Infantile fibrosarcoma (IFS) is a rare pediatric cancer typically presenting in the first 2 years of life. Surgical resection is usually curative and chemotherapy is active against gross residual disease. However, when recurrences occur, therapeutic options are limited. We report a case of refractory IFS with constitutive activation of the tropomyosin-related kinase (TRK) signaling pathway from an ETS variant gene 6-neurotrophin 3 receptor gene (ETV6-NTRK3) gene fusion. The patient enrolled in a pediatric Phase 1 trial of LOXO-101, an experimental, highly selective inhibitor of TRK. The patient experienced a rapid, radiographic response, demonstrating the potential for LOXO-101 to provide benefit for IFS harboring NTRK gene fusions.
© 2016 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc.

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Follicular lymphoma (FL) is the second most common type of lymphoid cancer in Western Europe.
The aim of this study was to evaluate the cost utility of rituximab-bendamustine treatment compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) treatment as a first-line therapy for patients with advanced FL in Spain.
A Markov model was developed to estimate the cost effectiveness of rituximab-bendamustine compared with R-CHOP as first-line treatment for patients with advanced FL in the Spanish National Health System (NHS). Transitions between health states (progression-free, including induction and maintenance; first relapse; second relapse; and death) were allowed for the patient cohort in 4-week-long cycles. Clinical data for the extrapolation of progression-free survival curves were obtained from randomized trials. Mortality rates and utilities were obtained from the literature. Outcomes were measured as quality-adjusted life-years (QALYs). The total costs (€, 2013) included drug costs (ex-factory prices with mandatory deductions), disease management costs and adverse event-associated costs. Costs and outcomes were discounted at a 3 % annual rate. Probabilistic sensitivity analysis was performed using 10,000 Monte Carlo simulations to assess the model robustness.
Treatment and administration costs during the induction phase were higher for rituximab-bendamustine (€17,671) than for R-CHOP (€11,850). At the end of the 25-year period, the rituximab-bendamustine first-line strategy had a total cost of €68,357 compared with €69,528 for R-CHOP. Health benefits were higher for rituximab-bendamustine treatment (10.31 QALYs) than for R-CHOP treatment (9.82 QALYs). In the probabilistic analysis, rituximab-bendamustine was the dominant strategy over treatment with R-CHOP in 53.4 % of the simulations.
First-line therapy with rituximab-bendamustine in FL patients was the dominant strategy over treatment with R-CHOP; it showed cost savings and higher health benefits for the Spanish NHS.

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On April 20, 2016 Checkmate Pharmaceuticals , a clinical-stage biopharmaceutical company focused on developing novel approaches for cancer immunotherapy, reported the appointment of David Mauro, M.D., Ph.D . to the newly created position of Chief Medical Officer. Checkmate also announced the dosing of the first patient in a Phase 1b trial with CMP-001 in combination with pembrolizumab in melanoma patients who have either progressed on or failed to respond to at least 12 weeks of anti -‐ PD1 therapy. CMP -‐ 001 is a first -‐ in -‐ class CpG -‐ A oligonucleotide that activates the innate immune system via Toll -‐ like receptor 9 (TLR9) (Press release, Checkmate Pharmaceuticals, APR 20, 2016, View Source [SID1234516800]). The combination therapy has the potential to increase the proportion of cancer patients who respond to checkpoint inhibitor therapies and to increase the magnitude and duration of the anti -‐ tumor responses , providing added clinical benefit . Industry Veteran with Immun o -‐ Oncology Clinical Development and Leadership Expertise Dr. Mauro brings to Checkmate more than 15 years of experience in early and late stage oncology drug development, clinical and translational research , and medical affairs. Previously he served as Exe cu tive Vice President and Chief Medical Officer at Advaxis , where he was responsible for the strategy and oversight of the company’s clinical programs, including several combination drug programs with checkpoint inhibitor s . "We welcome David to the Checkmate team at this pivotal time ," said Art Krieg, M.D., Chief E xecutive Officer of Checkmate. " His deep knowledge and experience in immuno -‐ oncology , and specifically in the development of checkpoint inhibitor combinations, will be invaluable to Checkmate in the clinical development of CMP -‐ 001 for patients with advanced cancer ." Dr. Mauro has held senior level positions at Merck & Co. and Bristol Myers Squibb Company, where he was involved in the clinical development, trans la tional science , and life cycle management for multiple programs , including Keytruda ( pembrolizumab ), Erbitux (cetuximab), Sprycel (dasatinib), and Sylatron (peginterferon alfa -‐ 2b). He received his Bachelor of Science in Bioch emistry from Cornell University, his medical degree and his doctorate in pharmacology from Temple Univ ersity School of Medicine , and completed his residency training at the National Cancer Institute. A s Chief Medical Officer at Checkmate, Dr. Mauro will oversee the development of the Company’s current and future clinical programs, based on the TLR9 mechani sm of immune activation. " I am excited to be joining Checkmate as it progress es CMP -‐ 001 into the clinic in itially in melanoma patients ," said Dr. Mauro. "I look forward to working with the team to further expand the development of this compound in other indications and checkpoint inhibitor combinations . The immun o -‐ oncology field is evolving rapidly , and I believe that CMP -‐ 001 has the potential to increase the response rates to current checkpoint therapies a nd have a broad impact in the development of new standards of care f or oncology treatment." Initiation of Phase 1b Trial in Advanced Melanoma with a TLR9 Immune Activator Checkmate has dosed the first patient in its Phase 1b clinical study of CMP -‐ 001 . Th e trial is designed as a multi -‐ center, open -‐ label study of CMP -‐ 001 in combination with pembrolizumab for patients with advanced melanoma who have either progressed on an anti -‐ PD1 , or have failed to respond to at least 12 weeks of therapy . Patients will c ontinue on the approved dose and schedule of pembrolizumab, with the addition of intratumoral CMP -‐ 001 therapy. The trial will include a dose escalation study and will enroll patients in an expansion phase , as well as undertake correlative studies to characterize the immune effects of treatment in the blood and tumor. P atients will be monitored for safety and tolerability as well as possible clinical response . " We are excited to begin our clinical development of this new appr oac h of a ltering the tumor microenvironment with intratumoral CMP -‐ 001," said Dr. Krieg. " We believe this treatment should convert "cold" tumors , which lack immune activation and are not likely to respond to checkpoint inhibitors , in to immunologically "hot" tumors which are much more likely to respond to checkpoint inhibition . This has the potential to induce a powerful anti -‐ tumor CD8 + T cell immune response resulting in significantly increased response rates to checkpoint inhibitor therapy in multiple cancer indications ." About CMP -‐ 001 CMP -‐ 001 comprises a CpG -‐ A oligonucleotide packaged within a virus -‐ like particle . It is designed to activate the innate immune system via Toll -‐ like receptor 9 (TLR9) and mediate tumor control by the subsequent induction of both innate and adaptive anti -‐ tumor immune responses . CMP -‐ 001 is the only CpG -‐ A oligonucleotide in clinical development . It differs from the other major classes of TLR9 agonists in development , CpG -‐ B, and CpG -‐ C , by it s induction of much higher levels of type I interferons, without inducing immune suppressive IL -‐ 10. In addition, the virus -‐ like particle nature of CMP -‐ 001 will promote formation of immune complexes within tumors, providing an additional mechanism driving anti -‐ tumor i mmunity. In preclinical models , CMP -‐ 001 shows single agent activity in controlling growth of both local and distant tumors, with increased anti -‐ tumor ac tivity seen in combination with systemic anti -‐ PD -‐ 1 therapy. CMP -‐ 001 was licensed from Kuros Biosciences AG and was formerly known as CYT003. It has previously demonstrated a good safety profile and evidence of immune activity in over 700 patients who participated in clinical trials for non -‐ oncology indications.
About Checkmate
Checkmate Pharmaceuticals is a clinical stage company pursuing a novel approach to specifically activating the innate arm of the immune system to recognize and ultimately destroy tumor cells. The company is leveraging its expertise and the vast body of knowledge in the field of CpG oligonucleotides and is validating a n approach that will combine the ability of CpG DNA to activate an anti -‐ tumor T cell response with checkpoint inhibition to overcome a tumor’s ability to mute the immune response .
Checkmate’s founder and CEO, Dr. Art Krieg, discovered immune stimulatory CpG DNA in 1994 . S ince then , CpG containing DNA therapies have been administered to thousands of patients showing potent immune activation and a n acceptable safety profile. Checkmate is a privately held company headquartered in Cambridge, M A , whose Series A investors include Sofinnova Ventures and venBio

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Formation of new blood vessels in tumors, a process termed tumor angiogenesis, is a crucial step during oncogenic progression. Blocking tumor angiogenesis is therefore expected to have a profound impact on tumor growth. It took several decades of collective efforts to translate this intriguing idea into tangible clinical benefit. Today, anti-angiogenesis agents represent standard-of-care therapies for multiple types of cancers, and the clinical experience has taught us many lessons about the concept and application of anti-angiogenesis. This Perspective is an attempt to summarize these lessons and how they can be leveraged to improve anti-angiogenesis therapy.
Copyright © 2016 Elsevier Inc. All rights reserved.

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On April 20, 2016 Abbott (NYSE: ABT) reported financial results for the first quarter ended March 31, 2016 (Press release, Abbott, APR 20, 2016, View Source [SID:1234511137]).

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Abbott 2016 Q1 Performance at-a glance

Adjusted diluted EPS from continuing operations, which excludes specified items, was $0.41 in the first quarter, above Abbott’s previous guidance range. Reported diluted EPS from continuing operations under GAAP was $0.04 in the first quarter.
First-quarter worldwide sales of $4.9 billion increased 5.1 percent on an operational basis and decreased 0.2 percent on a reported basis.
Abbott is raising its full-year 2016 adjusted EPS guidance range for continuing operations to $2.14 to $2.24 from $2.10 to $2.20. Projected full-year 2016 EPS for continuing operations under GAAP is $1.36 to $1.46.
Abbott’s recent innovations and product launches contributed to sales growth in the first quarter. Select recently launched products include ElevaTM in the premium segment of the Chinese infant formula market; Abbott’s portfolio of infant and toddler non-GMO nutrition products in the U.S.; MitraClip, Abbott’s structural heart product for the treatment of mitral regurgitation; Freestyle Libre in Europe; Supera peripheral stent in the U.S. for treatment of blockages in the superficial femoral artery; and Abbott’s portfolio of TECNIS intraocular lenses for the treatment of cataracts.
In the first quarter, Abbott received European approval for use in children and teens of its revolutionary FreeStyle Libre Flash Glucose Monitoring System that eliminates routine finger sticks and finger-stick calibration. In Abbott Vascular, AbsorbTM, Abbott’s fully dissolving vascular stent, earned a positive review from an independent U.S. Food and Drug Administration advisory committee.
"We’re off to a good start to the year and are raising our full-year adjusted EPS guidance range," said Miles D. White, chairman and chief executive officer, Abbott. "All four of our businesses met or exceeded our growth expectations and underlying demand remains strong."

FIRST-QUARTER BUSINESS OVERVIEW

Following are sales by business segment and commentary for the first quarter:

Total Company
($ in millions)

% Change vs. 1Q15

Sales 1Q16

Int’l

Total

U.S.

Int’l

Total

U.S.

Operational

Reported

Operational

Reported
Total *

1,531

3,354

4,885

1.9

6.6

(1.2)

5.1

(0.2)
Nutrition

719

952

1,671

4.9

3.9

(3.2)

4.3

0.1
Diagnostics

339

779

1,118

3.7

8.2

1.8

6.9

2.3
Established Pharmaceuticals
—

888

888

n/a

11.0

(1.0)

11.0

(1.0)
Medical Devices

466

731

1,197

(3.9)

3.5

(1.3)

0.5

(2.4)

Note: Operational growth reflects percentage change over the prior year excluding the impact of exchange rates.
* Total Abbott Sales from continuing operations include Other Sales of $11 million.
n/a = Not Applicable.

First-quarter 2016 worldwide sales of $4.9 billion increased 5.1 percent on an operational basis and decreased 0.2 percent on a reported basis, including an unfavorable 5.3 percent effect of foreign exchange.

U.S. sales increased 1.9 percent, led by 9.2 percent growth in Point of Care Diagnostics, 7.5 percent growth in Medical Optics, and 4.9 percent growth in Nutrition.

International sales increased 6.6 percent on an operational basis and decreased 1.2 percent on a reported basis in the first quarter. International operational sales growth was led by 11.0 percent growth in Established Pharmaceuticals, 11.0 percent growth in Diabetes Care and 8.2 percent growth in Diagnostics.

Nutrition
($ in millions)

% Change vs. 1Q15

Sales 1Q16

Int’l

Total

U.S.

Int’l

Total

U.S.

Operational

Reported

Operational

Reported
Total

719

952

1,671

4.9

3.9

(3.2)

4.3

0.1
Pediatric

403

564

967

4.7

4.1

(2.3)

4.4

0.5
Adult

316

388

704

5.2

3.6

(4.6)

4.3

(0.5)

Worldwide Nutrition sales increased 4.3 percent in the first quarter on an operational basis and 0.1 percent on a reported basis, including an unfavorable 4.2 percent effect of foreign exchange.

Worldwide Pediatric Nutrition sales increased 4.4 percent on an operational basis and 0.5 percent on a reported basis in the quarter, including an unfavorable 3.9 percent effect of foreign exchange. In the U.S., above-market sales growth was led by recently launched infant and toddler non-GMO products, including Similac Advance Non-GMO and Go & Grow by Similac Non-GMO. International growth was led by market share expansion of Eleva in the premium segment of the Chinese infant formula market, as well as continued strong performance in Russia and across several countries in Latin America.

Worldwide Adult Nutrition sales increased 4.3 percent on an operational basis and decreased 0.5 percent on a reported basis in the quarter, including an unfavorable 4.8 percent effect of foreign exchange. International Adult Nutrition growth was led by continued strong growth of Ensure and Glucerna in Latin America and other priority geographies. U.S. Adult Nutrition sales growth of 5.2 percent was led by growth of Ensure in the retail and institutional market segments. During the quarter, Abbott launched Ensure Enlive, a nutrition drink that helps adults rebuild lost muscle and regain strength and energy.

Diagnostics
($ in millions)

% Change vs. 1Q15

Sales 1Q16

Int’l

Total

U.S.

Int’l

Total

U.S.

Operational

Reported

Operational

Reported
Total

339

779

1,118

3.7

8.2

1.8

6.9

2.3

Core Laboratory

190

695

885

2.4

8.6

2.1

7.3

2.1

Molecular

47

61

108

(2.1)

3.2

(3.4)

1.0

(2.8)

Point of Care

102

23

125

9.2

9.6

7.2

9.3

8.8

Worldwide Diagnostics sales increased 6.9 percent in the first quarter on an operational basis, driven by continued above-market growth globally, including strong growth in both emerging and developed markets. Sales increased 2.3 percent on a reported basis, including an unfavorable 4.6 percent effect of foreign exchange.

Core Laboratory Diagnostics sales increased 7.3 percent in the quarter on an operational basis and 2.1 percent on a reported basis, including an unfavorable 5.2 percent effect of foreign exchange. Operational sales growth in the quarter was driven by double-digit growth in emerging markets.

Molecular Diagnostics sales increased 1.0 percent in the quarter on an operational basis and decreased 2.8 percent on a reported basis, including an unfavorable 3.8 percent effect of foreign exchange. Strong operational sales growth in Abbott’s infectious disease testing business was offset, as expected, by the planned scale down of its genetics business.

Point of Care Diagnostics sales increased 9.3 percent in the quarter on an operational basis and 8.8 percent on a reported basis, including an unfavorable 0.5 percent effect of foreign exchange. Sales growth was led by continued adoption of Abbott’s i-STAT handheld system in the U.S. and international markets.

Established Pharmaceuticals
($ in millions)

% Change vs. 1Q15

Sales 1Q16

Int’l

Total

U.S.

Int’l

Total

U.S.

Operational

Reported

Operational

Reported
Total

—

888

888

n/a

11.0

(1.0)

11.0

(1.0)
Key Emerging Markets

—

634

634

n/a

11.9

(3.2)

11.9

(3.2)
Other

—

254

254

n/a

8.6

4.9

8.6

4.9

Established Pharmaceuticals sales increased 11.0 percent in the first quarter on an operational basis and decreased 1.0 percent on a reported basis, including an unfavorable 12.0 percent effect of foreign exchange.

Key Emerging Markets include India, Russia, Brazil and China, along with several additional emerging markets that represent the most attractive long-term growth opportunities for Abbott’s branded generics product portfolio. Sales in these key geographies increased 11.9 percent on an operational basis and decreased 3.2 percent on a reported basis, including an unfavorable 15.1 percent effect of foreign exchange.

Operational sales growth in Key Emerging Markets was led by continued double-digit growth in India, which comprises more than 20 percent of Abbott’s Established Pharmaceuticals sales. Sales growth in India was led by double-digit growth across several core therapeutic areas, including women’s health, gastroenterology, and cardio-metabolics. During the quarter, Abbott also achieved above-market growth in China and several countries in Latin America as it continues to expand its presence and portfolio in these key geographies.

Medical Devices
($ in millions)

% Change vs. 1Q15

Sales 1Q16

Int’l

Total

U.S.

Int’l

Total

U.S.

Operational

Reported

Operational

Reported

Total

466

731

1,197

(3.9)

3.5

(1.3)

0.5

(2.4)

Vascular

289

396

685

1.9

0.2

(4.5)

0.9

(1.9)

Diabetes Care

69

174

243

(31.6)

11.0

4.8

(5.2)

(9.1)

Medical Optics

108

161

269

7.5

4.2

0.5

5.4

3.2

Vascular Product Lines:

Coronary Devicesa)

194

336

530

4.9

(1.1)

(5.6)

0.9

(2.0)

Endovascularb)

73

60

133

9.5

8.6

2.9

9.0

6.4

a) Includes DES / BVS product portfolio, structural heart, guidewires, balloon catheters, and other coronary products.
b) Includes vessel closure, carotid stents and other peripheral products.

Worldwide Medical Devices sales increased 0.5 percent in the first quarter on an operational basis and decreased 2.4 percent on a reported basis, including an unfavorable 2.9 percent effect of foreign exchange.

Worldwide sales of Vascular products increased 0.9 percent in the quarter on an operational basis and decreased 1.9 percent on a reported basis, including an unfavorable 2.8 percent effect of foreign exchange. Sales of MitraClip, Abbott’s device for the treatment of mitral regurgitation, increased double-digits globally, as Abbott continues to build the market for this first-in-class device. Growth in Abbott’s Endovascular business was driven by vessel closure products and Supera, Abbott’s peripheral stent for the treatment of blockages in the superficial femoral artery and proximal popliteal artery in the upper leg. In March, Absorb, Abbott’s fully dissolving vascular stent, received a positive review from an independent U.S. FDA advisory committee.

Worldwide Diabetes Care sales decreased 5.2 percent in the quarter on an operational basis and 9.1 percent on a reported basis, including an unfavorable 3.9 percent effect of foreign exchange. Strong international sales growth was driven by continued consumer uptake of FreeStyle Libre, Abbott’s revolutionary Flash Glucose Monitoring System that eliminates routine finger sticks and finger-stick calibration. During the quarter, Abbott received European approval for use of FreeStyle Libre in children and teens. In the U.S., sales were impacted by competitive and market dynamics.

Worldwide Medical Optics sales increased 5.4 percent in the quarter on an operational basis and 3.2 percent on a reported basis, including an unfavorable 2.2 percent effect of foreign exchange. Operational sales growth was driven by continued market uptake of cataract products in the premium intraocular lens segment, including TECNIS Symfony and TECNIS Toric lenses.

ABBOTT RAISES FULL-YEAR ADJUSTED EARNINGS-PER-SHARE GUIDANCE RANGE

Abbott is raising its full-year 2016 guidance range for earnings per share from continuing operations, excluding specified items, to $2.14 to $2.24 from $2.10 to $2.20.

Abbott forecasts net specified items for the full year 2016 of approximately $0.78 per share. Specified items include intangible amortization expense, the impact of the Venezuelan currency devaluation, and charges associated with cost reduction initiatives and deal and other expenses, partially offset by the favorable resolution of various tax positions from prior years.

Including net specified items, projected earnings per share from continuing operations under Generally Accepted Accounting Principles (GAAP) would be $1.36 to $1.46 for the full year 2016.

ABBOTT DECLARES 369TH QUARTERLY DIVIDEND

On Feb. 19, 2016, the board of directors of Abbott declared the company’s quarterly dividend of $0.26 per share. Abbott’s cash dividend is payable May 16, 2016, to shareholders of record at the close of business on April 15, 2016. This marks the 369th consecutive quarterly dividend paid by Abbott.

Abbott is a member of the S&P 500 Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for 25 consecutive years.