| Monoclonal antibody | |
|---|---|
| Type | ? |
| Target | GDF-15 |
| Clinical data | |
| Other names | PF-06946860 |
| Legal status | |
| Legal status |
|
| Identifiers | |
| CAS Number | |
| UNII | |
Ponsegromab (PF-06946860) is a monoclonal antibody that works as a GDF-15 inhibitor. It is developed by Pfizer for cancer cachexia. [1] [2] [3] [4] [5]
In September 2024, Pfizer disclosed that ponsegromab led to significant body weight increases in patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer in a phase 2 clinical trial. [6]
Cachexia is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and AIDS. Systemic inflammation from these conditions can cause detrimental changes to metabolism and body composition. In contrast to weight loss from inadequate caloric intake, cachexia causes mostly muscle loss instead of fat loss. Diagnosis of cachexia can be difficult due to the lack of well-established diagnostic criteria. Cachexia can improve with treatment of the underlying illness but other treatment approaches have limited benefit. Cachexia is associated with increased mortality and poor quality of life.
Torcetrapib was a drug being developed to treat hypercholesterolemia and prevent cardiovascular disease. Its development was halted in 2006 when phase III studies showed excessive all-cause mortality in the treatment group receiving a combination of atorvastatin (Lipitor) and torcetrapib.
Sunitinib, sold under the brand name Sutent, is an anti-cancer medication. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) in January 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.
Megestrol acetate (MGA), sold under the brand name Megace among others, is a progestin medication which is used mainly as an appetite stimulant to treat wasting syndromes such as cachexia. It is also used to treat breast cancer and endometrial cancer, and has been used in birth control. Megestrol acetate is generally formulated alone, although it has been combined with estrogens in birth control formulations. It is usually taken by mouth.
Cediranib is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases.
Growth/differentiation factor 15 is a protein that in humans is encoded by the GDF15 gene. GDF15 was first identified as Macrophage inhibitory cytokine-1 or MIC-1.
Axitinib, sold under the brand name Inlyta, is a small molecule tyrosine kinase inhibitor developed by Pfizer. It has been shown to significantly inhibit growth of breast cancer in animal (xenograft) models and has shown partial responses in clinical trials with renal cell carcinoma (RCC) and several other tumour types.
Crizotinib, sold under the brand name Xalkori among others, is an anti-cancer medication used for the treatment of non-small cell lung carcinoma (NSCLC). Crizotinib inhibits the c-Met/Hepatocyte growth factor receptor (HGFR) tyrosine kinase, which is involved in the oncogenesis of a number of other histological forms of malignant neoplasms. It also acts as an ALK and ROS1 inhibitor.
ALK inhibitors are anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase (ALK) such as an EML4-ALK translocation. They fall under the category of tyrosine kinase inhibitors, which work by inhibiting proteins involved in the abnormal growth of tumour cells. All the current approved ALK inhibitors function by binding to the ATP pocket of the abnormal ALK protein, blocking its access to energy and deactivating it. A majority of ALK-rearranged NSCLC harbour the EML4-ALK fusion, although as of 2020, over 92 fusion partners have been discovered in ALK+ NSCLC. For each fusion partner, there can be several fusion variants depending on the position the two genes were fused at, and this may have implications on the response of the tumour and prognosis of the patient.
Angiokinase inhibitors are a new therapeutic target for the management of cancer. They inhibit tumour angiogenesis, one of the key processes leading to invasion and metastasis of solid tumours, by targeting receptor tyrosine kinases. Examples include nintedanib, afatinib and motesanib.
Palbociclib, sold under the brand name Ibrance among others, is a medication developed by Pfizer for the treatment of HR-positive and HER2-negative breast cancer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be approved as a cancer therapy.
Resminostat is an orally bioavailable inhibitor of histone deacetylases (HDACs), of which inhibitors are antineoplastic agents.
Anamorelin (INN), also known as anamorelin hydrochloride, is a non-peptide, orally-active, centrally-penetrant, selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) with appetite-enhancing and anabolic effects which is under development by Helsinn Healthcare SA for the treatment of cancer cachexia and anorexia.
Darolutamide, sold under the brand name Nubeqa, is an antiandrogen medication which is used in the treatment of non-metastatic castration-resistant prostate cancer in men. It is specifically approved to treat non-metastatic castration-resistant prostate cancer (nmCRPC) in conjunction with surgical or medical castration. The medication is taken by mouth twice per day with food.
Gosogliptin is a drug for the treatment of type II diabetes. It is in the class of dipeptidyl peptidase-4 (DPP-4) inhibitors. It was discovered and developed through Phase 1 and Phase 2 by Pfizer. The crystal structure of DPP-4 in complex with gosogliptin is available. Its metabolism, excretion and pharmacokinetics in rat, dog and human have been described. A cost efficient route has been published. Other studies including Phase 3 studies were conducted in Russia. It is approved for use in Russia.
RET kinase inhibitors are a type of targeted cancer treatment that block abnormally activated RET proto-oncogene, a protein involved in cell growth. These inhibitors are used to treat cancers like non-small cell lung cancer, medullary thyroid carcinoma, and some types of colorectal and pancreatic cancer.
G1 Therapeutics, Inc. is an American biopharmaceutical company headquartered in Research Triangle Park, North Carolina. The company specializes in developing and commercializing small molecule therapeutics for the treatment of patients with cancer.
Defactinib is an inhibitor of PTK2, also known as focal adhesion kinase (FAK), Pyk2, and MELK which was developed by Pfizer and licensed to Verastem Oncology as a potential treatment for solid tumors.
Zabadinostat is an experimental epigenetic drug being investigated as a potential treatment for advanced or metastatic cancers. It is an orally available Class I selective histone deacetylase (HDAC) inhibitor, with half maximal inhibitory concentrations (IC50) of 62 nM, 570 nM and 550 nM, against HDAC1, HDAC2 and HDAC3, respectively. It shows no activity against HDAC class II.
Foscenvivint is a CREB-binding protein/β-catenin inhibitor that is developed for the treatment of liver diseases such as primary biliary cholangitis, hepatocellular carcinoma, and hepatitis C and B virus-induced liver cirrhosis.
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