wainwright 26th Annual Global Investment Conference

CEO Leonard Mazur to present on Tuesday, September 10, 2024, at 9:00 am ET CRANFORD, N.J., Sept. 5, 2024 /PRNewswire/ -- Citius Pharmaceuticals, Inc. ("Citius Pharma" or the "Company") (Nasdaq: CTXR), today announced that Chairman and CEO Leonard Mazur will present and host one-on-one investor meetings at the H.C. Wainwright & Co. 26th Annual Global Investment Conference taking place September 9–11, 2024, in New York City. H.C. Wainwright Conference Details: *Please note that the presentation date and time are subject to change. Participants should refer to the final program agenda for up-to-date information. Recent Business Developments: During his presentation and investor meetings, Mr. Mazur will discuss recent business developments including: FDA Approval of LYMPHIR™ (denileukin diftitox-cxdl), an immunotherapy for the treatment of cutaneous T-cell lymphoma (CTCL); Merger of the Company's subsidiary with TenX Keane to form publicly listed Citius Oncology, Inc. (Nasdaq: CTOR); and, Achieving primary and secondary endpoints in the completed Phase 3 Pivotal Trial of Mino-Lok®, an antibiotic lock solution designed to salvage central venous catheters in patients with catheter-related bloodstream infections. About Citius Pharmaceuticals, Inc. Citius Pharmaceuticals, Inc. (Nasdaq: CTXR) is a biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products. In August 2024, the FDA approved LYMPHIR, a targeted immunotherapy for an initial indication in the treatment of cutaneous T-cell lymphoma. Citius Pharma's late-stage pipeline also includes Mino-Lok®, an antibiotic lock solution to salvage catheters in patients with catheter-related bloodstream infections, and CITI-002 (Halo-Lido), a topical formulation for the relief of hemorrhoids. A Pivotal Phase 3 Trial for Mino-Lok and a Phase 2b trial for Halo-Lido were completed in 2023. Mino-Lok met primary and secondary endpoints of its Phase 3 Trial. Citius is actively engaged with the FDA to outline next steps for both programs. Citius Pharmaceuticals owns approximately 90% of Citius Oncology. For more information, please visit . Investor Contact: Ilanit Allen [email protected] 908-967-6677 x113 SOURCE Citius Pharmaceuticals, Inc.

临床3期临床2期免疫疗法上市批准临床结果

2024-09-05

·PRNewswire

Citius Pharmaceuticals, Inc. and Citius Oncology, Inc. Announce LYMPHIR™ (Denileukin Diftitox-cxdl) Added to National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology

CRANFORD, N.J., Sept. 5, 2024 /PRNewswire/ -- 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). Continue Reading Citius Oncology logo Lymphir (denileukin diftitox-cxdl) logo 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 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. 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 . 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™ which will be available in the next few days. About Citius Oncology, Inc. Citius Oncology, Inc. (Nasdaq: CTOR) is a platform to develop and commercialize novel targeted oncology therapies. In August 2024, its primary asset, LYMPHIR, was approved by the FDA for the treatment of adults with relapsed or refractory CTCL who had had at least one prior systemic therapy. Management estimates the initial market for LYMPHIR currently exceeds $400 million, is growing, and is underserved by existing therapies. Robust intellectual property protections that span orphan drug designation, complex technology, trade secrets and pending patents for immuno-oncology use as a combination therapy with checkpoint inhibitors would further support Citius Oncology's competitive positioning. Citius Pharmaceuticals owns approximately 90% of Citius Oncology. For more information, please visit . About Citius Pharmaceuticals, Inc. Citius Pharmaceuticals, Inc. (Nasdaq: CTXR) is a biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products. In August 2024, the FDA approved LYMPHIR, a targeted immunotherapy for an initial indication in the treatment of cutaneous T-cell lymphoma. Citius Pharma's late-stage pipeline also includes Mino-Lok®, an antibiotic lock solution to salvage catheters in patients with catheter-related bloodstream infections, and CITI-002 (Halo-Lido), a topical formulation for the relief of hemorrhoids. A Pivotal Phase 3 Trial for Mino-Lok and a Phase 2b trial for Halo-Lido were completed in 2023. Mino-Lok met primary and secondary endpoints of its Phase 3 Trial. Citius is actively engaged with the FDA to outline next steps for both programs. Citius Pharmaceuticals owns approximately 90% of Citius Oncology. For more information, please visit . Forward-Looking Statements This press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements are made based on our expectations and beliefs concerning future events impacting Citius. You can identify these statements by the fact that they use words such as "will," "anticipate," "estimate," "expect," "plan," "should," and "may" and other words and terms of similar meaning or use of future dates. Forward-looking statements are based on management's current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated, and, unless noted otherwise, that apply to Citius Pharma and Citius Oncology, are: our ability to commercialize LYMPHIR and any of our other product candidates that may be approved by the FDA; our need for substantial additional funds; Citius Pharma's ability to meet Nasdaq's continued listing standards; the estimated markets for our product candidates and the acceptance thereof by any market; the ability of our product candidates to impact the quality of life of our target patient populations; risks relating to the results of research and development activities, including those from our existing and any new pipeline assets; our dependence on third-party suppliers; our ability to procure cGMP commercial-scale supply; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; uncertainties relating to preclinical and clinical testing; the early stage of products under development; market and other conditions; risks related to our growth strategy; patent and intellectual property matters; our ability to identify, acquire, close and integrate product candidates and companies successfully and on a timely basis; government regulation; competition; as well as other risks described in our SEC filings. These risks have been and may be further impacted by any future public health risks. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our Securities and Exchange Commission ("SEC") filings which are available on the SEC's website at , including in our Annual Report on Form 10-K for the year ended September 30, 2023, filed with the SEC on December 29, 2023, and updated by our subsequent filings with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof, and we expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law. Investor Relations for Citius Pharmaceuticals: Investor Contact: Ilanit Allen [email protected] 908-967-6677 x113 Media Contact: STiR-communications Greg Salsburg [email protected] SOURCE Citius Pharmaceuticals, Inc.