Ipilimumab (Yervoy®) is an anti-cytotoxic T-lymphocyte antigen (CTLA)-4 monoclonal antibody that has been approved in the US for the first- or second-line treatment of patients with malignant melanoma. In the EU, it is awaiting approval as second-line therapy for melanoma. Ipilimumab blocks the effects of the negative T-cell regulator CTLA-4, which may in turn augment T-cell responses to tumour cells. Preclinical studies have indicated that antibody blocking of CTLA-4 can lead to potent immune responses. Ipilimumab is also in development as first- and second-line therapy for prostate cancer where it has progressed to phase III clinical trials worldwide, and it is in phase II development for non-small cell lung cancer. Ipilimumab was originated by the University of California, Berkeley, in the US and subsequently licensed to Medarex, which was later acquired by Bristol-Myers Squibb. This article summarizes the milestones in the development of intravenous ipilimumab leading to this first approval. This profile has been extracted from Wolters Kluwer's R&D Insight drug pipeline database. R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

Vivus' proprietary oral capsule containing phentermine and extended-release (ER) topiramate has been approved in the US for the treatment of obesity. Phentermine is an appetite suppressant, while topiramate is an anti-epileptic medication. The once-daily formulation, known as Qsymia™, is designed to produce weight loss by decreasing appetite and increasing satiety. The product is also in clinical development for sleep apnoea syndrome and type 2 diabetes mellitus. This article summarizes the milestones in the development of phentermine/topiramate ER leading to this first approval for obesity.

Mogamulizumab (Poteligeo®) is a defucosylated, humanized monoclonal antibody targeting CC chemokine receptor 4 (CCR4). Development is being carried out by its owner Kyowa Hakko Kirin for various haematological malignancies, and by licensee Amgen for asthma. Mogamulizumab was conceived through Kyowa Hakko Kirin's Potelligent® technology, which produces antibodies with enhanced antibody-dependent cellular cytotoxicity. This is achieved largely by reducing fucose content in the oligosaccharide structure of the Fc region. Mogamulizumab has been approved in Japan for the treatment of relapsed or refractory adult T-cell leukaemia-lymphoma (ATL) and is the first Potelligent® antibody to receive marketing approval anywhere in the world. Phase II development is underway for adult T-cell leukaemia-lymphoma (ATL) and cutaneous T-cell lymphoma in the US, and for peripheral T-cell lymphoma in the US and Europe. Amgen is conducting a phase I US-based study in patients with asthma. This article summarizes the milestones in the development of intravenous mogamulizumab leading to this first approval.

Vandetanib is an orally active antagonist of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), epidermal growth factor receptor (EGFR or HER1 or ErbB1) and RET kinase, and is now available in the US for the treatment of metastatic medullary thyroid cancer (MTC). Regulatory submissions for this indication have been filed in the EU and Canada, with clinical development in malignant MTC ongoing in several other countries. Vandetanib is being developed by AstraZeneca, and is also in phase II development for biliary, breast and prostate cancer. Earlier, AstraZeneca withdrew regulatory filings for non-small cell lung cancer (NSCLC) in the US and EU, and later discontinued development. This article summarizes the milestones in the development of vandetanib leading to this first approval in malignant MTC.

Linaclotide is a once-daily, orally administered, first-in-class agonist of guanylate cyclase-C that is minimally absorbed. It is being developed to treat gastrointestinal disorders by Ironwood Pharmaceuticals and its partners, Forest Laboratories (North America), Almirall (Europe) and Astellas Pharma (Asia-Pacific). Linaclotide has received its first global approval in the US for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC), and a marketing submission has been filed in the EU for IBS-C. This article summarizes the milestones in the development of linaclotide leading to this first approval for IBS-C and CIC. This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.