A Randomized International Phase 3 Trial of Imatinib and Chemotherapy With or Without Blinatumomab in Patients With Newly-Diagnosed Philadelphia Chromosome-Positive or Philadelphia Chromosome-Like ABL-Class B-Cell Acute Lymphoblastic Leukemia

This phase III trial compares the effect of the combination of blinatumomab with dasatinib and standard chemotherapy versus dasatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (PH+) or Philadelphia chromosome-like (Ph-Like) ABL-class B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib in combination with standard chemotherapy may work better in treating patients with PH+ or Ph-Like ABL-class B-ALL compared to dasatinib and chemotherapy alone.

Start Date28 Feb 2025

Sponsor / Collaborator

National Cancer Institute

NCT06317662 / Not yet recruitingPhase 2IIT

A Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax

This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged [R]) or without a KMT2A gene rearrangement (KMT2A-germline [G]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.

Start Date26 Jan 2025

Sponsor / Collaborator

National Cancer Institute

NCT06624670 / Not yet recruitingPhase 3

A Multi-centre, Randomised, Placebo-controlled, Double-blind, Parallel-group Trial to Evaluate Safety and Efficacy of Spesolimab (BI 655130) in Adult Patients With Ulcerative Pyoderma Gangrenosum (PG) Who Require Systemic Therapy

The purpose of this study is to find out whether a medicine called spesolimab helps people with pyoderma gangrenosum (PG). The main aim is to see whether spesolimab leads to closure of PG ulcers. This study is open to adults with ulcerative PG with at least 1 ulcer that measures between 5 cm^2 to 80 cm^2 in size.
This study has 2 parts. In Part 1, participants are put into groups randomly, which means by chance. 1 group gets spesolimab and the other group gets placebo. Placebo injections look like spesolimab injections, but do not contain any medicine. Every participant has a 2 in 3 chance of getting spesolimab. For the first 8 weeks, participants also take corticosteroid medicine by mouth.
In Part 2, participants are put into groups again. Participants without open ulcers have an equal chance of getting spesolimab or placebo. Participants with open skin ulcers will get spesolimab.
In both parts, participants receive spesolimab or placebo as an infusion into a vein every 4 weeks.
Participants are in the study for about 1.5 years. During this time, they visit the study site 20 times. At study visits, doctors check the participant's skin for signs of PG. The doctors also regularly check participants' health and take note of any unwanted effects. The results of the groups are compared to see whether the treatment works.

Start Date15 Jan 2025

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with Prednisolone

100 Translational Medicine associated with Prednisolone

100 Patents (Medical) associated with Prednisolone

29,882

Literatures (Medical) associated with Prednisolone

01 Apr 2025·DEN open

Duodenitis associated with ulcerative colitis and pouchitis after total colectomy successfully treated with upadacitinib: A case report

Article

Author: Tezuka, Yukari ; Kojima, Kentaro ; Onishi, Sachiyo ; Shimizu, Masahito ; Masuda, Naoya ; Takada, Jun ; Otani, Kiichi ; Kubota, Masaya ; Ibuka, Takashi

Abstract:

A 27‐year‐old man had ulcerative colitis (UC) 1 year prior and underwent a colectomy and two‐stage ileal pouch‐anal anastomosis for medically refractory UC 6 months ago. He visited our department with epigastric pain and discomfort, increased stool frequency, and bloody diarrhea. Esophagogastroduodenoscopy revealed continuous diffuse friable mucosa, erosions, and edema in the duodenum, and pouchoscopy revealed multiple ulcers and purulent mucus adhesions. Based on endoscopic and pathological findings, the patient was diagnosed with duodenitis associated with UC and pouchitis, for which he received oral prednisolone (40 mg/day) and ciprofloxacin. The frequency of stools and occurrence of bloody diarrhea reduced, and epigastric pain and discomfort improved after 2 weeks. However, when prednisolone was discontinued, the symptoms worsened, albumin level decreased, and C‐reactive protein level increased. Following this, we administered a 20 mg prednisolone sodium phosphate enema once daily, and the patient's symptoms improved. However, the symptoms relapsed when the enema was discontinued. Assuming that the patient had steroid‐dependent duodenitis associated with UC and pouchitis, we initiated upadacitinib. His symptoms improved within a few days, and biomarkers returned to normal after 1 month. Nine months after initiating the upadacitinib treatment, endoscopic remission was achieved in the mucosa of the duodenum and pouch. The patient has been in clinical remission for 1 year without any adverse events.

01 Apr 2025·DEN open

Steroid lifting method during endoscopic submucosal dissection: A novel strategy for stricture prevention

Article

Author: Baldaque‐Silva, Francisco ; Maltzman, Henrik ; Omae, Masami ; Vujasinovic, Miroslav ; Wang, Naining

Abstract:

A 73‐year‐old male patient was referred to us with a long Barrett's esophagus (BE). He had a history of pulmonary embolism under anticoagulant therapy. Esophagogastroduodenoscopy showed a C8M9 BE with no macroscopic lesions. Random biopsies from the BE revealed multifocal high‐grade dysplasia. The case was discussed in a multidisciplinary team conference and the decision for full resection of BE with endoscopic submucosal dissection (ESD) was made. Considering the large ESD resection and the high risk of stricture, we developed a novel preventive technique: the “steroid lifting method” for submucosal injection during ESD. Complete circumferential ESD with en bloc resection was performed using the “steroid lifting method”, without adverse events. Oral liquids were initiated on day 1 and the patient was discharged on day 4. Oral prednisolone (30 mg per day) was started and tapered for a total of 6 weeks. The pathological examination confirmed multifocal high‐grade dysplasia, with radical and curative resection. The patient had neither stricture, dysphagia nor recurrence of Barrett's mucosa at the 2, 6, 12, and 24‐month follow‐up. International guidelines recommend oral prednisolone and triamcinolone injection to prevent stricture formation in large ESD of esophageal squamous cell carcinoma. However, there is no solid data on BE ESD. The risk factors for stricture formation and the optimal preventive management after large BE ESD is not known. The “steroid lifting method” might be an option in this context. Large prospective studies addressing stricture formation and preventive measures on BE ESD are necessary.

01 Jan 2025·JOURNAL OF ETHNOPHARMACOLOGY

Evaluation of Anti-arthritic and in-vitro Anti-inflammatory activity of Vaisvanara Churna

Article

Author: Gaidhani, Sudesh N. ; Ilavarasan, R. ; Manikandan, N ; Kusuma, G ; Ilavarasan, R ; Thenmozhi, M. ; Gaidhani, Sudesh N ; Kusuma, G. ; Arunadevi, R ; Arunadevi, R. ; Thenmozhi, M ; Manikandan, N.

ETHNOPHARMACOLOGICAL RELEVANCE:

Vaisvanara Churna used traditionally for the treatment of Amavata (Rheumatoid arthritis), Shotaprasamana (Anti-inflammatory) and as Saraka (Laxative).

AIM:

Aim of the study is to evaluate anti arthritic activity and in vitro anti-inflammatory potential of Vaisvanara Churna in experimental animals.

MATERIALS AND METHODS:

In-vitro anti-inflammatory activity of aqueous extract of Vaisvanara Churna (100-500 μg/ml) was evaluated by using membrane stabilization methods. Anti arthritic activity was evaluated by using 0.1 ml of Complete Freund's Adjuvant (CFA) injected into sub plantar surface of left hind paw of each wistar rat on day 1 followed by treatment with Vaisvanara Churna at various dose levels (450, 900, and 1800 mg/kg b.w) and standard drug Prednisolone (5 mg/kg) for 21 days. The following parameters namely change in the body weight of animals, paw volume, ankle joint thickness were measured at 0, 3, 8, 17 & 21 day intervals and radiographic changes were assessed. In addition to this, response to painful stimuli by application of forced pressure was measured by using Pressure Application Measurement (PAM) method.

RESULTS:

In-vitro anti-inflammatory activity Vaisvanara Churna exhibited dose dependent membrane stabilizing activity. Treatment with Vaisvanara Churna showed significant (p < 0.05) inhibition of paw edema, reduction in ankle joint thickness and increase in the body weight of wistar albino rats was observed. There is a significant increase (p < 0.001) in the latency of limb withdrawal response, reduction in the organ indices (spleen and thymus) were noted.

CONCLUSION:

This study demonstrates that Vaisvanara Churna possesses in vitro anti inflammatory and anti-arthritic potential and supports its folklore use in the treatment of arthritis.

147

News (Medical) associated with Prednisolone

23 Sep 2024

·www.businesswire.com

Datopotamab deruxtecan final overall survival results reported in patients with metastatic HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 Phase III trial

WILMINGTON, Del.--( BUSINESS WIRE )--High-level results from the TROPION-Breast01 Phase III trial of datopotamab deruxtecan (Dato-DXd) compared to investigator’s choice of chemotherapy, which previously met the dual primary endpoint of progression-free survival (PFS), did not achieve statistical significance in the final overall survival (OS) analysis in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. This analysis follows positive PFS results presented at the 2023 European Society for Medical Oncology Congress which showed datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement in PFS. An improvement in patient-reported outcomes was also seen. 1 The PFS data and additional results for key secondary endpoints were published this month in the Journal of Clinical Oncology. The safety profile of datopotamab deruxtecan was consistent with that observed in the previous analysis including lower rates of Grade 3 or higher treatment-related adverse events compared to chemotherapy, and no new safety concerns identified. All grade interstitial lung disease (ILD) rates remained low with no new Grade 3 or higher ILD events observed. With multiple antibody drug conjugates (ADCs) approved during the course of the trial, including ENHERTU ® (fam-trastuzumab deruxtecan-nxki), subsequent treatment following patients’ disease progression or treatment discontinuation is likely to have affected survival results. Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “ The metastatic HR-positive breast cancer treatment landscape has advanced remarkably in the last several years to benefit patients. Based on the TROPION-Breast01 results, there is evidence of the clinical value of datopotamab deruxtecan in this setting. We will continue discussions with regulatory authorities and apply insights from these results to our clinical development program for datopotamab deruxtecan in breast cancer.” Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “ Datopotamab deruxtecan has previously shown a statistically significant progression-free survival benefit in TROPION-Breast01, a result supported by multiple meaningful secondary measures including patient-reported outcomes. We are proud to have brought forth a new standard of care for patients with metastatic breast cancer with ENHERTU and we remain committed to making datopotamab deruxtecan another potential option for patients who can benefit.” Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd ADC discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo. The data will be presented at a forthcoming medical meeting and shared with regulatory authorities currently reviewing applications for this indication. In addition to TROPION-Breast01, AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan alone and with immunotherapy as treatment for patients with triple-negative or HR-low, HER2-negative breast cancers in the TROPION-Breast02 , TROPION-Breast03 , TROPION-Breast04 and TROPION-Breast05 Phase III trials. IMPORTANT SAFETY INFORMATION Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either: In the metastatic setting, or In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen Unresectable or metastatic HER2-positive (IHC3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms. Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception. Contraindications None. Warnings and Precautions Interstitial Lung Disease / Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. HER2-Positive or HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 1.0% of patients treated with ENHERTU. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21). Neutropenia Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 10 9 /L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 10 9 /L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by one level. For febrile neutropenia (ANC <1.0 x 10 9 /L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by one level. HER2-Positive or HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 63% of patients. Seventeen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1% of patients. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients. Left Ventricular Dysfunction Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment. HER2-Positive or HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 3.8% of patients, of which 0.6% were Grade 3. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Embryo-Fetal Toxicity ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU. Additional Dose Modifications Thrombocytopenia For Grade 3 thrombocytopenia (platelets <50 to 25 x 10 9 /L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 10 9 /L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by one level. Adverse Reactions HER2-Positive and HER2-Low Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 1799 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 65% were exposed for >6 months and 38% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (73%), decreased white blood cell count (70%), decreased hemoglobin (66%), decreased neutrophil count (63%), decreased lymphocyte count (58%), fatigue (56%), decreased platelet count (48%), increased aspartate aminotransferase (47%), increased alanine aminotransferase (43%), vomiting (40%), increased blood alkaline phosphatase (38%), alopecia (34%), constipation (33%), decreased appetite (32%), decreased blood potassium (31%), diarrhea (29%), musculoskeletal pain (24%), and abdominal pain (20%). HER2-Positive Metastatic Breast Cancer DESTINY-Breast03 The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg intravenously once every three weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30). Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, interstitial lung disease, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (one patient each). ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), decreased blood potassium (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%). HER2-Low Metastatic Breast Cancer DESTINY-Breast04 The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU. Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each). ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and decreased blood potassium (25%). HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg) DESTINY-Lung02 evaluated two dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis. The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every three weeks until disease progression or unacceptable toxicity in DESTINY‑Lung02. Nineteen percent of patients were exposed for >6 months. Serious adverse reactions occurred in 30% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin I. Fatality occurred in 1 patient with suspected ILD/pneumonitis (1%). ENHERTU was permanently discontinued in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, diarrhea, decreased blood potassium, hypomagnesemia, myocarditis, and vomiting. Dose interruptions of ENHERTU due to adverse reactions occurred in 23% of patients. Adverse reactions which required dose interruption (>2%) included neutropenia and ILD/pneumonitis. Dose reductions due to an adverse reaction occurred in 11% of patients. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (61%), decreased white blood cell count (60%), decreased hemoglobin (58%), decreased neutrophil count (52%), decreased lymphocyte count (43%), decreased platelet count (40%), decreased albumin (39%), increased aspartate aminotransferase (35%), increased alanine aminotransferase (34%), fatigue (32%), constipation (31%), decreased appetite (30%), vomiting (26%), increased alkaline phosphatase (22%), and alopecia (21%). HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least one dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m 2 biweekly or paclitaxel (N=7) 80 mg/m 2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU. Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in one patient each (0.8%). ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and decreased blood potassium. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%). HER2-Positive (IHC3+) Unresectable or Metastatic Solid Tumors The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2). Serious adverse reactions occurred in 34% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney injury, anemia, cellulitis, and dyspnea. Fatalities due to adverse reactions occurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in one patient each (0.3%): acute kidney injury, cerebrovascular accident, general physical health deterioration, pneumonia, and hemorrhagic shock. ENHERTU was permanently discontinued in 15% of patients, of which ILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions occurred in 48% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count, anemia, COVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis. Dose reductions occurred in 27% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (75%), nausea (69%), decreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%), decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite (34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%), constipation (28%), decreased sodium (22%), stomatitis (20%), and upper respiratory tract infection (20%). Use in Specific Populations Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU. Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose. Females and Males of Reproductive Potential: Pregnancy testing : Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception : Females : ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males : Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility : ENHERTU may impair male reproductive function and fertility. Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients. Geriatric Use: Of the 1287 patients with HER2-positive or HER2-low breast cancer treated with ENHERTU 5.4 mg/kg, 22% were ≥65 years and 3.8% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (59%) as compared to younger patients (49%). Of the 101 patients with HER2-mutant unresectable or metastatic NSCLC treated with ENHERTU 5.4 mg/kg, 40% were ≥65 years and 8% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 192 patients with HER2-positive (IHC 3+) unresectable or metastatic solid tumors treated with ENHERTU 5.4 mg/kg in DESTINY-PanTumor02, DESTINY-Lung01, or DESTINY-CRC02, 39% were 65 years or older and 9% were 75 years or older. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min). Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST). To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch. Please see accompanying full Prescribing Information , including Boxed WARNINGS, and Medication Guide . Notes HR-positive breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 2 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000 deaths globally. 2 While survival rates are high for those diagnosed with early breast cancer, less than 35% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis. 3 Approximately 70% of diagnosed cases are considered what has been historically called HR-positive, HER2-negative breast cancer (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-). 3 Endocrine therapies are widely given consecutively in the early lines of treatment for HR-positive metastatic breast cancer; however, after two lines of treatment, further efficacy from endocrine therapy is often limited. 4 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes. 4-7 TROP2 is a protein broadly expressed in HR-positive, HER2-negative breast cancer and is associated with increased tumor progression and poor survival. 8,9 TROPION-Breast01 TROPION-Breast01 is a global, randomized, multicenter, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in adult patients with unresectable or metastatic HR-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease. Following disease progression or discontinuation of datopotamab deruxtecan or chemotherapy, patients had the option to receive subsequent treatment at the discretion of their physician. Crossover between trial arms was not permitted. The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov . Datopotamab deruxtecan (Dato-DXd) Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer (TNBC) and HR-positive, HER2-negative breast cancer. The program includes seven Phase III trials in lung cancer and five Phase III trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialize fam-trastuzumab deruxtecan-nxki in March 2019 and datopotamab deruxtecan in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan. AstraZeneca in breast cancer Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumor environment. With fam-trastuzumab deruxtecan-nxki, a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines goserelin and aims to reshape the HR-positive space with first-in-class AKT inhibitor, capivasertib, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting. PARP inhibitor olaparib is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research olaparib in these settings and to explore its potential in earlier disease. To bring much-needed treatment options to patients with TNBC, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy durvalumab, capivasertib in combination with chemotherapy, and durvalumab in combination with other oncology medicines, including olaparib and fam-trastuzumab deruxtecan-nxki. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. About AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca . References Pernas S, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer: Patient-reported outcomes (PROs) from the TROPION-Breast01 study. Presented at: ASCO Congress 2024; 31 May - 4 June, 2024; Chicago, IL. Abstract 1006. Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 Apr 4. doi: 10.3322/caac.21834. National Cancer Institute. Surveillance, Epidemiology and End Results Program. Available at: https://seer.cancer.gov/statfacts/html/breast-subtypes.html . Accessed August 2024 Manohar P, et al. Updates in endocrine therapy for metastatic breast cancer. Cancer Biol Med . 2022 Feb 15; 19(2):202–212. Cortes J, et al. Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377:914-923. Yuan P, et al. Eribulin mesilate versus vinorelbine in women with locally recurrent or metastatic breast cancer: A randomised clinical trial. Eur J Cancer . 2019;112:57–65. Jerusalem G, et al. Everolimus Plus Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen Receptor–Positive, HER2-Negative Advanced Breast Cancer. JAMA Oncol . 2018;4(10):1367–1374. Goldenberg D, et al. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget. 2018;9(48): 28989-29006. Vidula N, et al. Trophoblast Cell Surface Antigen 2 gene (TACSTD2) expression in primary breast cancer. Breast Cancer Res Treat . 2022 Aug;194(3):569-575. US-93959 Last Updated 9/24

Clinical ResultPhase 3Accelerated ApprovalADCImmunotherapy

19 Sep 2024

·www.prnewswire.com

Elanco Announces FDA Approval and Launch of Zenrelia™ (ilunocitinib tablets), Offering An Effective, Safe Solution in Canine Dermatology

U.S. Food and Drug Administration approves Zenrelia, a once-daily oral JAK inhibitor for dogs with allergic and atopic dermatitis Elanco enters the estimated $1.7 billion global canine dermatology market, highly accretive to existing portfolio In a head-to-head study, Zenrelia was shown to be at least as effective as the market incumbent JAK inhibitor at the primary end point, with an additional endpoint at which Zenrelia got 77% of dogs to clinical remission of itch, compared to 53% of dogs treated with Apoquel® (oclacitinib tablet)1* Zenrelia launch begins in U.S. with Elanco now taking orders; product expected to ship in coming days GREENFIELD, Ind., Sept. 19, 2024 /PRNewswire/ -- Elanco Animal Health Incorporated (NYSE: ELAN) today announced the U.S. Food and Drug Administration (FDA) has approved Zenrelia™, a safe, highly effective, and convenient once-daily oral JAK inhibitor for control of pruritus (itching) associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age. Elanco announces FDA approval and launch of Zenrelia™ (ilunocitinib tablets), offering an effective, safe solution in canine dermatology; unlocks new solution to treat 17 million itchy dogs with just one daily dose Elanco conducted a head-to-head noninferiority study comparing the efficacy and safety of Zenrelia and Apoquel for submission in the European Union. Itching is one of the top reasons pet owners bring their dog to the veterinarian, and pet owners and veterinarians want more canine dermatology options. Approximately 17 million dogs suffer from allergic skin disease, including atopic dermatitis, food allergies or flea sensitivity2. Among pet owners who say their dog's itch is not under control, 60% say they've tried treating the itch, but nothing works.3 The approval of Zenrelia represents an important advancement in treating itchy dogs suffering from chronic, acute or seasonal itch and inflammation in a single, once daily tablet from the start. Zenrelia targets itch where it starts by blocking the pathways involved in allergic itch to break the itch-scratch cycle.4 Zenrelia offers visible improvement from the first dose and minimizes the risk of "rebound itch" which affects many dogs treated with the competitive JAK inhibitor.5-10 "Today is a historic day for Elanco with our first of several expected entries into the fast-growing global canine dermatology market, bringing veterinarians and pet owners a highly effective new solution that got more dogs back to normal levels of itch in a head-to-head study with the current JAK inhibitor on the market1*," said Jeff Simmons, President and CEO, Elanco Animal Health. "We are excited to offer veterinarians and pet owners a solution that can relieve the burdens of itch, while also becoming just the second animal health company to offer veterinarians a comprehensive portfolio, including parasiticides, vaccines, pain and other therapeutics, and now, dermatology." Promising Results from a Head-to-Head Study1 Elanco conducted a head-to-head noninferiority study comparing the efficacy and safety of Zenrelia and Apoquel for submission in the European Union. The randomized, double-blind study of 338 client-owned dogs with confirmed atopic dermatitis was conducted across 25 study sites in four countries. The study shows one daily dose of Zenrelia is at least as effective as the market incumbent JAK inhibitor at the primary end point on Day 28. Additionally, there were several promising additional endpoints*: Zenrelia provided consistently greater relief from itch and skin lesions over time, with once-daily dosing from the start while rebound itch was observed in Apoquel treated dogs after dosing decreased to once daily after Day 14. Zenrelia got more dogs back to normal levels of itch by the end of the study, with 77% of Zenrelia treated dogs achieving clinical remission of itch, compared to 53% of Apoquel treated dogs. The difference in treatment response was recognized by owners and veterinarians, with both groups rating Zenrelia higher than Apoquel for overall response to treatment from Day 28 through to Day 112. The adverse event profile was similar between the Zenrelia and Apoquel groups. Veterinarians And Pet Owners Need More Options Research shows that nearly 70% of veterinarians would be willing to stock another dermatology product2 as there are still too many dogs that aren't getting itch relief and many pet owners that would benefit from a more affordable option. "We're dedicated to solving these unmet needs in canine dermatology," said Bobby Modi, Executive Vice President, U.S. Pet Health and Global Digital Transformation. "Zenrelia's once-daily dosing is more convenient and will be affordable for pet owners with the launch list price about 20% less for nearly all dogs compared to the current JAK inhibitor. Pet owners will appreciate even greater savings in the first 14 days for Zenrelia given its single vs. twice daily dosing. Very importantly, Zenrelia minimizes the opportunity for rebound itch given its consistent once daily dosing compared to the market incumbent."1, 5-10* Take for example, Trooper, a one-year-old Yorkshire Terrier who enrolled in the Zenrelia clinical trial. Prior to participating in the clinical trial, Trooper's itch level was 10 out of 10 on the pruritus visual analog scale (PVAS), a validated observation scale for canine itch. By the end of the first two weeks of treatment, he was back to a normal itch level of 1.9 and finished the clinical trial with an itch level of 1.1.** A PVAS score of less than 2 is considered a normal level of itch, also referred to as clinical remission of itch. You can read more about Trooper's story here. "I was excited to participate as a clinical investigator in the Zenrelia field study because it is clear we need more treatment options for itchy dogs," said Dr. Tom Lewis, veterinarian and founder of Dermatology for Animals, a group of veterinary dermatology clinics committed to caring for pets with allergies. "I saw amazing results during the clinical field study and am eager to get many patients started on Zenrelia. Watching dogs get back to normal quickly and seeing the bond restored between the dog and pet parent was incredibly rewarding." Demonstrated Safety The safety of Zenrelia has been demonstrated in multiple toxicity and clinical safety studies. The required margin of safety study for Zenrelia was conducted in healthy dogs dosed with placebo, 1, 2, 3 or 5 times the label dose daily for six months. All dogs completed the study with no serious adverse events. The Zenrelia label includes a boxed warning on safety related to concurrent vaccine administration based on the results of a vaccine response study. In this study, eight, 10-month-old laboratory beagles received primary vaccinations while being treated with Zenrelia at 3X the label dose. Two dogs were immunosuppressed and euthanized during the study. Antibody responses were evaluated following vaccination. All but one dog responded successfully to modified live vaccines, and two of six dogs responded to inactivated Rabies vaccine at the primary endpoint. Dogs should be up to date on vaccinations prior to starting Zenrelia. It's important for veterinarians to read the entire package insert, including the Boxed Warning, before prescribing Zenrelia. "Zenrelia has been demonstrated to be safe and highly effective in a number of studies," said Dr. Mara Tugel, veterinarian and Dermatology Medical Strategic Lead at Elanco. "We recognize that veterinarians need clinically relevant data to guide treatment choices, and plan to pursue additional studies to evaluate vaccine response in Zenrelia-treated dogs. We will continue to work to improve the label over time." Veterinarians in the U.S. can learn more and place orders for Zenrelia now at Zenreliaforvets.com. Orders are expected to begin shipping in the coming days. Elanco will conduct a conference call on Friday, September 20, 2024 at 8:00 am eastern time to discuss the Zenrelia approval with the investment community and other interested parties. A live webcast of the conference call can be accessed through the link that will be posted on Elanco's website at . A replay will also be available on the website shortly following the call. ABOUT ELANCO Elanco Animal Health Incorporated (NYSE: ELAN) is a global leader in animal health dedicated to innovating and delivering products and services to prevent and treat disease in farm animals and pets, creating value for farmers, pet owners, veterinarians, stakeholders and society as a whole. With nearly 70 years of animal health heritage, we are committed to helping our customers improve the health of animals in their care, while also making a meaningful impact on our local and global communities. At Elanco, we are driven by our vision of Food and Companionship Enriching Life and our Elanco Healthy Purpose™ sustainability pillars – all to advance the health of animals, people, the planet and our enterprise. Learn more at . INDICATIONS is indicated for control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age. IMPORTANT SAFETY INFORMATION Read the entire package insert before using this drug, including the boxed warning. For Full prescribing information call 1 888 545 5973 or visit . WARNING: VACCINE-INDUCED DISEASE AND INADEQUATE IMMUNE RESPONSE TO VACCINES. Based on results of the vaccine response study, dogs receiving Zenrelia are at risk of fatal vaccine-induced disease and inadequate immune response to vaccines. Discontinue Zenrelia for at least 28 days to 3 months prior to vaccination and withhold Zenrelia for at least 28 days after vaccination. Dogs should be up to date on vaccinations prior to starting Zenrelia. Do not use in dogs less than 12 months old or dogs with a serious infection. Monitor dogs for infections because Zenrelia may increase susceptibility to opportunistic infections. Neoplastic conditions (benign and malignant) were observed during clinical studies. Consider the risks and benefits of treatment in dogs with a history of recurrence of these conditions. The most common adverse reactions were vomiting, diarrhea and lethargy. Zenrelia has not been evaluated in breeding, pregnant, or lactating dogs and concurrent use with glucocorticoids, cyclosporine, or other systemic immunosuppressive agents has not been tested. For full prescribing information see package insert. Forward-Looking Statements: TBD Zenrelia, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates. Apoquel is a trademark of Zoetis Services, LLC. © 2024 Elanco or its affiliates. Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of the federal securities laws, including, without limitation, statements concerning Zenrelia as a treatment for dogs with allergic dermatitis and timeline for launch, commercial uptake, as well as future studies, publications and other milestones related to Zenrelia, and reflects Elanco's current beliefs and expectations. However, as with any animal health pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, that future studies will receive regulatory approval, or that Elanco will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Elanco's expectations, see Elanco's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Elanco undertakes no duty to update forward-looking statements to reflect events after the date of this release. Investor Contact: Katy Grissom (317) 273-9284 [email protected] Media Contact: Season Solorio (765) 316-0233 [email protected]   References: Elanco Animal Health. Data on File. AVMA Sourcebook. Elanco, Dermatology Products SOV Study, 2023 Elanco and FleishmanHillard TRUE Global Intelligence Survey. Elanco Animal Health. Data on File. Cosgrove SB, et al. A blinded, randomized, placebo-controlled trial of efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel®) in client-owned dogs with atopic dermatitis. Vet Dermatol, 2013; 24: 587-e142. Little PR, et al. A blinded, randomized clinical trial comparing the efficacy and safety of oclacitinib and ciclosporin for the control of atopic dermatitis in client-owned dogs. Vet Dermatol, 2015; 26: 23-e8. Fukuyama T, et al. Demonstration of rebound phenomenon following abrupt withdrawal of the JAK1 inhibitor oclacitinib. European Journal of Pharmacology, 2017; 794: 20-26. Takahashi J, et al. Efficacy and safety of 0.0584% hydrocortisone aceponate topical spray and systemic oclacitinib combination therapy in dogs with atopic dermatitis: a randomized, double-blinded, placebo-controlled trial. Vet Dermatol, 2021; 32: 119-e35. Denti D, et al. Prolonged twice-daily administration of oclacitinib for the control of canine atopic dermatitis: a retrospective study of 53 client-owned atopic dogs. Vet Dermatol, 2022; 33: 149-e42. Olivry T, et al. A randomized controlled trial testing the rebound-preventing benefit of four days of prednisolone during the induction of oclacitinib therapy in dogs with atopic dermatitis. Vet Dermatol, 2023; 34: 99-106. *Zenrelia was as effective as Apoquel at the primary study endpoint (Day 28). Additional outcomes (P≤0.05) included: proportion of dogs achieving PVAS <2; Mean PVAS and CADESI-4 scores, and veterinary and owner assessments of overall response to treatment. Additional endpoint P values are not adjusted for multiple testing; therefore, caution should be exercised in interpretation. ** Individual results may vary. In the U.S. Allergic Dermatitis and Atopic Dermatitis field studies, the proportion of treated dogs achieving normal itch levels (PVAS <2) after 14 days was 38.4% and 32.8%, respectively. SOURCE Elanco Animal Health WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultDrug ApprovalVaccineClinical Study

19 Sep 2024

·www.businesswire.com

Sparrow Pharmaceuticals Presented New Data on Clofutriben and Prednisolone for Polymyalgia Rheumatica Treatment at DGRh Kongress 2024

PORTLAND, Ore.--( BUSINESS WIRE )-- Sparrow Pharmaceuticals today announced that it presented new data from its ongoing Phase 2 clinical trial of its HSD-1 inhibitor, clofutriben (referred to SPI-62 in the study), in combination with prednisolone for the treatment of polymyalgia rheumatica (PMR) at the German Congress of Rheumatology (DGRh Kongress 2024) in Dusseldorf, Germany on 18 – 21 September, 2024. The data was presented in an oral presentation that took place on Thursday, September 19 th at 3:25PM CEST and a poster session. David Katz, PhD, Chief Scientific Officer at Sparrow discussed the abstract titled “ An 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor to Optimize the Effects of Prednisolone in Patients with Polymyalgia Rheumatica (PMR) .” Key findings were highlighted from the trial, which investigated the potential of clofutriben to reduce or prevent side effects of prednisolone while maintaining its effectiveness in PMR patients. The trial included 40 participants with confirmed PMR who were given prednisolone 10 mg, 15 mg, or 20 mg together with clofutriben 6 mg for 2 weeks. Patients also were given prednisolone 10 mg with placebo for clofutriben for 2 weeks. Result highlights are: No PMR relapses occurred when prednisolone 15 mg or 20 mg was co-administered with clofutriben. A combination of prednisolone 20 mg with clofutriben showed similar efficacy as prednisolone 10 mg with placebo, based on analysis of participants’ symptoms, physical function, and biomarkers of inflammation. All prednisolone doses in combination with clofutriben showed less glucocorticoid toxicity compared to prednisolone with placebo. "The data suggest that by using an HSD-1 inhibitor like clofutriben, we may be able to improve the balance between the therapeutic benefits and side effects of glucocorticoid therapy in patients with PMR," said Dr. Katz. "These encouraging findings support Sparrow’s innovative approach to develop treatments that may spare patients from the negative effects of glucocorticoid use, while maintaining the therapeutic benefits. This could potentially offer a new treatment paradigm for patients with rheumatic diseases and the many other conditions treated with glucocorticoids." Additionally, Sparrow has expanded its PROST! Phase 2 clinical trial ( NCT05436652 ) with a fifth cohort to explore clofutriben in combination with prednisolone for the treatment of PMR. This will allow for the continued study of how clofutriben can maintain the efficacy of steroid medicines without the harsh side effects. To learn more about Sparrow Pharmaceuticals and clofutriben (SPI-62), visit www.sparrowpharma.com . About Sparrow Pharmaceuticals Sparrow Pharmaceuticals was founded to spare patients the ravages of steroids. Leveraging underappreciated scientific insights into glucocorticoid biology, the company is working to provide better treatment options for serious disorders of hypercortisolism, and to revolutionize the treatment of autoimmune and inflammatory conditions. Its lead product, clofutriben (SPI-62), is an oral, small molecule, novel therapeutic treatment designed to target a source of active intracellular glucocorticoids in key tissues.

Clinical ResultPhase 2

100 Deals associated with Prednisolone

External Link

KEGG	Wiki	ATC	Drug Bank
D00472	Prednisolone	D07XA02 D07AA03 S02BA03	DB00860

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Mucocutaneous Lymph Node Syndrome	JP	Shionogi Pharma Co., Ltd.	13 Sep 2013
Multiple Myeloma	JP	Shionogi Pharma Co., Ltd.	16 Sep 2011
Preeclamptic Toxemia	JP	Shionogi Pharma Co., Ltd.	23 Jul 1985
Eczema	JP	Tatsumi Kagaku Co., Ltd.	01 Jul 1967
Adrenal Insufficiency	US	Pharmacia & Upjohn, Inc.	21 Jun 1955
Arthritis	US	Pharmacia & Upjohn, Inc.	21 Jun 1955
Celiac Disease	US	Pharmacia & Upjohn, Inc.	21 Jun 1955
Colitis, Ulcerative	US	Pharmacia & Upjohn, Inc.	21 Jun 1955
Insulin Resistance	US	Pharmacia & Upjohn, Inc.	21 Jun 1955
Leukemia	US	Pharmacia & Upjohn, Inc.	21 Jun 1955
Lymphoma	US	Pharmacia & Upjohn, Inc.	21 Jun 1955
Systemic Lupus Erythematosus	US	Pharmacia & Upjohn, Inc.	21 Jun 1955
Autoimmune Diseases	CN	Tianjin Jinjin Pharmaceutical Co. Ltd.	-

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cutaneous hypersensitivity	Phase 3	BR	EMS SA (Brazil)	01 Feb 2014
Exanthema	Phase 3	BR	EMS SA (Brazil)	01 Feb 2014
Rhinitis, Allergic	Phase 3	BR	EMS SA (Brazil)	01 Oct 2013
Advanced Prostate Carcinoma	Phase 2	KR	Janssen Research & Development LLC	30 Aug 2011
Advanced Prostate Carcinoma	Phase 2	TW	Janssen Research & Development LLC	30 Aug 2011
Rheumatoid Arthritis	Phase 2	AU	GSK Plc	21 Jun 2005
Rheumatoid Arthritis	Phase 2	FR	GSK Plc	21 Jun 2005
Rheumatoid Arthritis	Phase 2	DE	GSK Plc	21 Jun 2005
Rheumatoid Arthritis	Phase 2	RU	GSK Plc	21 Jun 2005
Rheumatoid Arthritis	Phase 2	GB	GSK Plc	21 Jun 2005

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03792256 (CTgov)	Phase 1	Recurrent Adult Acute Lymphoblastic Leukemia \| T-Cell Lymphoma \| acute leukemia ... View more	12	ARAC (Stratum 1 With 50 mg/m^2)	clothutqbq(pojtlsijxs) = ppagynqcqc ftlomgcfhm (ddujdnwulk, fiafjmyosc - cqnbocgjmd) View more	-	16 Aug 2024
				ARAC (Stratum PK With 50 mg/m^2)	clothutqbq(pojtlsijxs) = azdrbskdzc ftlomgcfhm (ddujdnwulk, hgoxoleqmr - qnsjrvhbfp) View more
NCT05768282 (Pubmed) Manual	Phase 4	Esophageal Carcinoma	48	Oral prednisolone	yasevcyhmr(mdbebjtksg) = gzqwxttgmh mlfhavwnuj (pziphherwy ) View more	Positive	05 Apr 2024
NCT00945724 (IELSG30, Pubmed) Manual	Phase 2	Diffuse Large B-Cell Lymphoma First line	54	R-CHOP regimen + liposomal cytarabine+ methotrexate	mghbelndwo(klydqgbkbf) = bcjkvhheyy olryjhijuq (cevofykjue, 81 - 97) View more	Positive	26 Mar 2024
NCT02162810 (CTgov)	Not Applicable	Hypospadias	28	Prednisolone (Oral Steroids)	driwiaickm(mbskkstdxi) = bggjypluuc rnlhxriksh (thishtsddu, omxxzjktyt - fyvrslzdyr) View more	-	22 Dec 2023
				placebo-controlled (Placebo-controlled)	driwiaickm(mbskkstdxi) = ykfjnmmpkn rnlhxriksh (thishtsddu, wziuydxlls - nthmmhvroz) View more
ACR2023	Not Applicable	Polymyalgia Rheumatica	-	Prednisolone	olsqcgggia(bjafyhtgmy) = fufgkvqgmd skeyzcnkma (gndsrrxrpi ) View more	-	14 Nov 2023
NCT02585258 (Gloria, CTgov)	Phase 4	Rheumatoid Arthritis	451	Prednisolone (Prednisolone)	jukynoqhmr(reorbfblne) = rwrebjhgfu qdkxtprnol (ksvgckvspz, vrrnfkzeyg - wbftabsfee) View more	-	18 Jul 2023
				Placebo (Placebo)	jukynoqhmr(reorbfblne) = kukatfgzxc qdkxtprnol (ksvgckvspz, qcyphpvcwj - iiapxfaohh) View more
BFM 2009 (EHA2023)	Not Applicable	Acute Lymphoblastic Leukemia	74	Dexamethasone	ouxzgfzokg(ylugeqevxr) = Dexa group had higher incidence of lymphopenia lfrrbvfnvt (tlwmfaescl ) View more	-	08 Jun 2023
				Prednisolone
EULAR2023	Not Applicable	Systemic Lupus Erythematosus Maintenance	117	Prednisolone withdrawal	mudkjqaics(wuzfiruotm) = cryfmvrrhu zbgkamhjuc (wgswbncntu ) View more	-	31 May 2023
				Immunosuppressant withdrawal	mudkjqaics(wuzfiruotm) = vryntwbmra zbgkamhjuc (wgswbncntu ) View more
GLORIA (EULAR2023)	Not Applicable	Rheumatoid Arthritis Add-on	449	Prednisolone 5 mg/day	xxzecbuers(ncfrqqzcpp) = dncpnhqsnh wvhzqzxnrm (iahybenamd )	Positive	31 May 2023
				Placebo	xxzecbuers(ncfrqqzcpp) = jmhlegorsy wvhzqzxnrm (iahybenamd )
APAO2023	Not Applicable	Uveitic Glaucoma	-	Oral Prednisolone	grrhomimde(lxokipxnzv) = uutqnlxndf ieuhvvteqf (dggioufjmi, 10.2)	-	23 Feb 2023

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