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Press Release: Novartis investigational BYL719 (alpelisib) plus fulvestrant consistently improved PFS in patients with PIK3CA mutated HR+/HER2- advanced brea...

Novartis International AG / Novartis investigational BYL719 (alpelisib)

plus fulvestrant consistently improved PFS in patients with PIK3CA

mutated HR+/HER2- advanced breast cancer in new SOLAR-1 analyses.

Processed and transmitted by West Corporation. The issuer is solely

responsible for the content of this announcement.

-- BYL719 plus fulvestrant meaningfully prolonged PFS vs fulvestrant alone

in patients with PIK3CA mutated HR+/HER2- advanced breast cancer after

progression on an aromatase inhibitor or after receiving up to one

additional line of therapy[1]

-- SOLAR-1 is the first Phase III breast cancer trial to demonstrate

potential viability of using liquid biopsy to select patients for

targeted treatment[1]

-- Novartis continues to invest in flexible genomic profiling solutions to

identify the approximately 40% of HR+ advanced breast cancer patients

with a PIK3CA mutation who may benefit from targeted therapy[2]

Basel, December 6, 2018 - Novartis today announced additional analysis

from the global Phase III SOLAR-1 trial investigating the alpha-specific

PI3K inhibitor BYL719 (alpelisib) in combination with fulvestrant in men

and postmenopausal women with PIK3CA mutated hormone receptor positive,

human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced

or metastatic breast cancer.

In SOLAR-1, the addition of BYL719 to fulvestrant nearly doubled median

progression-free survival (PFS) in patients with PIK3CA mutated

HR+/HER2- advanced breast cancer who progressed on or after an aromatase

inhibitor (AI) compared to fulvestrant alone. In this analysis, BYL719

plus fulvestrant also showed consistent clinically meaningful treatment

benefit after progression on an AI or after receiving up to one

additional line of therapy for advanced breast cancer[1]. These data

will be presented today during an oral presentation at the 2018 San

Antonio Breast Cancer Symposium (SABCS) (Abstract #GS3-08).

Approximately 40% of patients living with HR+ advanced breast cancer

have a PIK3CA mutation, which over activates the PI3K pathway[2]. When

activated, the PI3K pathway is associated with tumor growth, resistance

to endocrine treatment and a poor overall prognosis[3],[4]. Currently

there are no approved treatments for breast cancer that specifically

target this mutation.

"PIK3CA mutation is the most common actionable alteration in ER+ breast

cancer, so it is encouraging to see a meaningfully prolonged PFS with

BYL719 combination therapy in patients with PIK3CA mutated breast cancer

who progressed on an aromatase inhibitor and who received up to one

additional line of therapy prior to treatment with BYL719 plus

fulvestrant," said Dejan Juric, MD, Director, Termeer Center for

Targeted Therapies, Massachusetts General Hospital Cancer Center. "With

the SOLAR-1 trial results, we can confidently say that identifying and

targeting PIK3CA mutations is clinically important as we apply the

precision oncology paradigm to breast cancer and continuously look for

new treatment solutions to extend the lives of patients with this

disease."

BYL719 in combination with fulvestrant consistently improved median PFS

in patients with PIK3CA mutated HR+/HER2- advanced breast cancer who

progressed within 12 months of AI treatment (mPFS: 11.0 months vs 6.8

months for fulvestrant alone) or received up to one additional line of

therapy for advanced breast cancer (mPFS: 10.9 months vs 3.7 months,

respectively).

Most adverse events were mild to moderate in severity and generally

manageable through dose interruption, dose reductions and medical

management. Treatment discontinuation rate due to adverse events in

those with a PIK3CA mutation receiving BYL719 plus fulvestrant was 3%

compared to 2% for fulvestrant alone. The most frequent all-grade

adverse events (>=40%) were hyperglycemia (65% vs 9%), diarrhea (54% vs

11%), nausea (46% vs 20%) and rash (40% vs 6%). The most common grade

3/4 events (>=10%) were hyperglycemia (37% vs <1%) and rash (13% vs

<1%)[1].

Mutation status of participants in SOLAR-1 was identified by a clinical

trial assay developed by Qiagen(*). A significant PFS benefit was

observed for BYL719 plus fulvestrant in patients with a PIK3CA mutation

regardless of whether the mutation was identified by a tumor tissue test

or ctDNA test, suggesting the potential viability of using liquid

biopsies to identify PIK3CA mutation status (tissue positive HR=0.65;

mPFS 11.0 months; plasma positive HR=0.56; mPFS 10.9 months)[1].

Novartis has entered into agreements with both Qiagen and Foundation

Medicine(**) to develop flexible companion diagnostic solutions for

BYL719 that utilize both tumor tissue and plasma sample types.

"Our work to develop an effective PI3K inhibitor started more than two

decades ago, and learning from multiple clinical trial experiences, we

have been able to advance an investigational targeted therapy for

patients with this specific breast cancer," said Samit Hirawat, MD, Head,

Novartis Oncology Global Drug Development. "SOLAR-1 is the first breast

cancer trial to show potential utility of liquid biopsies. We are

excited to collaborate with Qiagen and Foundation Medicine on tissue and

plasma tests that, if approved, may help oncologists identify patients

who could benefit from BYL719 plus fulvestrant."

The SOLAR-1 trial is ongoing to evaluate secondary endpoints, including

overall survival and will be presented and discussed in the future.

Overall survival (OS) results were immature at the time of data cut-off

after 52% of events (HR=0.73; 95% CI 0.48-1.10; p=0.06; median not

estimable vs 26.9 months). The prespecified O'Brien-Fleming stopping

boundary was not crossed. Discussions with health authorities regarding

the SOLAR-1 data have begun.

About SOLAR-1

SOLAR-1 is a global, Phase III randomized, double-blind,

placebo-controlled trial studying investigational BYL719 in combination

with fulvestrant for postmenopausal women with PIK3CA-mutated HR+/HER2-

advanced or metastatic breast cancer that progressed on or following

aromatase inhibitor treatment with or without a CDK4/6 inhibitor[1].

The trial randomized 572 patients. Patients were allocated based on

tumor tissue assessment to either a PIK3CA-mutated cohort or a PIK3CA

non-mutated cohort. Within each cohort, patients were randomized in a

1:1 ratio to receive continuous oral treatment with BYL719 (300mg once

daily) plus fulvestrant (500 mg every 28 days + Cycle 1 Day 15) or

placebo plus fulvestrant. Stratification was based on visceral

metastases and prior CDK4/6 inhibitor treatment[1].

The primary endpoint is local investigator assessed PFS using RECIST 1.1

for patients with a PIK3CA mutation. Secondary endpoints include but are

not limited to overall survival, overall response rate, clinical benefit

rate, health-related quality of life, efficacy in PIK3CA non-mutated

cohort, safety and tolerability[1].

For the primary SOLAR-1 analysis, mutation status was determined by

tumor tissue via polymerase chain reaction (PCR) analysis. Plasma ctDNA

samples were also collected at baseline as a secondary endpoint. Plasma

ctDNA mutation status of participants in SOLAR-1 was identified by an

assay developed by Qiagen.

About BYL719 (alpelisib)

BYL719 is an investigational, orally bioavailable, alpha-specific PI3K

inhibitor. In breast cancer cell lines harboring PIK3CA mutations,

BYL719 has been shown to potentially inhibit the PI3K pathway and have

antiproliferative effects. In addition, cancer cell lines with PIK3CA

mutations were more sensitive to BYL719 than those without the mutation

across a broad range of different cancers[5].

About Novartis in Advanced Breast Cancer

For more than 30 years, Novartis has been tackling breast cancer with

superior science, great collaboration and a passion for transforming

patient care. With one of the most diverse breast cancer pipelines and

one of the largest numbers of breast cancer compounds in development,

Novartis leads the industry in discovery of new therapies and

combinations, especially in HR+ advanced breast cancer, the most common

form of the disease.

Disclaimer

This press release contains forward-looking statements within the

meaning of the United States Private Securities Litigation Reform Act of

1995. Forward-looking statements can generally be identified by words

such as "potential," "can," "will," "plan," "expect," "anticipate,"

"look forward," "believe," "committed," "investigational," "pipeline,"

"launch," "encouraging," or similar terms, or by express or implied

discussions regarding potential marketing approvals, new indications or

labeling for BYL719 or the other investigational or approved products

described in this press release, or regarding potential future revenues

from such products. You should not place undue reliance on these

statements. Such forward-looking statements are based on our current

beliefs and expectations regarding future events, and are subject to

significant known and unknown risks and uncertainties. Should one or

more of these risks or uncertainties materialize, or should underlying

assumptions prove incorrect, actual results may vary materially from

those set forth in the forward-looking statements. There can be no

guarantee that BYL719 or the other investigational or approved products

described in this press release will be submitted or approved for sale

or for any additional indications or labeling in any market, or at any

particular time. Nor can there be any guarantee that BYL719 or such

other products will be commercially successful in the future. In

particular, our expectations regarding BYL719 and such other products

could be affected by, among other things, the uncertainties inherent in

research and development, including clinical trial results and

additional analysis of existing clinical data; regulatory actions or

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