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Bristol Myers Squibb announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of a new Opdivo (nivolumab) formulation associated with a new route of administration (subcutaneous use), a new pharmaceutical form (solution for injection) and a new strength (600 mg/vial).
Nivolumab for subcutaneous use co-formulated with recombinant human hyaluronidase (rHuPH20), is indicated across multiple previously approved adult solid tumours as monotherapy, monotherapy maintenance following completion of nivolumab plus Yervoy (ipilimumab) combination therapy, or in combination with chemotherapy or cabozantinib. The CHMP opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines in the European Union (EU).
“The positive CHMP opinion is an important step forward in the evolution of immuno-oncology and in the potential of subcutaneous nivolumab to help transform the lives of people living with cancer,” said Dana Walker, M.D., M.S.C.E., Opdivo global programme lead, Bristol Myers Squibb. “We look forward to bringing the same high-quality care that transformed cancer treatment with an administration method that has the potential to improve the patient experience and efficiency of healthcare systems in Europe."
The positive CHMP opinion is based on results from the CheckMate -67T trial, and additional data that demonstrated comparable pharmacokinetics and safety profiles between subcutaneous use of Opdivo and IV Opdivo , in which subcutaneous Opdivo demonstrated noninferiority of C avgd28 (time-averaged Opdivo serum concentration over 28 days) and C minss (trough serum concentration at steady state), the study’s primary endpoints, vs. intravenous (IV) Opdivo in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received no more than two prior lines of systemic therapy. The geometric mean ratio (GMR) for C avgd28 was 2.10 (90% CI: 2.00-2.20) and the GMR for C minss was 1.77 (90% CI: 1.63-1.93). Additionally, as a key powered secondary endpoint, the objective response rate (ORR) in the subcutaneous Opdivo arm (n=248) was 24% (95% CI: 19-30), compared with 18% (95% CI: 14-24) in the IV Opdivo arm (n=247), showing that subcutaneous Opdivo has similar efficacy compared to IV Opdivo. The safety profile of subcutaneous Opdivo was consistent with the IV formulation. The pharmacokinetics, efficacy and safety results from CheckMate -67T were presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. Additional safety analyses and patient reported outcomes were presented at the 2024 ASCO Annual Meeting and the European Society for Medical Oncology (ESMO) Congress.
In the EU, the EC delivers its final decision within approximately two months following receipt of the CHMP opinion. Once issued, the decision will be applicable to all EU member states as well as in the European Economic Area (EEA) countries Iceland, Norway and Liechtenstein.
On December 27, 2024, nivolumab and hyaluronidase-nvhy, marketed under the brand name Opdivo Qvantig, was approved by the US Food and Drug Administration (FDA).
Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -67T clinical trial.
CheckMate -67T is a phase 3, randomized, open-label, noninferiority trial evaluating subcutaneous administration of Opdivo co-formulated with Halozyme’s proprietary recombinant human hyaluronidase rHuPH20, or subcutaneous nivolumab compared to intravenous (IV) Opdivo , in adult patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received prior systemic therapy. A total of 495 patients were randomized to receive either subcutaneous nivolumab (1,200 mg of nivolumab and 20,000 units of hyaluronidase) every 4 weeks subcutaneously (n = 248), or Opdivo 3 mg/kg every 2 weeks intravenously (n = 247). The coprimary endpoints are time-averaged concentration over 28 days (C avgd28 ) and minimum concentration at steady state (C minss ). The key powered secondary endpoint is overall response rate, as assessed by blinded independent central review.
Subcutaneous administration is delivery of treatment beneath the skin and is an alternative to IV infusion. There are several potential benefits of subcutaneous administration: it may offer the flexibility to provide and receive treatment where it is best for the healthcare provider and patient, may impact infusion chair capacity, and may reduce time spent preparing and administering treatment. It may also simplify administering treatment for patients who have difficult-to-access veins or do not want a port. Subcutaneous treatment has the potential to be administered by a healthcare professional without site of care restrictions.
Serious adverse reactions occurred in 28% of patients receiving subcutaneous nivolumab (n=247). The most frequent serious adverse reactions reported in >1% of patients who received subcutaneous nivolumab were pleural effusion (1.6%), pneumonitis (1.6%), hyperglycemia (1.2%), hyperkalemia (1.2%), hemorrhage (1.2%) and diarrhea (1.2%). The most common adverse reactions (=10%) in patients treated with subcutaneous nivolumab (n=247) were musculoskeletal pain (31%), fatigue (20%), pruritus (16%), rash (15%), hypothyroidism (12%), diarrhoea (11%), cough (11%), and abdominal pain (10%). Fatal adverse reactions occurred in 3 (1.2%) patients who received subcutaneous nivolumab; these included myocarditis, myositis, and colitis complications. Study therapy was discontinued in 10% of patients due to adverse reactions. The safety profile of subcutaneous nivolumab was comparable with the safety profile of IV 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-tumour immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including phase 3, in a variety of tumour types. To date, the Opdivo clinical development programme has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with Yervoy; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with Yerrvoy and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238– adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K– adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with Yervoy; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with Yervoy; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 648–previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 040–hepatocellular carcinoma, in combination with Yervoy; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with Yervoy; Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with Yervoy; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with Yervoy; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
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