|Name/Company||Approval Dates and Comments|
Dabrafenib mesilate capsule
In May 2013, the US FDA approved this BRAF kinase inhibitor as a single-agent oral treatment for unresectable melanoma or metastatic melanoma in adult patients whose tumors express the BRAF V600E gene mutation. Dabrafenib is not indicated for treating patients with wild-type BRAF melanoma. The mutation must be detected by an FDA-approved test, such as the companion diagnostic assay from bioMérieux S.A., THxID™- BRAF. Dabrafenib inhibits certain mutated BRAF kinases that activate the BRAF pathway and drive tumor cell growth. In clinical investigations the most common adverse reactions included hyperkeratosis (37%), headache (32%), pyrexia (28%), arthralgia (27%), papilloma (warts) (27%), alopecia (hair loss) (22%), palmar-plantar erythrodysesthesia (redness, swelling, peeling or tenderness of hands or feet) (20%), rash (17%), back pain (12%), cough (12%), myalgia (11%), constipation (11%) and nasopharyngitis (10%).
Trametinib dimethyl sulfoxide tablet
In May 2013, the FDA approved this MEK1/MEK2 inhibitor as a single-agent oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations. These mutations must be detected by an FDAapproved test, such as the companion diagnostic assay THxID™- BRAF (bioMérieux S.A.). Treatment is not indicated for patients who have received prior BRAF inhibitor therapy. Trametinib specifically binds to and inhibits MEK1 and MEK2, resulting in an inhibition of growth factor-mediated cell signalling and cellular proliferation in various cancers. In clinical investigations the most common adverse reactions included rash (57%), diarrhoea (43%), lymphoedema (32%), dermatitis acneiform (19%), stomatitis (15%), hypertension (15%), abdominal pain (13%), haemorrhage (13%), dry skin (11%), pruritis (10%) and paronychia (10%).
Australia’s Therapeutic Goods Administration (TGA) approved this hedgehog pathway inhibitor n May 2013 for the treatment of adult patients with metastatic basal cell carcinoma (BCC). The drug is administered orally once-daily and is indicated for patients with locally advanced BCC who are not candidates for surgery or radiation and for patients with metastatic BCC.
In April 2013, Merck & Co. announced that the FDA assigned a Breakthrough Therapy designation to the experimental drug lambrolizumab (MK-3475) for the treatment of patients with advanced melanoma. Lambrolizumab is an investigational antibody designed to target the Programmed Death-1 (PD-1) pathway in patients with advanced melanoma. Interim results from a Phase 1B trial unveiled data on 85 of 132 patients enrolled in the singlearm study, reporting that 43 patients (51%) showed an objective antitumor response and 8 patients (9%) achieved a complete response at or after an imaging assessment performed at 12 weeks. Furthermore, 11 of 27 patients (41%) who had been previously treated with ipilimumab monotherapy for late-stage melanoma showed an objective antitumor response. Treatment was generally well-tolerated, with the most common adverse events including fatigue, rash, diarrhea, nausea, cough, joint pain, fever, and pruritus.
Breakthrough Therapy designation is assigned by the FDA to drugs that treat life-threatening conditions and demonstrate a substantial improvement over currently approved therapies. The designation offers the opportunity for an expedited review process, allowing for increased interaction between the FDA and the developer, requiring fewer patients for clinical trials, and reducing the time required to conduct such studies.
More information is available at: http://www.mercknewsroom.com/press-release/researchand-development-news/merck-announces-breakthrough-therapy-designation-lambrol