Date: 2013-09-02
Type of information: Granting of a Market Authorisation in the EU
Product name: Tafinlar®
Compound: dabrafenib
Therapeutic area: Cancer - Oncology
Action mechanism:
Company: Novartis (Switzerland)
Disease:
Latest news:
• On May 29, 2013, the FDA has approved Tafinlar® (dabrafenib) for patients with advanced (metastatic) or unresectable (cannot be removed by surgery) melanoma. Tafinlar®, a BRAF inhibitor, is approved to treat patients with melanoma whose tumors express the BRAF V600E gene mutation. Tafinlar®is not indicated for the treatment of patients with wild-type BRAF melanoma.
The approval of dabrafenib is based on results from one multicenter, international trial, specifically the pivotal, open-label Phase III BREAK-3 study that randomised 250 previously untreated adult patients with BRAF V600E mutation-positive unresectable or metastatic melanoma to receive dabrafenib or dacarbazine (chemotherapy) in a 3:1 ratio, respectively. The primary endpoint was progression-free survival (PFS) as assessed by the investigator. Other pre-specified endpoints included independent radiology review committee (IRRC) assessed PFS, confirmed objective response rate (ORR) and duration of response. Twenty-eight patients (44%) crossed over from the dacarbazine arm at the time of disease progression to receive dabrafenib.The study demonstrated a statistically significant increase in PFS in patients treated with dabrafenib, compared to dacarbazine (HR=0.33; [95% CI: 0.20, 0.54], p<0.0001). The median PFS was 5.1 months with dabrafenib (95% CI: 4.9, 6.9) compared to 2.7 months with dacarbazine (95% CI: 1.5, 3.2). The ORR with dabrafenib was 52 percent (95% CI: 44, 59) versus 17 percent with dacarbazine (95% CI: 9, 29).
The FDA approved Tafinlar® with a genetic test called the THxID BRAF test, a companion diagnostic that will help determine if a patient’s melanoma cells have the V600E or V600K mutation in the BRAF gene. In 2010, GSK entered a collaboration with bioMérieux to develop a companion diagnostic test to detect BRAF V600 (V600E and V600K) gene mutations found in several cancers, including melanoma. bioMérieux has received FDA pre-market approval of THxID™-BRAF. Currently, it is the only FDA-approved test that detects the V600K mutation.
GSK will be making Tafinlar® available for prescription no later than in the early third quarter of 2013.
The recommended dose and schedule for dabrafenib is 150 mg orally twice daily until disease progression or unacceptable toxicity. Dabrafenib should be taken at least one hour before or two hours after a meal. Confirmation of the presence of BRAF V600E is needed prior to initiation of dabrafenib because of the risks of potential risk of tumor promotion in patients with BRAF wild-type melanoma.
The most serious side effects reported in patients receiving Tafinlar® included an increased risk of skin cancer (cutaneous squamous cell carcinoma), fevers that may be complicated by hypotension (low blood pressure), severe rigors (shaking chills), dehydration, kidney failure and increased blood sugar levels requiring changes in diabetes medication or the need to start medicines to control diabetes. The most common side effects reported in patients receiving Tafinlar®included thickening of the skin (hyperkeratosis), headache, fever, joint pain, non-cancerous skin tumors, hair loss and hand-foot syndrome.
• On August 3, 2012, GSK has announced regulatory submissions in the European Union and United States (US) related to single-agent use of its BRAF inhibitor dabrafenib to treat patients with BRAF V600 mutation positive metastatic melanoma, specifically:
· A Marketing Authorisation Application to the European Medicines Agency for dabrafenib for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.
· A New Drug Application to the US Food and Drug Administration for dabrafenib for the treatment of patients with unresectable or metastatic melanoma with BRAF V600 mutation as detected by an FDA-approved test.
GSK entered a collaboration with bioMérieux in 2010 to develop a molecular theranostic test to detect BRAF V600 (V600E and V600K) gene mutations found in several cancers, including melanoma. bioMérieux has filed for FDA Pre-Market Approval of the test and it is currently being utilised in the Phase III trametinib-dabrafenib combination programme to identify appropriate patients.
Patents:
Submission of marketing authorization application USA : 2012-08-03
Submission of marketing authorization application UE: 2012-08-03
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2013-05-29
UE authorization: 2013-08-30
Favourable opinion UE: 2013-06-27
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
