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Regulatory Update - GSK receives positive CHMP opinions for Tafinlar® (dabrafenib) and Tyverb® (lapatinib)

GSK announces that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) is recommending marketing authorisation for two cancer drugs.

Issued: London UK

Today, GlaxoSmithKline plc (GSK) announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) is recommending marketing authorisation for two cancer drugs. CHMP issued positive opinions for:

· Tafinlar® (dabrafenib) as treatment for adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

· Tyverb® (lapatinib) in combination with trastuzumab as a treatment for adult patients with breast cancer, whose tumours overexpress HER2 (ErbB2) with hormone receptor-negative metastatic disease that has progressed on prior trastuzumab therapy(ies) in combination with chemotherapy. 

“We are delighted by the positive opinions issued by CHMP on lapatinib and dabrafenib. They represent evidence of our commitment to patients living with cancer and they could bring new treatment options for European patients living with specific types of advanced breast cancer and melanoma.” said Dr. Rafael Amado, Head of Oncology R&D, GlaxoSmithKline.

A CHMP positive opinion is one of the final steps before marketing authorisation is granted by the European Commission, but does not always result in marketing authorisation.

About Tafinlar® (dabrafenib)

Dabrafenib is not approved or licensed in the EU as treatment for adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

The safety profile is based on data from five clinical monotherapy studies and included 578 patients with melanoma. The most frequently occurring adverse drug reactions (ADRs) (³ 15 %) reported with dabrafenib were hyperkeratosis, headache, pyrexia, arthralgia, fatigue, nausea, papilloma, alopecia, rash and vomiting.

Important Safety Information for Tafinlar®

Pyrexia: Fever has been reported in clinical trials. Serious non-infectious febrile events, identified as fever accompanied by severe rigors, dehydration, hypotension and/or acute renal insufficiency in the absence of infection, have occurred. Evaluate for infection. Interrupt and/or reduce dosing as recommended, consider prophylaxis when restarting therapy.

Cutaneous Squamous Cell Carcinoma (cuSCC) and New Primary Melanoma:CuSCC including keratoacanthomas and new primary melanomas have occurred. Patients should have periodic skin examinations for new cutaneous malignancy. CuSCC and new melanomas should be managed by dermatological excision and patients should continue treatment without dose adjustment.

Non-Cutaneous Secondary/Recurrent Malignancy: Paradoxical activation of signalling in BRAF wild-type cells which have RAS mutations may occur when exposed to dabrafenib, which may result in increased risk of non-cutaneous malignancies. Patients should be evaluated for non-cutaneous malignancies prior to therapy and should be monitored during and after treatment as clinically appropriate.

Renal Failure: Renal failure has occurred, generally associated with pyrexia and dehydration. Monitor serum creatinine during therapy and interrupt or reduce dosing as recommended. Caution should be used in patients with renal insufficiency.

Uveitis: Uveitis and iritis have occurred. Monitor patients for visual signs and symptoms during therapy.

Pancreatitis: Pancreatitis has been reported. Evaluate serum amylase and lipase for unexplained abdominal pain and monitor closely when re-starting therapy.

QT Prolongation: QT prolongation has been reported. Treatment is not recommended for patients with uncorrectable electrolyte abnormalities, long QT syndrome or patients taking medications that may prolong the QT interval. Monitor ECG and electrolytes and interrupt, reduce, or discontinue dosing as recommended.

About Tyverb® (lapatinib)
Lapatinib is not approved or licensed in the EU in combination with trastuzumab for adult patients with breast cancer, whose tumours overexpress HER2 (ErbB2) with hormone receptor-negative metastatic disease that has progressed on prior trastuzumab therapy(ies) in combination with chemotherapy. For the EU SPC for TYVERB (lapatinib) please visit: http://health.gsk.com/

In the Phase III trial of lapatinib and trastuzumab compared to lapatinib alone in patients with HER2-positive metastatic breast cancer whose disease has progressed on trastuzumab-containing regimens, the most frequent adverse reactions (> 20%) during therapy with lapatinib and trastuzumab were diarrhoea (62%), nausea (28%), rash (23%), and fatigue (22 %).

Important Safety Information for Tyverb®

Cardiac toxicity: Lapatinib has been associated with reports of decreases in LVEF. Lapatinib has not been evaluated in patients with symptomatic cardiac failure. Caution should be taken if Tyverb is to be administered to patients with conditions that could impair left ventricular function (including coadministration with potentially cardiotoxic medicinal products. Evaluation of cardiac function, including LVEF determination, should be conducted for all patients prior to initiation of treatment with Tyverb to ensure that the patient has a baseline LVEF that is within the institutions normal limits. LVEF should continue to be evaluated during treatment with Tyverb to ensure that LVEF does not decline to an unacceptable level. In studies across the clinical development programme for lapatinib, cardiac events including LVEF decreases were reported in approximately 1% of patients. Symptomatic LVEF decreases were observed in approximately 0.3% of patients who received lapatinib, however when lapatinib was administered in combination with trastuzumab in the metastatic setting, the incidence of cardiac events including LVEF decreases was higher (7%) versus the lapatinib alone arm (2%) in the pivotal trial. The cardiac events observed in this study were comparable in nature and severity to those previously seen with lapatinib. Caution should be taken if Tyverb is administered to patients with conditions that could result in prolongation of QTc (including hypokalemia, hypomagnesemia, congenital long QT syndrome, or co-administration of other medicinal product known to cause QT prolongation). Hypokalemia or hypomagnesemia should be corrected prior to treatment. Electrocardiograms with QT measurement should be considered prior to administration of Tyverb and throughout treatment.

Diarrhoea: Diarrhoea, including severe diarrhoea, has been reported with Tyverb treatment. Diarrhoea can be potentially life-threatening if accompanied by dehydration, renal insufficiency, neutropenia and/or electrolyte imbalances and fatal cases have been reported. Diarrhoea generally occurs early during Tyverb treatment, with almost half of those patients with diarrhoea first experiencing it within 6 days. Lapatinib-induced diarrhoea is usually low-grade, with severe diarrhoea of NCI CTCAE grades 3 and 4 occurring in < 10% and <1% of patients, respectively.  Proactive management of diarrhoea with anti-diarrhoeal medicinal product is important. Severe cases of diarrhoea may require administration of oral or intravenous electrolytes and fluids, use of antibiotics such as fluoroquinolones (especially if diarrhoea is persistent beyond 24 hours, there is fever, or grade 3 or 4 neutropenia) and interruption or discontinuation of Tyverb therapy.

Interstitial lung disease and pneumonitis: Lapatinib has been associated with reports of pulmonary toxicity including interstitial lung disease and pneumonitis. Patients should be monitored for symptoms of pulmonary toxicity (dyspnoea, cough, fever) and treatment discontinued in patients who experience symptoms which are NCI CTCAE grade 3 or greater. Pulmonary toxicity may be severe and lead to respiratory failure. Fatal cases have been reported, causality of the deaths is uncertain.

Hepatotoxicity: Hepatotoxicity has occurred with Tyverb use and may in rare cases be fatal. The hepatotoxicity may occur days to several months after initiation of treatment. At the initiation of treatment, patients should be advised of the potential for hepatotoxicity. Liver function (transaminases, bilirubin and alkaline phosphatase) should be monitored before the initiation of treatment and monthly thereafter, or as clinically indicated. Tyverb dosing should be discontinued if changes in liver function are severe and patients should not be retreated. Caution is warranted if Tyverb is prescribed to patients with moderate or severe hepatic impairment. Caution is advised if Tyverb is prescribed to patients with severe renal impairment.

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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect GSK' s operations are described under Item 3.D 'Risk factors' in the company's Annual Report on Form 20-F for 2012.