On February 2, 2017 Amgen (NASDAQ:AMGN) reported financial results for the fourth quarter and full year of 2016 (Press release, Amgen, FEB 2, 2017, View Source [SID1234517628]).

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Key results include:

For the fourth quarter, total revenues increased 8 percent versus the fourth quarter of 2015 to $6.0 billion.
Product sales grew 6 percent driven by Enbrel (etanercept), Prolia (denosumab), Repatha (evolocumab) and KYPROLIS (carfilzomib).
For the full year, total revenues increased 6 percent to $23.0 billion, with 5 percent product sales growth.
GAAP earnings per share (EPS) increased 9 percent in the fourth quarter to $2.59 and 13 percent for the full year to $10.24, driven by higher revenues and higher operating margins.
GAAP operating income increased 22 percent in the fourth quarter to $2.5 billion and 16 percent for the full year to $9.8 billion.
Non-GAAP EPS increased 11 percent in the fourth quarter to $2.89 and 12 percent for the full year to $11.65, driven by higher revenues and higher operating margins.
Non-GAAP operating income increased 21 percent in the fourth quarter to $2.9 billion and 14 percent for the full year to $11.4 billion.
2017 total revenues guidance of $22.3-$23.1 billion; EPS guidance of $10.45-$11.31 on a GAAP basis and $11.80-$12.60 on a non-GAAP basis.
The Company generated $9.6 billion of free cash flow for the full year versus $9.1 billion in 2015 driven by higher net income.
"We finished the year with strong operating performance," said Robert A. Bradway, chairman and chief executive officer. "We anticipate several new product development opportunities and launches in 2017, and are excited about the Repatha cardiovascular outcomes data we released today. We have established a firm foundation for longer-term growth."



$Millions, except EPS and percentages

Q4’16

Q4’15

YOY Δ

FY ’16

FY ’15

YOY Δ













Total Revenues

$ 5,965

$ 5,536

8%

$ 22,991

$ 21,662

6%
GAAP Operating Income

$ 2,485

$ 2,033

22%

$ 9,794

$ 8,470

16%
GAAP Net Income

$ 1,935

$ 1,800

8%

$ 7,722

$ 6,939

11%
GAAP EPS

$ 2.59

$ 2.37

9%

$ 10.24

$ 9.06

13%
Non-GAAP Operating Income

$ 2,859

$ 2,366

21%

$ 11,446

$ 10,052

14%
Non-GAAP Net Income

$ 2,160

$ 1,985

9%

$ 8,785

$ 7,954

10%
Non-GAAP EPS

$ 2.89

$ 2.61

11%

$ 11.65

$ 10.38

12%

References in this release to "non-GAAP" measures, measures presented "on a non-GAAP basis" and to "free cash flow" (computed by subtracting capital expenditures from operating cash flow) refer to non-GAAP financial measures. Adjustments to the most directly comparable GAAP financial measures and other items are presented on the attached reconciliations.



Product Sales Performance

Total product sales increased 6 percent for the fourth quarter of 2016 versus the fourth quarter of 2015. The increase was driven primarily by ENBREL, Prolia, Repatha and KYPROLIS. Product sales increased 5 percent for the full year.
ENBREL sales increased 14 percent for the fourth quarter driven by net selling price and favorable changes in inventory levels, offset partially by the impact of competition. Sales increased 11 percent for the full year driven by net selling price, offset partially by the impact of competition.
Neulasta (pegfilgrastim) sales decreased 3 percent for the fourth quarter and 1 percent for the full year driven by lower unit demand.
Aranesp (darbepoetin alfa) sales increased 5 percent for the fourth quarter and 7 percent for the full year driven by higher unit demand due to a shift by some U.S. dialysis customers from EPOGEN (epoetin alfa) to Aranesp, offset partially by unfavorable changes in net selling price.
Prolia sales increased 22 percent for the fourth quarter and 25 percent for the full year driven by higher unit demand.
Sensipar/Mimpara (cinacalcet) sales increased 7 percent for the fourth quarter driven by net selling price. Sales increased 12 percent for the full year driven by net selling price and higher unit demand.
XGEVA (denosumab) sales increased 6 percent for the fourth quarter and 9 percent for the full year driven by higher unit demand.
EPOGEN sales decreased 8 percent for the fourth quarter and 31 percent for the full year driven by the impact of competition and a shift by some U.S. dialysis customers to Aranesp.
KYPROLIS sales increased 24 percent for the fourth quarter and 35 percent for the full year driven by higher unit demand.
NEUPOGEN (filgrastim) sales decreased 34 percent for the fourth quarter and 27 percent for the full year driven primarily by the impact of competition in the U.S.
Nplate (romiplostim) sales increased 9 percent for the fourth quarter and 11 percent for the full year driven by higher unit demand.
Vectibix (panitumumab) sales increased 6 percent for the fourth quarter and 11 percent for the full year driven by higher unit demand.
Repatha sales growth for the fourth quarter and full year was driven by higher unit demand.
BLINCYTO (blinatumomab) sales increased 32 percent for the fourth quarter and 49 percent for the full year driven by higher unit demand.


Product Sales Detail by Product and Geographic Region









$Millions, except percentages

Q4’16

Q4’15

YOY Δ


US
ROW
TOTAL

TOTAL

TOTAL









Enbrel

$1,582
$62
$1,644

$1,441

14%
Neulasta

943
173
1,116

1,156

(3%)
Aranesp

286
240
526

499

5%
Prolia

293
170
463

380

22%
Sensipar / Mimpara

330
81
411

384

7%
XGEVA

273
103
376

356

6%
EPOGEN

316
0
316

342

(8%)
KYPROLIS

143
40
183

148

24%
NEUPOGEN

116
57
173

263

(34%)
Nplate

88
62
150

137

9%
Vectibix

57
86
143

135

6%
Repatha
36
22
58

7

*
BLINCYTO
24
5
29

22

32%
Other**

19
56
75

59

27%









Total product sales

$4,506
$1,157
$5,663

$5,329

6%









* Change in excess of 100%




** Other includes MN Pharma, Bergamo, IMLYGICand Corlanor















































$Millions, except percentages

FY ’16

FY ’15

YOY Δ


US
ROW
TOTAL

TOTAL

TOTAL









Enbrel

$5,719
$246
$5,965

$5,364

11%
Neulasta

3,925
723
4,648

4,715

(1%)
Aranesp

1,082
1,011
2,093

1,951

7%
Prolia

1,049
586
1,635

1,312

25%
Sensipar / Mimpara

1,240
342
1,582

1,415

12%
XGEVA

1,115
414
1,529

1,405

9%
EPOGEN

1,282
0
1,282

1,856

(31%)
NEUPOGEN

534
231
765

1,049

(27%)
KYPROLIS

554
138
692

512

35%
Vectibix

229
382
611

549

11%
Nplate

350
234
584

525

11%
Repatha

101
40
141

10

*
BLINCYTO

85
30
115

77

49%
Other**

60
190
250

204

23%









Total product sales

$17,325
$4,567
$21,892

$20,944

5%


















* Change in excess of 100%



** Other includes MN Pharma, Bergamo, IMLYGICand Corlanor

Operating Expense, Operating Margin and Tax Rate Analysis

On a GAAP basis:

Total Operating Expenses decreased 1 percent in the fourth quarter and were flat for the full year, with all expense categories reflecting savings from our transformation and process improvement efforts. Cost of Sales margin improved by 1.3 percentage points in the fourth quarter and 1.2 percentage points for the full year driven primarily by manufacturing efficiencies. Research & Development (R&D) expenses were flat for the fourth quarter. For the full year, R&D expenses decreased 6 percent driven primarily by lower spending required to support certain later-stage clinical programs and transformation and process improvement efforts, offset partially by external business development activities. Selling, General & Administrative (SG&A) expenses decreased 7 percent in the fourth quarter due to the Oct. 31, 2016, expiration of ENBREL residual royalty payments. For the full year, SG&A expenses increased 4 percent driven primarily by investments in new product launches, offset partially by the expiration of ENBREL residual royalty payments. Other expenses increased in the fourth quarter and for the full year as the prior year periods included gains from the sale of assets related to our site closures.
Operating Margin improved by 5.8 percentage points in the fourth quarter to 43.9 percent, and 4.3 percentage points for the full year to 44.7 percent.
Tax Rate for the fourth quarter increased 9.3 percentage points driven primarily by changes in the geographic mix of earnings and the discrete impact of the enactment of the federal R&D credit in the fourth quarter of 2015. The full year tax rate increased 2.7 percentage points driven by changes in the geographic mix of earnings, offset partially by the benefit of adopting Accounting Standards Update 2016-09, Improvements to Employee Share-Based Payment Accounting (ASU 2016-09).
On a non-GAAP basis:

Total Operating Expenses decreased 2 percent in the fourth quarter and 1 percent for the full year, with all expense categories reflecting savings from our transformation and process improvement efforts. Cost of Sales margin improved by 1.0 percentage points in the fourth quarter and 1.2 percentage points for the full year driven primarily by manufacturing efficiencies. R&D expenses were flat in the fourth quarter. For the full year, R&D expenses decreased 4 percent driven primarily by lower spending required to support certain later-stage clinical programs and transformation and process improvement efforts, offset partially by external business development activities. SG&A expenses decreased 4 percent in the fourth quarter due to the Oct. 31, 2016, expiration of ENBREL residual royalty payments. For the full year, SG&A expenses increased 5 percent driven primarily by investments in new product launches, offset partially by the expiration of ENBREL residual royalty payments.
Operating Margin improved by 6.1 percentage points in the fourth quarter to 50.5 percent, and 4.3 percentage points for the year to 52.3 percent.
Tax Rate for the fourth quarter increased 7.1 percentage points driven primarily by changes in the geographic mix of earnings and the discrete impact of the enactment of the federal R&D credit in the fourth quarter of 2015. The full year tax rate increased 2.0 percentage points driven by changes in the geographic mix of earnings, offset partially by the benefit of adopting ASU 2016-09.

















$Millions, except percentages












GAAP

Non-GAAP




Q4’16

Q4’15

YOY Δ

Q4’16

Q4’15

YOY Δ















Cost of Sales
$1,067

$1,071

(0%)

$753

$764

(1%)


% of product sales
18.8%

20.1%

(1.3) pts

13.3%

14.3%

(1) pts
Research & Development
$1,078

$1,093

(1%)

$1,056

$1,057

0%


% of product sales
19.0%

20.5%

(1.5) pts

18.6%

19.8%

(1.2) pts
Selling, General & Administrative
$1,323

$1,416

(7%)

$1,297

$1,349

(4%)


% of product sales
23.4%

26.6%

(3.2) pts

22.9%

25.3%

(2.4) pts
Other
$12

($77)

*

$0

$0

0%
TOTAL Operating Expenses
$3,480

$3,503

(1%)

$3,106

$3,170

(2%)















Operating Margin













operating income as a % of product sales
43.9%

38.1%

5.8 pts

50.5%

44.4%

6.1 pts















Tax Rate
15.2%

5.9%

9.3 pts

18.7%

11.6%

7.1 pts















* Change in excess of 100%










pts: percentage points




































































$Millions, except percentages











GAAP

Non-GAAP




FY ’16

FY ’15

YOY Δ

FY ’16

FY ’15

YOY Δ















Cost of Sales
$4,162

$4,227

(2%)

$2,913

$3,033

(4%)


% of product sales
19.0%

20.2%

(1.2) pts

13.3%

14.5%

(1.2) pts
Research & Development
$3,840

$4,070

(6%)

$3,755

$3,917

(4%)


% of product sales
17.5%

19.4%

(1.9) pts

17.2%

18.7%

(1.5) pts
Selling, General & Administrative
$5,062

$4,846

4%

$4,877

$4,660

5%


% of product sales
23.1%

23.1%

0 pts

22.3%

22.2%

0.1 pts
Other
$133

$49

*

$0

$0

0%
TOTAL Operating Expenses
$13,197

$13,192

0%

$11,545

$11,610

(1%)















Operating Margin













operating income as a % of product sales
44.7%

40.4%

4.3 pts

52.3%

48.0%

4.3 pts















Tax Rate
15.7%

13.0%

2.7 pts

18.8%

16.8%

2 pts















* Change in excess of 100%










pts: percentage points


























Cash Flow and Balance Sheet

The Company generated $2.9 billion of free cash flow in the fourth quarter of 2016 versus $1.9 billion in the fourth quarter of 2015 due primarily to the timing of tax and other payments, as well as higher net income. The Company generated $9.6 billion of free cash flow in 2016 versus $9.1 billion in 2015 due to higher net income.
The Company’s first quarter 2017 dividend of $1.15 per share declared on Dec. 20, 2016, will be paid on March 8, 2017, to all stockholders of record as of Feb. 15, 2017. This represents a 15 percent increase from that paid in each of the previous four quarters.
During the fourth quarter, the Company repurchased 6.7 million shares of common stock at a total cost of $1.0 billion. For the full year, the Company repurchased 19.7 million shares of common stock at a total cost of $3.0 billion. At the end of 2016, the Company had $4.1 billion remaining under its stock repurchase authorization.

















$Billions, except shares
Q4’16

Q4’15

YOY Δ

FY ’16

FY ’15

YOY Δ















Operating Cash Flow
$3.1

$2.1

$1.0

$10.4

$9.7

$0.6
Capital Expenditures
0.2

0.2

0.0

0.7

0.6

0.1
Free Cash Flow
2.9

1.9

1.0

9.6

9.1

0.5
Dividends Paid
0.7

0.6

0.2

3.0

2.4

0.6
Share Repurchase
1.0

0.2

0.8

3.0

1.9

1.1
Avg. Diluted Shares (millions)
748

761

(13)

754

766

(12)















Cash and Investments
38.1

31.4

6.7

38.1

31.4

6.7
Debt Outstanding
34.6

31.4

3.2

34.6

31.4

3.2
Stockholders’ Equity
29.9

28.1

1.8

29.9

28.1

1.8

















Note: Numbers may not add due to rounding






2017 Guidance

For the full year 2017, the Company expects:

Total revenues in the range of $22.3 billion to $23.1 billion.
On a GAAP basis, EPS in the range of $10.45 to $11.31 and a tax rate in the range of 16 percent to 18 percent.
On a non-GAAP basis, EPS in the range of $11.80 to $12.60 and a tax rate in the range of 18.5 percent to 19.5 percent.
Capital expenditures to be approximately $700 million.
Share repurchases of approximately $2.5 billion to $3.5 billion.



Fourth Quarter Product and Pipeline Update
Key development milestones:



Clinical Program
Indication
Projected Milestone
Repatha
Hyperlipidemia
Phase 3 CV outcomes data presentation Q1 2017*
KYPROLIS
Relapsed or refractory
multiple myeloma
Phase 3 study initiation with DARZALEX
XGEVA
Prevention of SREs in
multiple myeloma
Global regulatory submissions
BLINCYTO
Diffuse large B-cell
lymphoma
Phase 2/3 study initiations
EVENITY (romosozumab)†
Postmenopausal
osteoporosis
U.S. regulatory review
Active controlled Phase 3 fracture data Q2 2017*
Erenumab (AMG 334)
Migraine prophylaxis
Global regulatory submissions
Parsabiv (etelcalcetide)†
Secondary
hyperparathyroidism
U.S. regulatory review
ABP 215
(biosimilar bevacizumab)
Oncology
Global regulatory reviews
ABP 501
(biosimilar adalimumab)
Inflammatory diseases
Ex-U.S. regulatory reviews
ABP 980
(biosimilar trastuzumab)
Breast cancer
Global regulatory submissions
*Event driven study; †Trade name provisionally approved by FDA; CV = cardiovascular; SRE =
skeletal-related event

The Company provided the following updates on selected product and pipeline programs:

Repatha

In December, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for an extension to the marketing authorization of a new 420 mg single-dose delivery option.
Data from a Phase 3 study evaluating the effects of Repatha on cardiovascular outcomes that met its primary composite endpoint and key secondary composite endpoint will be presented at the American College of Cardiology 66th Annual Scientific Session on March 17.
Omecamtiv mecarbil

Enrollment of the Phase 3 cardiovascular outcomes study in chronic heart failure patients commenced in Q1 2017.
KYPROLIS

The primary endpoint in a Phase 3 study of once weekly KYPROLIS administration in relapsed and refractory multiple myeloma patients (ARROW) has been modified from overall response rate to progression-free survival, an event driven endpoint, with results expected in 2019.
In November, a collaboration was established with Janssen Biotech, Inc. (Janssen) to evaluate the combination of KYPROLIS and Janssen’s DARZALEX (daratumumab) in multiple clinical studies in patients with multiple myeloma.
A Phase 3 registrational study evaluating KYPROLIS in combination with DARZALEX and dexamethasone compared to KYPROLIS and dexamethasone alone in patients with multiple myeloma who have had one, two or three prior lines of therapy is anticipated to begin enrollment in Q2 2017.
XGEVA

Regulatory submissions for the prevention of skeletal-related events in multiple myeloma patients are expected in 2017.
BLINCYTO

Regulatory submissions for Philadelphia chromosome-positive relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL) are expected in 2017. BLINCYTO is currently approved for the treatment of adult and pediatric patients with Philadelphia chromosome-negative R/R B-cell precursor ALL.
Phase 2/3 studies in patients with diffuse large B-cell lymphoma will enroll patients in 2017.
EVENITY (romosozumab)

In December, an application for marketing approval for the treatment of osteoporosis for men and women at high risk for fracture was submitted to the Pharmaceuticals and Medical Devices Agency in Japan. This follows the postmenopausal osteoporosis U.S. filing in 2016 with a U.S. Food and Drug Administration (FDA) Prescription Drug User Fee Act (PDUFA) target action date of July 19, 2017.
Primary results from an event driven active controlled Phase 3 fracture study (ARCH) in postmenopausal women with osteoporosis are expected in Q2 2017.
Erenumab

In November, a second Phase 3 study met its primary endpoint, demonstrating statistically significant reductions from baseline in monthly migraine days in patients with episodic migraine treated with either 70 mg or 140 mg erenumab compared with placebo.
Regulatory submissions for the prevention of episodic and chronic migraine are expected in Q2 2017.
CNP520

In December, FDA granted fast track designation to CNP520, a small molecule beta-site amyloid precursor protein-cleaving enzyme-1 (BACE) inhibitor for the potential treatment of Alzheimer’s disease.
Parsabiv

FDA has set a Feb. 9, 2017, PDUFA target action date for the review of Parsabiv for the treatment of secondary hyperparathyroidism (sHPT) in adult patients with chronic kidney disease (CKD) on hemodialysis.
In November, the EMA granted marketing authorization for the treatment of sHPT in adult patients with CKD on hemodialysis.
ENBREL

In November, FDA approved the supplemental Biologics License Application (BLA) for the expanded use to treat pediatric patients (ages 4-17) with chronic moderate-to-severe plaque psoriasis.
ABP 215 (biosimilar bevacizumab)

In January 2017, a BLA was accepted by FDA with a Sept. 14, 2017, Biosimilar User Fee target action date.
In December, a Marketing Authorization Application was submitted to the EMA.
ABP 501 (biosimilar adalimumab)

In January 2017, the CHMP adopted a positive opinion for the Marketing Authorization of ABP 501, recommending approval for all available indications. ABP 501 has been recommended for approval for the treatment of certain inflammatory diseases in adults, including moderate-to-severe rheumatoid arthritis, psoriatic arthritis, severe ankylosing spondylitis (AS), severe axial spondyloarthritis without radiographic evidence of AS, moderate-to-severe chronic plaque psoriasis, moderate-to-severe hidradenitis suppurativa, non-infectious intermediate, posterior and panuveitis, moderate-to-severe Crohn’s disease and moderate-to-severe ulcerative colitis. The CHMP opinion also recommends approval for the treatment of certain pediatric inflammatory diseases, including moderate-to-severe Crohn’s disease (ages six and older), severe chronic plaque psoriasis (ages four and older), enthesitis-related arthritis (ages six and older) and polyarticular juvenile idiopathic arthritis (ages two and older).


Erenumab and CNP520 are developed in collaboration with Novartis AG
Omecamtiv mecarbil is developed in collaboration with Cytokinetics and in an alliance with Servier for certain territories.
EVENITY is developed in collaboration with UCB globally, as well as our joint venture partner Astellas in Japan
DARZALEX is a registered trademark of Janssen Biotech, Inc.

On February 2, 2017 AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three main therapy areas – respiratory, inflammation, autoimmune disease (RIA), cardiovascular and metabolic disease (CVMD) and oncology – as well as in infection and neuroscience reported financial results for the fourth quarter and full-year of 2016 (Press release, AstraZeneca, FEB 2, 2017, View Source [SID1234517638]).

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Total worldwide product sales for the forth quarter of 2016 was $ 5,260 m USD in comparison to that of $6,207 m USD for the forth quarter of 2015. Total worldwide product sales for the fiscal year ended December 31, 2016 was $21,319 m USD whereas, full year product sales amounted to $23,641 m USD in 2015.

Total oncology product sales increased from $ 2,825 m USD in 2015 to $3,383 m USD in 2016. Total oncology product sales were $930 m USD for the forth quarter of 2016 while total oncology product sales were $716 m USD in the forth quarter of 2015.

Regional sales for 2016 equated to; US – $7,365 m USD, Europe -$5,064 m USD, Established ROW- $3,096 m USD and Emerging markets – $5,794 m USD. Total regional sales of oncology products were; US- $893 m USD, Europe – $733 m USD, Established ROW – $814 m USD and $943 m USD in Emerging Markets.

For AstraZeneca’s detailed sales figures, visit: View Source

On February 2, 2017 Bristol-Myers Squibb reported the U.S. Food and Drug Administration (FDA) has approved Opdivo injection, for intravenous use for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy (Press release, Bristol-Myers Squibb, FEB 2, 2017, View Source [SID1234517624]).

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This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1 The recommended dose for mUC is 240 mg administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity. In the CheckMate -275 trial, 19.6% (95% CI: 15.1-24.9; 53/270) of patients responded to treatment with Opdivo. The percentage of patients with a complete response was 2.6% (7/270) and the percentage of patients with a partial response was 17% (46/270). Among responders, the median duration of response was 10.3 months (range: 1.9+-12.0+ months). The median time to response was 1.9 months (range: 1.6-7.2).1

Opdivo is associated with the following Warnings and Precautions including immune-mediated: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reactions, encephalitis, other adverse reactions; infusion reactions; and embryo-fetal toxicity.1 Please see the Important Safety Information section below.

"Our goal to help more patients is further realized in today’s approval for Opdivo in this population and we are excited that our Immuno-Oncology therapy is now an option and potential hope for these patients," said Chris Boerner, president of U.S. Commercial, Bristol-Myers Squibb. "This is evidence of our commitment to Immuno-Oncology and to bringing therapies, like Opdivo, to more and more patients in need of additional choices."

The FDA granted the application priority review and previously granted Breakthrough Therapy Designation to Opdivo for the treatment of patients with locally advanced or mUC who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1

"Most people don’t know how common bladder cancer is and that it is the fifth most diagnosed cancer. That’s why we are dedicated to raising awareness and supporting research efforts that may offer more treatment options to patients who need them," said Stephanie Chisolm, director of Education and Research at Bladder Cancer Advocacy Network. "This approval is another exciting step forward for the bladder cancer community and provides needed hope to patients and their families."

Approval Based on Notable Objective Response Rate

CheckMate -275 is a Phase 2, open-label, single-arm, multicenter study evaluating Opdivo in patients with locally advanced or mUC who have disease progression during or following treatment with a platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.2 In this study, 270 patients received Opdivo 3 mg/kg administered intravenously every two weeks until disease progression or unacceptable toxicity. The recommended dose is 240 mg administered as an intravenous infusion over 60 minutes every two weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate (ORR) as defined by an independent radiographic review committee (IRRC). The median age of patients participating in the study was 66 years (range: 38-90), and 29% of patients had received ≥2 prior systemic regimens in the metastatic setting prior to enrolling in the study. Patients were included in the trial regardless of their PD-L1 status.1

In the trial, efficacy was evaluated in 270 patients with 6 months follow-up by confirmed ORR as determined by an IRRC, Opdivo demonstrated an ORR of 19.6% (95% CI: 15.1-24.9).1 Additional efficacy breakdown by PD-L1 expression were as follows:

Outcome, % (n)

All Patients
(n=270)


PD-L1 <1%
(n=146)
PD-L1 ≥1%
(n=124)

Confirmed ORR by IRRC
(95% CI)
19.6% (53)
(15.1-24.9) 15.1% (22)
(9.7-21.9) 25.0% (31)
(17.7-33.6)
Complete Response Rate 2.6% (7) 0.7% (1) 4.8% (6)
Partial Response Rate 17.0% (46) 14.4% (21) 20.2% (25)


"As an oncologist, a nearly twenty-percent response rate in advanced and metastatic bladder cancer is extremely encouraging and clinically meaningful in this patient population," said Dr. Jonathan E. Rosenberg, MD, Memorial Sloan Kettering Cancer Center.

Selected Safety Profile

The safety of Opdivo has been studied in 270 patients in the CheckMate -275 study. Patients were treated with Opdivo for a median of 3.3 months (range: 0-13.4+). In this study, serious adverse events occurred in 54% of patients. The most frequent serious adverse events reported in at least 2% of patients were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. The most common adverse reactions (≥20%) were fatigue (46%), musculokeletal pain (30%), nausea (22%), and decreased appetite (22%). Opdivo was discontinued due to adverse reactions in 17% of patients, and 46% of patients had a dose delay for an adverse reaction. Treatment-related death occurred in four patients due to pneumonitis or cardiovascular failure.1

About Bladder Cancer

Bladder cancer, which typically begins in the cells that line the inside of the bladder, is the fifth most commonly diagnosed cancer in the United States, with an estimated 77,000 new diagnoses in 2016 and over 16,000 deaths.3 Urothelial carcinoma is the most common type of bladder cancer, accounting for approximately 90% of diagnoses.4 The majority of bladder cancers are diagnosed at an early stage, but rates of recurrence and progression are high and approximately 50-70% of patients will experience a recurrence within five years.4 The poor durability of responses in the first-line setting presents a major challenge in the treatment of metastatic disease and there are limited treatment options in the second-line setting for advanced urothelial carcinoma.5