LYNPARZA Receives Additional and Broad Approval in the U.S. for Ovarian Cancer

LYNPARZA’s New Tablet Formulation Approved as Maintenance Treatment
for Women With Platinum-Sensitive Recurrent Ovarian Cancer Regardless of
BRCA-Mutation Status

LYNPARZA Tablets Also Indicated in BRCA-Mutated Ovarian Cancer Beyond
the Third-Line Setting

Newly-Approved Tablet Formulation Means Improved Patient Convenience

KENILWORTH, N.J.–(BUSINESS WIRE)–$MRK #MRK–AstraZeneca and Merck & Co., Inc. (NYSE:MRK), known as MSD outside the
United States and Canada, today announced that the U.S. Food and Drug
Administration (FDA) has granted approval for the PARP inhibitor,
LYNPARZA (olaparib), as follows:

  • New use of LYNPARZA as a maintenance treatment for recurrent,
    epithelial ovarian, fallopian tube or primary peritoneal adult cancer
    who are in response to platinum-based chemotherapy, regardless of BRCA
    status;
  • New use of LYNPARZA tablets (2 tablets twice daily) as opposed to
    capsules (8 capsules twice daily);
  • LYNPARZA tablets also now indicated (conversion from the current
    accelerated approval) for the use in patients with deleterious or
    suspected deleterious germline BRCA-mutated advanced ovarian cancer,
    who have been treated with three or more prior lines of chemotherapy.

Sean Bohen, executive vice president, global medicines development and
chief medical officer of AstraZeneca, said: “Physicians have almost
three years of clinical experience with LYNPARZA on the market and we
are now pleased to bring this important medicine, in a new tablet
formulation, to a broader group of women. Today’s approvals validate
more than 10 years of dedicated research behind LYNPARZA, the world’s
first PARP inhibitor, which now provides oncologists with the greater
flexibility for use in terms of treatment settings. It builds on our
recently-announced collaboration with Merck, which aims to further
increase the number of treatment options available to patients.”

Eric Pujade-Lauraine, head of the women cancers and clinical research
department at Hôpitaux Universitaires Paris Centre, site Hôtel-Dieu,
AP-HP and principal investigator of the SOLO-2 trial, one of the trials
supporting the approval, said: “Today’s approval is welcome news for
U.S. patients with ovarian cancer, who are now able to benefit from
treatment with olaparib irrespective of their BRCA-mutation status. This
latest regulatory milestone underscores the breadth and depth of
clinical data on olaparib, and not only demonstrates its efficacy as
maintenance therapy, but adds to the data presented earlier this year
showing sustained quality of life for patients undergoing treatment for
this serious disease.”

Roger M. Perlmutter, president of Merck Research Laboratories, said: “We
congratulate AstraZeneca on the approval of these new indications and
the new dosage form and schedule for LYNPARZA, an important therapeutic
advance for many patients with ovarian cancer. This is a significant
first regulatory event in our collaboration with AstraZeneca. We look
forward to working with AstraZeneca in our global collaboration to bring
this medicine with its new indications to patients.”

Two randomized trials supported the new approvals and the conversion of
accelerated approval to full approval which was originally based on a
single-arm trial:

  • SOLO-2 (n=295) confirmed the benefit of LYNPARZA in germline
    BRCA-mutated (gBRCAm) patients, demonstrating a 70% reduced risk of
    disease progression or death (HR 0.30 [95% CI, 0.22-0.41], P<0.0001) and improved progression-free survival (PFS) to 19.1 vs 5.5 months for placebo by investigator-assessed analysis.
  • Study 19 (n=265) showed that LYNPARZA reduced the risk of disease
    progression or death by 65% and improved PFS compared with placebo in
    patients of any BRCA status (HR 0.35 [95% CI, 0.25-0.49], P<0.0001; median PFS of 8.4 months vs 4.8 months for placebo). Additionally, patients in Study 19, treated with LYNPARZA as a maintenance therapy, had a median overall survival (OS) of 29.8 months vs 27.8 months for placebo (HR 0.73 [95% CI, 0.55-0.95]).

Table 1. Summary of key efficacy results from randomized trials:

Analysis      

Reduction in the risk of
disease progression or death
(PFS)

     

Reduction in the risk of
death (OS)

SOLO-2
[gBRCAm]

   

LYNPARZA

     

70% (HR 0.30 [95% CI, 0.22-
0.41], P<0.0001)

      Data not yet mature
    Placebo            

Study 19
[PSR OC*]

LYNPARZA

65% (HR 0.35 [95% CI, 0.25-
0.49], P<0.0001)

27% (HR 0.73 [95% CI,
0.55-0.95]

    Placebo            

*PSR = Platinum-sensitive recurrent ovarian cancer

 

The most-common adverse events reported in 20% or more of patients
across the SOLO-2 trial in the LYNPARZA arm were anaemia (44%), nausea
(76%), vomiting (37%), diarrhoea (33%), fatigue/asthenia (66%),
decreased appetite (22%), headache (25%), and dysgeusia (27%). The
most-common Grade 3 or 4 adverse events were anaemia (20%), nausea
(2.6%), vomiting (2.6%), diarrhoea (1.0%), fatigue/asthenia (4.1%), and
headache (0.5%). Discontinuation of LYNPARZA resulting from adverse
events was seen in 11% of patients. Dose interruptions of LYNPARZA due
to an adverse reaction of any grade was 45%. Dose reductions of LYNPARZA
due to an adverse reaction was 25%.

The most-common adverse events reported in 20% or more of patients
across the Study 19 trial in the LYNPARZA arm were anaemia (23%), nausea
(71%), vomiting (35%), diarrhoea (27%), fatigue (including asthenia)
(63%), decreased appetite (21%), and headache (21%). The most-common
Grade 3 or 4 adverse events were anaemia (7.4%), nausea (2.2%), vomiting
(2.2%), diarrhoea (2.2%), and fatigue (including asthenia) (8.8%).
Discontinuation of LYNPARZA resulting from adverse events was seen in 4%
of patients. Dose interruptions of LYNPARZA due to an adverse reaction
of any grade was 25%. Dose reductions of LYNPARZA due to an adverse
reaction was 15%.

The full data from the SOLO-2 trial can be found in the July 25, 2017
publication of The Lancet Oncology.

LYNPARZA was first approved under the FDA’s Accelerated Approval program
in December 2014, as a capsule formulation, making it the first poly
ADP-ribose polymerase (PARP) inhibitor approved. Since then, more than
3,000 advanced ovarian cancer patients have been treated with LYNPARZA
capsules in its approved indication.

About SOLO-2

SOLO-2 was a Phase III, randomized, double-blinded, multicenter trial
designed to determine the efficacy of LYNPARZA tablets as a maintenance
monotherapy compared with placebo, in patients with platinum-sensitive,
relapsed or recurrent gBRCA-mutated ovarian, fallopian tube and primary
peritoneal cancer. The trial, conducted in collaboration with the
European Network for Gynaecological Oncological Trial Groups (ENGOT) and
Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et
du sein (GINECO), randomised 295 patients with documented germline BRCA1
or BRCA2 mutations who had received at least 2 prior lines of
platinum-based chemotherapy and were in complete or partial response.
Eligible patients were randomized to receive 300mg LYNPARZA tablets
twice daily or placebo tablets twice daily.

About Study 19

Study 19 was a Phase II, randomized, double-blinded, placebo-controlled,
multicenter trial, which evaluated the efficacy and safety of LYNPARZA
compared with placebo in relapsed, high-grade serous ovarian cancer
patients, involving 82 sites across 16 countries. Patients received
LYNPARZA maintenance monotherapy, at a dose of 400mg per day or matching
placebo. Treatment continued until disease progression if toxicities
were manageable.

About LYNPARZA

LYNPARZA is an innovative, first-in-class oral poly ADP-ribose
polymerase (PARP) inhibitor that may exploit tumor DNA damage response
(DDR) pathway deficiencies to preferentially kill cancer cells. It is
approved by regulatory authorities in the EU and US for the treatment of
women with BRCAm ovarian cancer. LYNPARZA tablets are currently being
tested in combinations in a range of tumor types including breast,
prostate, and pancreatic cancers.

About the AstraZeneca and Merck Strategic Oncology Collaboration

On July 27, 2017, AstraZeneca and Merck & Co., Inc. announced a global
strategic oncology collaboration to co-develop and co-commercialize
AstraZeneca’s LYNPARZA, the world’s first and leading PARP inhibitor,
and potential new medicine selumetinib, a MEK inhibitor, for multiple
cancer types. The collaboration is based on increasing evidence that
PARP and MEK inhibitors can be combined with PDL-1/PD-1 inhibitors for a
range of tumor types. Working together, the companies will jointly
develop LYNPARZA and selumetinib in combination with other potential new
medicines and as a monotherapy. Independently, the companies will
develop LYNPARZA and selumetinib in combination with their respective
PD-L1 and PD-1 medicines.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck, helping people
fight cancer is our passion and supporting accessibility to our cancer
medicines is our commitment. Our focus is on pursuing research in
immuno-oncology and we are accelerating every step in the journey – from
lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the fastest-growing development
programs in the industry. We are currently executing an expansive
research program that includes more than 500 clinical trials evaluating
our anti-PD-1 therapy across more than 30 tumor types. We also continue
to strengthen our immuno-oncology portfolio through strategic
acquisitions and are prioritizing the development of several promising
immunotherapeutic candidates with the potential to improve the treatment
of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For more than a century, Merck, a leading global biopharmaceutical
company known as MSD outside of the United States and Canada, has been
inventing for life, bringing forward medicines and vaccines for many of
the world’s most challenging diseases. Through our prescription
medicines, vaccines, biologic therapies and animal health products, we
work with customers and operate in more than 140 countries to deliver
innovative health solutions. We also demonstrate our commitment to
increasing access to health care through far-reaching policies, programs
and partnerships. Today, Merck continues to be at the forefront of
research to advance the prevention and treatment of diseases that
threaten people and communities around the world – including cancer,
cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease
and infectious diseases including HIV and Ebola. For more information,
visit www.merck.com and connect
with us on TwitterFacebookInstagramYouTube and LinkedIn.

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