On July 19, 2024 Bristol Myers Squibb (NYSE: BMY) reported that the European Medicines Agency (EMA) validated its Type II variation application for Opdivo (nivolumab) plus Yervoy (ipilimumab) as a potential first-line treatment option for adult patients with unresectable or advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy (Press release, Bristol-Myers Squibb, JUL 19, 2024, View Source [SID1234644972]). The application was based on results from the Phase 3 CheckMate -9DW trial and validation of the application confirms the submission is complete and begins the EMA’s centralized procedure review.

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"Approximately 62,000 cases of liver cancer are diagnosed annually in the European Union, with HCC being the predominant type. Despite recent treatment advances, the prognosis remains poor for patients in more advanced stages which highlights the need for therapies with better clinical outcomes," said Dana Walker, M.D., M.S.C.E., vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb. "We look forward to working with the EMA to advance our application for Opdivo plus Yervoy to provide a new first-line dual immunotherapy combination treatment option for adult patients with unresectable or advanced hepatocellular carcinoma in the European Union."

In the Phase 3 CheckMate -9DW trial, Opdivo plus Yervoy demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) compared to investigator’s choice of lenvatinib or sorafenib, which showed the clinical benefit of the combination treatment option when provided in the first-line setting. The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified. Results were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Bristol Myers Squibb thanks the patients and investigators involved with the Phase 3 CheckMate -9DW clinical trial.

About CheckMate -9DW

CheckMate -9DW is a Phase 3 randomized, open-label trial evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib monotherapy in patients with unresectable or advanced hepatocellular carcinoma who have not received prior systemic therapy.

Approximately 668 patients were randomized to receive Opdivo plus Yervoy (Opdivo 1mg/kg plus Yervoy 3 mg/kg Q3W for up to four doses, followed by Opdivo monotherapy 480 mg for a maximum duration of 2 years) infusion, or single agent lenvatinib or sorafenib as oral capsules in the control arm. The primary endpoint of the trial is overall survival and key secondary endpoints include objective response rate and time to symptom deterioration.

About Hepatocellular Carcinoma

Liver cancer is the third most frequent cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and accounts for 75% – 85% of all liver cancers. HCC is often diagnosed in an advanced stage, where effective treatment options are limited and are usually associated with poor outcomes.

Up to 70% of patients experience recurrence within five years, particularly those still considered to be at high risk after surgery or ablation. While most cases of HCC are caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, metabolic syndrome and nonalcoholic steatohepatitis (NASH) are rising in prevalence and expected to contribute to increased rates of HCC.

On July 18, 2024 – Ono Pharmaceutical, Co., Ltd. (Headquarters: Osaka, Japan; President: Toichi Takino; "Ono") reported that the European Medicines Agency (EMA) has accepted the marketing authorization application (MAA) for vimseltinib, a colony stimulating factor 1 receptor (CSF1R), for the treatment of patients with tenosynovial giant cell tumor (TGCT), which is under development by Deciphera Pharmaceuticals, Inc. ("Deciphera"), a wholly-owned subsidiary of Ono (Press release, Deciphera Pharmaceuticals, JUL 19, 2024, View Source [SID1234644952]). The review of the MAA begins under the EMA’s centralized review process for all 27 member states of the European Union (EU), as well as Iceland, Liechtenstein and Norway. Vimseltinib was granted Orphan Drug Designation for the treatment of TGCT by the EMA in December 2019.

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"Building upon positive results from the MOTION pivotal Phase 3 study, we are excited to initiate the regulatory review process in the EU and we are one step closer in our mission to bring vimseltinib to TGCT patients in need of an effective and well-tolerated treatment" said Steve Hoerter, President and Chief Executive Officer of Deciphera Pharmaceuticals.

The submission is supported by the data from the pivotal Phase 3 MOTION study, evaluating the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery with no prior antiCSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed), compared to placebo. In the study, vimseltinib demonstrated a statistically significant and clinically meaningful objective response rate (ORR) at Week 25 in the intent-to-treat (ITT) population, as assessed by Blinded Independent Radiologic Review (BIRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), versus placebo (40% in vimseltinib arm vs 0% in placebo arm, p <0.0001). Additionally, vimseltinib demonstrated statistically significant and clinically meaningful improvements versus placebo in all key secondary endpoints. The safety profile of vimseltinib is manageable and safety data from MOTION are consistent with data previously disclosed in the Phase 1/2 clinical trial of vimseltinib*. Data from the MOTION study was presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

*: Gelberblom, et at. 2024 ASCO (Free ASCO Whitepaper) Annual Meeting

About the MOTION Study

The MOTION study is a two-part, randomized, double-blind, placebo-controlled Phase 3 clinical study to assess the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed). The primary endpoint of the study is an objective response rate (ORR) at Week 25 in the intent-to-treat (ITT) population, as assessed by Blinded Independent Radiologic Review (BIRR) per using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), versus placebo. The secondaryendpoint includes ORR per tumor volume score (TVS), active range of motion (ROM), physical function, stiffness, quality of life, and pain, all assessed at Week 25. This study consists of two Parts. In Part 1, patients were randomized to receive either vimseltinib or placebo for 24 weeks. In Part 2, patients randomized to placebo in Part 1 have the option to receive vimseltinib, and all patients receive vimseltinib for a long-term period in an open-label setting.

About Tenosynovial Giant Cell Tumor (TGCT)

TGCT is a rare disease caused by a translocation in colony-stimulating factor 1 (CSF1) gene resulting in overexpression of CSF1 and recruitment of colony-stimulating factor 1 receptor (CSF1R)-positive inflammatory cells into the lesion. TGCT is a rare, non-malignant tumor that develops inside or near joints. TGCT is caused by dysregulation of the CSF1 gene leading to overproduction of CSF1. TGCT is also known as giant cell tumor of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS), a diffuse-type of TGCT. Although benign, these tumors can grow and cause damage to surrounding tissues and structures inducing pain, swelling, and limitation of movement of the joint. Surgery is the main treatment option; however, these tumors tend to recur, particularly in diffuse-type TGCT. If untreated or if the tumor continually recurs, damage and degeneration may occur in the affected joint and surrounding tissues, which may cause significant disability. For a subset of patients who are not amenable to surgery, systemic treatment options are limited and a new therapeutic option for TGCT is needed.

About Vimseltinib

Vimseltinib is an investigational, oral switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. Vimseltinib has been developed using Deciphera’s proprietary switch-control kinase inhibitor platform.

On July 18, 2024 Ono Pharmaceutical Co., Ltd. reported that Ono Pharma Korea Co., Ltd. ("OPKR"), a Korean subsidiary of Ono, received the additional approval of Opdivo (nivolumab) Intravenous Infusion ("Opdivo"), an anti-PD-1 antibody, in combination with cisplatin and gemcitabine on July 17 from the Ministry of Food and Drug Safety (MFDS) in South Korea, for the first-line treatment of patients with unresectable or metastatic urothelial carcinoma (Press release, Ono, JUL 18, 2024, View Source [SID1234646252]).

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This approval is based on results from the Phase 3 CheckMate -901 study (CA209-901: ONO-4538-56), evaluating Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy, compared to cisplatin-gemcitabine alone, in patients with previously untreated unresectable or metastatic urothelial carcinoma (UC). In this study, Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy demonstrated statistically significant and clinically meaningful improvements in the primary efficacy endpoints of overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR), compared to chemotherapy alone. The safety profile of the regimens in this study was consistent with the known safety profiles of the individual components of the regimen. No new safety concerns were identified

 With respect to the indication of UC, Opdivo monotherapy was approved in South Korea for the treatment of "locally advanced or metastatic urothelial carcinoma that has progressed on or following platinum-based chemotherapy" in August 2017, and "adjuvant treatment in patients with muscle-invasive bladder carcinoma (MIBC) at a high risk of recurrence after undergoing radical resection" in February 2022.

About CheckMate -901 Study (CA209-901: ONO-4538-56)
 CheckMate -901 is a randomized, open-label Phase 3 study, evaluating Opdivo in combination with Yervoy (ipilimumab) (primary study) or Opdivo in combination with cisplatin and gemcitabine followed by Opdivo monotherapy (sub-study) compared to standard-of-care cisplatin-gemcitabine alone, in patients with previously untreated unresectable or metastatic urothelial carcinoma.
 In the CheckMate -901 study, cisplatin-eligible patients were randomized to receive either Opdivo 360 mg in combination with cisplatin-gemcitabine every three weeks for up to six cycles followed by Opdivo 480 mg monotherapy every 4 weeks until disease progression or unacceptable toxicity up to a maximum of two years, or cisplatin-gemcitabine alone every three weeks for up to six cycles. The primary endpoints of this study were overall survival (OS) and progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR). The OS and PFS outcomes are based on the final efficacy analyses of these endpoints.
 The primary study is ongoing to assess Opdivo plus Yervoy versus standard-of-care chemotherapy.

About Urothelial Carcinoma
 Bladder cancer is the ninth most common cancer in the world, with more than 610,000 new cases diagnosed in 2022 and more than 220,000 people die from it each year. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but rates of recurrence and disease progression are high. Approximately 50% of patients who undergo radical surgery will experience disease recurrence, especially within the first two to three years after surgical removal of the bladder or kidney. For patients whose disease recurs as metastatic cancer, the prognosis is poor, with a median overall survival of approximately 12 to 14 months when treated with systemic therapy.

About Opdivo
 Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response by blocking the interaction between PD-1 and its ligands. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers since the approval for the treatment of melanoma in Japan in July 2014. Opdivo is currently approved in more than 65 countries, including Japan, South Korea, Taiwan, the US and European Union.
 In Japan, Ono launched Opdivo for the treatment of unresectable melanoma in September 2014. Thereafter, Opdivo received an approval for additional indications of unresectable, advanced or recurrent non-small cell lung cancer in December 2015, unresectable or metastatic renal cell carcinoma in August 2016, relapsed or refractory classical Hodgkin lymphoma in December 2016, recurrent or metastatic head and neck cancer in March 2017, unresectable advanced or recurrent gastric cancer which has progressed after chemotherapy in September 2017, unresectable advanced or recurrent malignant pleural mesothelioma which has progressed after chemotherapy in August 2018, microsatellite instability high (MSI-High) unresectable advanced or recurrent colorectal cancer that has progressed following chemotherapy and unresectable advanced or recurrent esophageal cancer that has progressed following chemotherapy in February 2020, cancer of unknown primary in December 2021, adjuvant treatment of urothelial carcinoma in March 2022, malignant mesothelioma (excluding malignant pleural mesothelioma) in November 2023, and unresectable advanced or recurrent malignant epithelial tumors in February 2024.
 In addition, Ono has been conducting clinical development program including hepatocellular carcinoma, ovarian cancer, etc.

About Ono and Bristol Myers Squibb Collaboration
 In 2011, through a collaboration agreement with Bristol Myers Squibb (BMS), Ono granted BMS its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to Opdivo except the US at the time. In July 2014, Ono and BMS further expanded their strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agent and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

On July 18, 2024 Boehringer Ingelheim, a leading research-driven biopharmaceutical company, reported significant progress in its pipeline across key therapeutic areas as it reached major milestones in the first half of the year (Press release, Boehringer Ingelheim, JUL 18, 2024, View Source [SID1234646116]).

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"We are stepping up our investments in R&D beyond our plans announced in April," said Hubertus von Baumbach, Chairman of the Board of Managing Directors. "The data read-outs that we received in MASH and will receive for oncology, mental health, and pulmonary fibrosis give us reason to accelerate our launch preparedness for these late-stage assets. We are pleased to see our pipeline developing at such pace."

Boehringer advanced its pipeline across clinical phases with five new phase I, II, or III initiations in cardiometabolic diseases, mental health, and oncology, and achieved two additional fast track designations for programs in inflammation. At the same time, the company announced nine R&D partnership agreements, significantly bolstering its human pharma portfolio across all therapeutic areas and tech platforms.

"As our pipelines continue to expand, both in depth and breadth, we need to apply a rigorous focus where we allocate our resources," said Frank Hübler, Member of the Board of Managing Directors with responsibility for Finance. "We want to accelerate our pipeline where we can, to deliver innovative medicines to patients ever faster."

Net sales rose by 7.4%* year-on-year to EUR 12.9 billion in the first six months of 2024, driven by ongoing high patient demand for Boehringer’s medications, especially for the JARDIANCE product family and OFEV in Human Pharma, and NEXGARD in Animal Health.

Human Pharma
As Boehringer prepares for its future portfolio and ongoing and upcoming launches, the past months were marked by developments across all focus therapy areas. For the remainder of the year, more news is expected across the portfolio with data read-outs in oncology (Zongertinib), mental health (Iclepertin) and pulmonary fibrosis (Nerandomilast).

The company’s efforts to advance holistic cardiovascular, renal and metabolic (CRM) health met some major milestones. Positive Phase II data for survodutide in metabolic dysfunction-associated steatohepatitis (MASH) showed groundbreaking results in liver disease due to MASH, with 83.0% of adults treated with survodutide achieving significant improvements versus 18.2% for placebo (response difference: 64.8%; CI 51.1%-78.6%, p<0.0001). Also, a sub analysis demonstrated that up to 64.5% of adults with fibrosis stages F2 and F3 (moderate to advanced scarring) achieved an improvement in fibrosis without worsening of MASH vs placebo, 25.9% [response difference: 38.6% (95% CI 18.1% – 59.1%), p=0.0005].1

The company initiated a Phase III trial in chronic heart failure for its novel selective aldosterone synthase inhibitor (ASi) in combination with empagliflozin. In an upcoming Phase III trial in chronic kidney disease for ASi, Boehringer will collaborate with Oxford Population Health.

Boehringer has joined a multi-year sponsorship of the American Heart Association’s Cardiovascular-Kidney-Metabolic Health Initiative. The initiative, which was announced recently, will allow the company to better understand the burden of people affected by diseases in these interconnected areas and enable better care.

Boehringer is committed to re-entering oncology with targeted investments. Phase Ia/Ib trial of Zongertinib, a HER2-specific tyrosine kinase inhibitor in patients with HER2 aberration-positive solid tumors, showed that Zongertinib was well tolerated and demonstrated promising efficacy. 2 The Brightline-1 trial investigating Brigimadlin in dedifferentiated liposarcoma did not meet its primary endpoint, though the benefit-risk assessment remains positive. Data for both oncology trials will be presented at conferences in the coming months.

In the first six months of 2024, the Human Pharma business grew by 9.3%* year on year. Net sales stood at EUR 10.3 billion. Growth was driven primarily by the JARDIANCE family and OFEV. To meet growing demand, the company continues high investments in its production and supply network. In January, Boehringer announced a further expansion and upgrade of its plant in Koropi, Greece. With an investment of EUR 120 million, the company will increase the manufacturing capacity of new and existing medications, some of them in the late-stage development.

Animal Health
In livestock, the VAXXITEK portfolio of poultry vaccines continues to expand and grew by 15.9%*. The company launched BULTAVO 3, a new vaccine that protects cattle and sheep against bluetongue virus serotype 3 (BTV-3). It is the first BTV-3 vaccine that prevents clinical signs and mortality. BULTAVO 3 has been licensed for emergency use in the Netherlands, Belgium, and Germany. Recent outbreaks of BTV-3 in the three countries caused severe losses for farmers and are threatening neighboring countries.

In the Animal Health business, growth was slower than expected in the first six months, with sales up 0.9%* compared to the same period last year to EUR 2.5 billion. This was primarily due to lower-than-expected sales in the U.S. pet business and challenging market conditions in China, especially impacting the swine vaccine business. Most other markets delivered solid growth.

With the recent launches of NEXGARD PLUS for dogs and NEXGARD COMBO for cats, sales of the NEXGARD parasiticides brands grew by 15.9%*. FRONTPRO, the first approved over-the-counter chewable tablet against ticks and fleas for dogs, is now available in most countries in Europe and continues to drive growth in the region. In pet therapeutics, sales of VETMEDIN, indicated for use in dogs with congestive heart failure, grew by 16.1%*.

Pipeline Outlook
Looking ahead, the company aims for up to 25 new treatment launches in Human Pharma until 2030. In Animal Health, 20 additional launches are expected across markets until 2026, including product updates, indication expansion and new products.

On July 18, 2024 Novartis reported the Second Quarter and Half Year 2024 (Presentation, Novartis, JUL 18, 2024, View Source [SID1234645117]).

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