Press Release: Novartis receives FDA approval of Tafinlar(R) + Mekinist(R) for adjuvant treatment of BRAF V600-mutant melanoma

Novartis International AG / Novartis receives FDA approval of

Tafinlar(R) + Mekinist(R) for adjuvant treatment of BRAF V600-mutant

melanoma. Processed and transmitted by Nasdaq Corporate Solutions. The

issuer is solely responsible for the content of this announcement.

-- Tafinlar + Mekinist is the first oral targeted adjuvant combination

therapy to demonstrate significant clinical benefit in patients with a

BRAF V600 mutation, following complete surgical resection

-- Tafinlar + Mekinist significantly reduced the risk of disease recurrence

or death compared to placebo by 53%[1]

-- New indication represents a new treatment option for patients in the US

with BRAF mutation-positive melanoma at risk of disease recurrence or

metastases, and is currently under regulatory review in Europe, Japan,

Canada and other countries worldwide

Basel, April 30, 2018 - Novartis announced today that the US Food and

Drug Administration (FDA) has approved Tafinlar(R) (dabrafenib) in

combination with Mekinist(R) (trametinib) for the adjuvant treatment of

patients with melanoma with BRAF V600E or V600K mutations, as detected

by an FDA-approved test, and involvement of lymph node(s), following

complete resection. The FDA granted the combination Breakthrough Therapy

Designation for this indication in October 2017 and Priority Review in

December 2017.

"Since the initial approval of Tafinlar and Mekinist in metastatic

melanoma in 2013, the combination has become an important therapy for

many patients carrying a BRAF mutation in both melanoma and lung cancers,

" said Liz Barrett, CEO, Novartis Oncology. "Today's FDA approval is an

important milestone for patients who previously had limited treatment

options in the adjuvant setting, and reflects our commitment to the

ongoing development of this breakthrough treatment."

The melanoma approval is based on results from COMBI-AD, a Phase III

study of 870 patients with Stage III BRAF V600E/K mutation-positive

melanoma treated with Tafinlar + Mekinist after complete surgical

resection[1]. Patients received the Tafinlar (150 mg BID) + Mekinist (2

mg QD) combination (n = 438) or matching placebos (n = 432)[1]. After a

median follow-up of 2.8 years, the primary endpoint of relapse-free

survival (RFS) was met. Treatment with the combination therapy

significantly reduced the risk of disease recurrence or death by 53% as

compared to placebo (HR: 0.47 [95% CI: 0.39-0.58]; p<0.0001; median not

reached with combination therapy vs. 16.6 months with placebo)[1]. The

RFS benefit among the combination arm was observed across all patient

subgroups, including disease sub-stage[1]. Improvements were also

observed in key secondary endpoints including overall survival (OS),

distant metastasis-free survival (DMFS) and freedom from relapse

(FFR)[1]. These results were published in the New England Journal of

Medicine, October 2017[1].

"The purpose of adjuvant therapy is to improve recurrence-free and

overall survival in our patients with melanoma. Adjuvant therapy options

are crucial today because more than half of patients have a recurrence

after surgery," said John M. Kirkwood, M.D., Usher Professor of Medicine,

Director of Melanoma and Skin Cancer, University of Pittsburgh. "We

developed the first adjuvant therapy approved by the FDA 22 years ago,

and now we have the first effective oral targeted therapy combination

that prevents relapse among patients with BRAF-mutated melanoma that has

spread to lymph nodes."

"Prevention and early detection are important safeguards from melanoma,

but that's only half the picture. Melanoma is an aggressive cancer that

can recur, particularly when it shows certain warning signs like

increased depth, ulceration, or spread to the lymph nodes," said Sancy

Leachman, M.D., Ph.D., Chair of the Department of Dermatology at OHSU

School of Medicine. "With proven treatment options for these patients,

it is important for dermatologists to assure that appropriate patients

are offered adjuvant treatment options - a 'watch and wait' approach is

no longer the standard of care. Collaborating with a multidisciplinary

care team of surgeons, pathologists and oncologists, and determining the

right treatment based on the patient's individual circumstances and

mutational status is crucial to our patients' care plans."

Adverse events (AEs) were consistent with other Tafinlar + Mekinist

studies, and no new safety signals were reported[1]. Of patients treated

with the combination, 97% experienced an AE, 41% had grade 3/4 AEs and

26% had AEs leading to treatment discontinuation (vs. 88%, 14%, and 3%,

respectively, with placebo)[1].

About COMBI-AD

The COMBI-AD study is a randomized, double-blind, placebo-controlled,

Phase III study and included a total of 870 patients with Stage III,

BRAF V600E/K-mutant melanoma who had undergone prior complete surgical

resection, without prior anticancer therapy. Patients were treated for

12 months and stratified based on BRAF mutation (V600E vs. V600K) and

stage (IIIA vs. IIIB vs. IIIC, based on American Joint Committee on

Cancer Melanoma of the Skin staging, 7(th) edition).

The primary endpoint was RFS. Secondary endpoints included OS, DMFS, FFR

and safety.

AEs were consistent with other Tafinlar + Mekinist studies, and no new

safety signals were reported[1].

About Melanoma

There are nearly 200,000 new diagnoses of melanoma (Stages 0-IV)

worldwide each year, approximately half of which have BRAF mutations.

Biomarker tests can determine whether a tumor has a BRAF mutation[2],

[3].

Some patients who receive surgical treatment for melanoma may have a

high risk of recurrence because melanoma cells can remain in the body

after surgery; almost half (44%) of patients receiving placebo per the

COMBI-AD study had a recurrence of disease within the first year[1],[4].

Adjuvant therapy is additional treatment given after surgical resection,

and may be recommended for patients with high-risk melanoma to help

reduce the risk of melanoma returning[4].

About Tafinlar and Mekinist

In the EU, Tafinlar in combination with Mekinist is approved for the

treatment of patients with a BRAF V600 mutation in metastatic melanoma

and non-small cell lung cancer (NSCLC).

In the US, Tafinlar in combination with Mekinist is approved for the

treatment of patients with unresectable or metastatic melanoma with BRAF

V600E or K mutations, as detected by an FDA-approved test, and for the

adjuvant treatment of melanoma with BRAF V600E or K mutations and

involvement of lymph node(s) following complete resection. Tafinlar +

Mekinist is also approved for BRAF V600E mutation-positive NSCLC.

Tafinlar and Mekinist are also indicated in more than 60 countries

worldwide, including the US and EU, as single agents to treat patients

with unresectable or metastatic melanoma with a BRAF V600 mutation.

Indications vary by country and not all indications are available in

every country. The safety and efficacy profile of Tafinlar and Mekinist

have not yet been established outside the approved indications. Because

of the uncertainty of clinical trials, there is no guarantee that

Tafinlar and Mekinist will become commercially available for additional

indications anywhere else in the world.

Tafinlar + Mekinist Combination Important Safety Information

Tafinlar + Mekinist combination may cause serious side effects.

Tafinlar in combination with Mekinist should only be used to treat

patients with a change (mutation) in the BRAF gene; therefore, doctors

should test their patients before treatment, as patients without a BRAF

mutation and with a RAS mutation can be at risk of increased cell

proliferation in the presence of a BRAF inhibitor.

Doctors should also consider other treatment options for their patients

if they had been previously treated with a BRAF inhibitor as single

agent, as the limited data available have shown that the efficacy of

Tafinlar + Mekinist is lower in these patients.

When Tafinlar is used in combination with Mekinist, or when Tafinlar is

administered as monotherapy, it can cause new cancers (both skin cancer

and non-skin cancer). Patients should be advised to contact their doctor

immediately for any new lesions, changes to existing lesions on their

skin, or signs and symptoms of other malignancies.

Tafinlar in combination with Mekinist, or Mekinist alone, can cause

severe bleeding, and in some cases can lead to death. Patients should be

advised to call their healthcare provider and get medical help right

away if they have headaches, dizziness, or feel weak, cough up blood or

blood clots, vomit blood or their vomit looks like "coffee grounds,"

have red or black stools that look like tar, or any unusual signs of

bleeding.

Tafinlar in combination with Mekinist, or either drug alone, can cause

severe eye problems that can lead to blindness. Patients should be

advised to call their healthcare provider right away if they get these

symptoms of eye problems: blurred vision, loss of vision, or other

vision changes, seeing color dots, halo (seeing blurred outline around

objects), eye pain, swelling, or redness.

Tafinlar in combination with Mekinist, or Tafinlar alone, can cause

fever which may be serious. When taking Tafinlar in combination with

Mekinist, fever may happen more often or may be more severe. In some

cases, chills or shaking chills, too much fluid loss (dehydration), low

blood pressure, dizziness, or kidney problems may happen with the fever.

Patients should be advised to call their healthcare provider right away

if they get a fever above 38.5(o) C (101.3(o) F) while taking Tafinlar.

Tafinlar in combination with Mekinist, or Mekinist alone, can affect how

well the heart pumps blood. A patient's heart function should be checked

before and during treatment. Patients should be advised to call their

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April 30, 2018 16:10 ET (20:10 GMT)