PharmaCyte Biotech Moves Closer to Filing IND with Naming of Comparator Arm for Upcoming Clinical Trial and Discusses Pivotal Trial Opportunity

On February 13, 2017 PharmaCyte Biotech, Inc. (OTCQB:PMCB), a clinical stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported the comparator arm for its upcoming clinical trial and provided additional clarification on its recent pre-IND meeting with the U.S. Food and Drug Administration (FDA) regarding its upcoming clinical trial in locally advanced, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, FEB 13, 2017, View Source [SID1234517708]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the company’s upcoming trial, the comparator arm that PharmaCyte’s pancreatic cancer therapy will be compared to is the combination of the cancer drug 5-fluorouracil (FU) and the compound leucovorin (LV). The necessary and quick decision was made by Dr. Manuel Hidalgo, the Principal Investigator for the upcoming clinical, Dr. Daniel Von Hoff with Translational Drug Development (TD2), the CRO for PharmaCyte’s clinical trial, and Dr. Matthias Löhr, the Chairman of PharmaCyte’s Medical and Scientific Advisory Board.

"After our pre-IND meeting I am more confident and enthusiastic than ever about PharmaCyte’s ability to validate its therapy for locally advanced, inoperable pancreatic cancer in a human clinical trial," stated PharmaCyte’s Chief Executive Officer, Kenneth L Waggoner.

He continued, "And I am quite gratified that the FDA sees enough potential in our product to consider our trial a pivotal one under the right circumstances. Now the mission for our entire team is to work diligently towards the submission of our IND to the FDA. We all feel that the suggested changes we received from the FDA should not take long to make and will certainly be well worth it in the long run. For example, we quickly gained agreement on the comparator arm for the trial and, in doing so, we’ve moved closer to filing our IND with the FDA."

PharmaCyte’s management, Dr. Manuel Hidalgo, TD2 and TD2’s consulting statistician are actively working to finalize the number of patients that will be included in the trial. This is the final element and will complete the adjustments necessary for a newly designed trial.

In PharmaCyte’s recent pre-IND meeting with the FDA, the FDA stated that it would be willing to change PharmaCyte’s clinical trial from an "exploratory" trial to a "pivotal" trial under certain conditions. A pivotal trial is a clinical trial intended to provide evidence for a drug marketing approval by the FDA.

This indeed is a landmark moment in PharmaCyte’s history. Generally, a pivotal trial must be a Phase 3 trial (which PharmaCyte’s upcoming trial could be labeled); in such a trial several hundred patients can be treated. However, the FDA indicated that: (i) if PharmaCyte’s therapy shows real promise; (ii) includes a sufficient number of patients; and (iii) includes primary endpoints of overall survival (OS) and safety rather than progression free survival (PFS) and safety, the trial may be considered a pivotal trial.

Mr. Waggoner said of this opportunity, "This is good news for PharmaCyte shareholders since the change from an "exploratory" trial to a "pivotal" trial can eliminate one or two lengthy and costly trials and potentially make PharmaCyte’s Cell-in-a-Box-based product, CypCaps, "market-ready" in a much shorter period of time than anticipated. It may also accelerate the overall development timeline if the results are very positive, thus making the therapy more attractive to potential investors or suitors."

To be a pivotal trial, the FDA wants at least 100 patients treated with CypCaps for purposes of determining the safety of PharmaCyte’s therapy. In the trial’s original design only 40 or so patients would have received CypCaps and been evaluated for safety.

Other highly positive news provided by Mr. Waggoner concerning the pre-IND meeting with the FDA included:

agreement with the FDA that PharmaCyte is on the "right track" in its development program;
agreement with the FDA on the cell line that will be used in the clinical trial;
agreement with the FDA on the patient population to be studied in the clinical trial;
agreement with the FDA on the secondary endpoints of the clinical trial, except that PFS will be added to the list of secondary endpoints if the trial becomes a pivotal trial;
agreement with the FDA on the number of patients needed to comprise an adequate safety database for a Biologics Licensing Application for CypCaps;
agreement that the FDA believes CypCaps is a drug/device combination product;
agreement with the FDA that it will assist PharmaCyte in its development program; and
agreement with the FDA that the next step for PharmaCyte is to submit an IND.
There is still a "hard stop" at the six-month mark after a certain number of patients have been enrolled in the trial to review the data generated to that point. The timing of this hard stop may change, however, to the point in time when 50% of the patients have been treated. Because the clinical trial is an "open-label" trial (the trial is not a "blinded" study), this interim analysis should give PharmaCyte an important indication of the successfulness of its CypCaps therapy for LAPC.

Mr. Waggoner commented on the significance of following the FDA’s guidance moving forward stating, "We have one shot at this, and we intend to get it right. We greatly appreciate the continued patience and support of our shareholders during this process."

Actelion announces excellent financial results for 2016

On February 14, 2017 Actelion Ltd (SIX: ATLN) reported its results for the full year 2016 (Press release, Actelion, FEB 13, 2017, View Source [SID1234517712]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

FINANCIAL HIGHLIGHTS

Sales growing to CHF 2,412 million (+15% at CER)
Opsumit sales continue strong trajectory and grow to CHF 831 million (+57% at CER)
Uptravi sales reach CHF 245 million in first year of launch – driven by the US
US GAAP operating income grows to CHF 789 million (+14% at CER)
Core operating income grows to CHF 992 million (+17% at CER)
USD 30 billion proposal by Johnson & Johnson to acquire Actelion

PROPOSED TRANSACTION HIGHLIGHTS

Actelion to be acquired by Johnson & Johnson for $ 30 billion with spin-out of new R&D company, listed on Swiss stock exchange
Actelion shareholders to receive 280 US dollars per Actelion share in all-cash tender offer and one share of new R&D company for each Actelion share as stock dividend
Johnson & Johnson to acquire Actelion’s marketed products in particular its leading PAH franchise
Johnson & Johnson to also acquire global rights to Actelion’s promising advanced late-stage therapies, ponesimod and cadazolid
New R&D company launching with cash of CHF 1 billion to continue the culture of innovation with early stage R&D pipeline
Johnson & Johnson will also receive an option on an endothelin receptor antagonist (ACT-132577) currently being developed for resistant hypertension

FINANCIAL OVERVIEW

% variance
in CHF million
(except for per share data) FY 2016 FY 2015 in CHF at CER(1)
US GAAP results
Net revenue 2,418 2,045 18 15
Operating income 789 656 20 14
Net income 696 552 26 19
Diluted EPS 6.46 4.91 32 25
Core performance(2)
Product sales 2,412 2,042 18 15
Core operating income 992 814 22 17
Core net income 881 693 27 22
Core diluted EPS 8.18 6.16 33 27
Cash flow FY 2016 FY 2015
Operating cash flow 920 658
Capital expenditure (57) (44)
Free cash flow 90 (800)
Net cash position as of 31 December 495 405
CER percentage changes are calculated by reconsolidating both the 2015 and 2016 results at constant currencies (the average monthly exchange rates for 2015).
Actelion continues to measure and report core operating performance, which management believes more accurately reflects the underlying business performance. The Group believes that these non-GAAP financial measurements provide useful supplementary information to investors. These non-GAAP measures are reported in addition to, not as a substitute for, US GAAP financial performance.

Jean-Paul Clozel, MD, Chief Executive Officer, commented: "With Johnson & Johnson’s proposed acquisition of Actelion and the spin-out of a new R&D company, we have created unprecedented value for all of our stakeholders. Our current PAH portfolio and our late-stage pipeline will have expanded potential as part of Johnson & Johnson. With the creation of a new R&D company we also have the opportunity to realize the value potential we have created with our discovery engine and early-stage pipeline. I am very proud of what we’ve achieved, and I am very excited about the challenges and opportunities ahead."

Otto Schwarz, Chief Operating Officer, commented: "The significant clinical utility of Opsumit resulted in continued strong patient uptake with more than 21,000 patients currently receiving therapy. Moreover, after just one year on the US market, we can say that the Uptravi launch has been very successful by any standards, proving the high unmet medical need for oral prostacyclin therapy and validating our commercial strategy. I strongly believe that, as a part of the Johnson & Johnson family of companies, we will be able to serve even more patients by opening new markets and creating additional opportunities for our products."

André C. Muller, Chief Financial Officer, commented: "Actelion’s 2016 performance has been impressive with the company delivering record sales and earnings. The proposed transaction with Johnson & Johnson announced on 26 January will enable Actelion shareholders to not only monetize their holdings at 280 US dollars per share but also retain future upside potential with the distribution of 1 share in the newly created R&D company for every Actelion share. Both companies are now working to finalize the operational and financial details of the split and prepare the listing of the new company."

SALES UPDATE
Actelion’s excellent commercial performance during 2016 was driven by the outstanding Uptravi launch in the US and Opsumit’s sustained strong growth trajectory. During the fourth quarter of 2016, combined sales of the company’s outcome-based PAH portfolio – Opsumit, Uptravi and Veletri – reached 55% of total sales, demonstrating the significant progress made in the fundamental transformation of the PAH business.

In the US, sales increased by 25% at CER, driven by the strong Uptravi launch, the continued Opsumit momentum due to share gains in an expanding ERA market. European sales were 1% higher compared to 2015. A strong Opsumit performance and solid Tracleer use in the digital ulcer indication were impacted by continued pricing pressure and market erosion from bosentan generics, particularly in Spain. Sales in Japan increased by 19% at CER, driven by very strong sales of Opsumit (launched in June 2015), Tracleer momentum in the digital ulcer indication and Zavesca (Japanese trade name Brazaves).

Comparing average exchange rates for 2016 to 2015, the Swiss franc weakened, mostly against the US dollar, euro and Japanese yen, resulting in a positive currency variance of 63 million Swiss francs.

Sales by product – FY2016

% variance
in CHF millions FY 2016 FY 2015 in CHF at CER
Opsumit 831 516 61 57
Tracleer 1,020 1,212 -16 -18
Uptravi 245 - nm nm
Veletri 97 83 17 12
Ventavis 73 105 -30 -32
Valchlor 35 27 30 27
Zavesca 104 92 13 12
Others 8 7 7 8
Total product sales 2,412 2,042 18 15
*nm = not meaningful

Sales by product – Q4 2016

% variance
in CHF millions Q4 2016 Q4 2015 in CHF at CER
Opsumit 235 162 45 43
Tracleer 229 278 -17 -19
Uptravi 85 - nm nm
Veletri 26 23 12 9
Ventavis 15 24 -37 -38
Valchlor 10 8 20 19
Zavesca 26 24 10 10
Others 2 2 -6 -7
Total product sales 627 519 21 19
Sales by region – FY 2016

% variance
in CHF millions FY 2016 FY 2015 in CHF at CER
United States 1,306 1,026 27 25
Europe* 646 634 2 1
Japan 258 190 36 19
Rest of the world 201 192 5 6
Total product sales 2,412 2,042 18 15
*Europe = EU28 and Switzerland

Sales by region – Q4 2016

% variance
in CHF millions Q4 2016 Q4 2015 in CHF at CER
United States 342 259 32 30
Europe* 162 159 2 4
Japan 77 58 31 17
Rest of the world 47 42 10 9
Total product sales 627 519 21 19
*Europe = EU28 and Switzerland

PAH FRANCHISE
Opsumit
Sales of Opsumit (macitentan) amounted to 831 million Swiss francs for 2016, an increase of 57% at CER compared to 2015. The strong growth across all regions and all relevant markets (Opsumit is now available in almost 40 markets) was driven by solid quarterly increases in the number of patients treated in an expanding ERA market due to increased use in combination with PDE-5 inhibitors, and some upgrades from Tracleer, notably in Japan.

Uptravi
Sales of Uptravi (selexipag) amounted to 245 million Swiss francs for 2016. Since the US launch at the beginning of January 2016, patient demand has continued to increase with sales of 232 million Swiss francs (which includes 30 million Swiss francs for the build-up of inventory in the US). For the fourth quarter, US sales amounted to 77 million Swiss francs, compared to 66 million Swiss francs in the third quarter, 45 million Swiss francs in the second quarter and 15 million Swiss francs in the first quarter of 2016. In other geographies, Uptravi sales were driven by the particularly successful launch in Germany. Uptravi is also available in several other markets; it was most recently launched with full reimbursement in the Netherlands and Switzerland.

At the end of 2016, just over 2,400 patients were being treated with Uptravi globally, with more than 1,900 patients coming from the US.

Tracleer
Sales of Tracleer (bosentan) amounted to 1,020 million Swiss francs for 2016, a decrease of 18% at CER compared to 2015. This was driven to a large extent by volume erosion resulting from the significant impact of Opsumit uptake on the Tracleer patient base and by increased generic competition, notably in Spain, where generic bosentan entered the market in January 2016. Tracleer sales were supported by the digital ulcer indication in Europe and Japan.

Following the Pediatric Investigation Plan (PIP) compliance statement from the European Committee for Medicinal Products for Human Use (CHMP), applications for extension of the Supplementary Protection Certificate (SPC) were granted in all possible 19 EU countries until the end of August 2017.

Veletri
Sales of Veletri (epoprostenol for injection) amounted to 97 million Swiss francs for 2016, an increase of 12% at CER compared to 2015. This increase was mostly driven by France, Italy, Spain and the UK. Demand in Japan, where it is marketed as Epoprostenol ACT, remained strong, however sales growth was mitigated by a 12% price cut effective March 1, 2016. In February 2017, Actelion Pharmaceuticals Japan proudly announced that Epoprostenol ACT received a label extension for dosage and administration in pediatric patients with PAH.

Ventavis
Sales of Ventavis (iloprost) amounted to 73 million Swiss francs for 2016, a decrease of 32% at CER compared to 2015 due to competitive pressures, including the availability of Uptravi. Underlying units decreased by 37%.

SPECIALTY PRODUCTS
Valchlor
Sales of Valchlor (mechlorethamine) amounted to 35 million Swiss francs for 2016, an increase of 27% at CER compared to 2015. In the US, the company has made good progress in establishing Valchlor as a valuable option in the treatment algorithm for early-stage mycosis fungoides, a type of Cutaneous T-Cell Lymphoma (MF-CTCL).

In December 2016, the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), issued a positive opinion for the use of chlormethine gel 160 micrograms/g (Ledaga) for the treatment of mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in adult patients and recommended that the European Commission approves the product. The European Commission is expected to issue a final decision by the end of February 2017.

Zavesca
Sales of Zavesca (miglustat) amounted to 104 million Swiss francs for 2016, an increase of 12% at CER compared to 2015.

Sales in the US were strong, due to a relatively low prior year base as a consequence of an inventory adjustment. In Europe, sales were flat due to the launch of generic miglustat (for the type 1 Gaucher disease indication only), which mitigated the continued strong, double-digit growth in the Niemann-Pick type C (NP-C) indication. Globally, the number of patients receiving Zavesca grew by 6%, compared to 2015, which was driven by a 13% increase in the treatment of patients with NP-C.

CORE R&D EXPENDITURE
The excellent commercial performance enabled Actelion to advance both the late and earlier stage pipeline, resulting in increased R&D expenditure which translates into a ratio of R&D core operating expenses to sales of 21%, slightly higher than in 2015. Core R&D expenses amounted to 509 million Swiss francs, an increase of 25% at CER. This increase was driven by higher clinical trial expenses, mainly driven by the strong recruitment in the Phase III OPTIMUM study (ponesimod in multiple sclerosis; announced in April 2015) and the Phase III IMPACT study (Cadazolid in Clostridium difficile associated diarrhea), as well as costs related to the preparation and initiation of Phase II studies for Actelion’s new ERA in specialty cardiovascular disorders and DORA in insomnia.

CORE OPERATING INCOME
Core operating income amounted to 992 million Swiss francs, an increase of 17% at CER.

CORE EPS
Diluted core earnings per share were CHF 8.18 for the full year 2016, an increase of 27% at CER compared to the same period of 2015.

DELIVERING VALUE TO SHAREHOLDERS
In-keeping with its commitment to maximizing shareholder value, Actelion returned 428 million Swiss francs to shareholders through the second-line share buyback as well as the increased dividend of CHF 1.50 per share, paid in May 2016. Actelion’s shares performed strongly throughout 2016 regardless of the extraordinary volatility created by the strategic discussions initiated in late November. The unaffected share price performance up until the strategic discussions became public was an increase of approximately 15%. At the end of the year, Actelion’s stock traded at 220.5 Swiss francs per share, an increase of 58% for the calendar year. The resulting total shareholder return (TSR) for 2016 amounted to 59%.

On 26 January 2017, Actelion and Johnson & Johnson jointly announced that they have entered into a definitive transaction agreement under which Johnson & Johnson will launch an all-cash tender offer in Switzerland to acquire all of the outstanding shares of Actelion for 280 US dollars per share. Additionally, Actelion shareholders will receive one share of a newly created R&D company that will be spun out concurrently with the closing of the proposed transaction.

CLINICAL DEVELOPMENT PIPELINE
The pipeline continued to strengthen with substantial progress made with several compounds:

The ongoing Phase III program IMPACT investigating cadazolid treatment in patients suffering from Clostridium difficile-associated diarrhea is progressing well; results are expected in the first half of 2017.
In the third quarter of 2016, Actelion announced the initiation of the Phase III POINT study, which investigates the use of combination therapy with ponesimod, an orally active, selective sphingosine-1-phosphate receptor 1 (S1P1) immunomodulator, and dimethyl fumarate (Tecfidera) for patients with relapsing multiple sclerosis (RMS). The POINT study – which will be conducted under a Special Protocol Assessment (SPA) agreement with the FDA – is the first to assess the concurrent administration of two oral therapies in MS with the objective to improve disease control in this progressive, debilitating neurological disorder. Ponesimod is also being studied in the Phase III OPTIMUM study to compare the efficacy and safety of ponesimod with teriflunomide (Aubagio) in patients with RMS. The study is making good progress, with enrollment expected to be complete in Q1 2017.
Also in the third quarter of 2016, the company advanced its new dual orexin receptor antagonist (DORA) into Phase II development in patients with insomnia. The Phase II program consists of two studies, one in adult and one in elderly patients, and is designed to evaluate the effect of Actelion’s DORA versus placebo on sleep maintenance and sleep initiation, as well as next-day residual effect and next-day performance. The study in adults also includes a zolpidem reference arm. The decision to move into a Phase II program was based on excellent data collected from the preclinical and Phase I clinical program, as well as a thorough understanding of the potential of dual orexin receptor antagonism on sleep efficacy and architecture.
With macitentan (Opsumit), the company is conducting a pediatric study, TOMORROW, to evaluate the effect of macitentan on delaying disease progression in children with PAH using a pediatric formulation of macitentan. Recruitment is expected to start in Q1 2017.
Actelion will assess the efficacy and safety of macitentan in stable Fontan-palliated adolescents and adults in the Phase III study RUBATO. The primary objective of this study is to assess the effect of macitentan as compared to placebo on exercise capacity through cardiopulmonary exercise testing (peak VO2). The duration of the study is expected to be approximately 28 months; the start is planned for mid-2017.
A Phase II study with macitentan, MERIT, assessed the efficacy, safety and tolerability of macitentan in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). The study was completed in September 2016 and delivered very positive results, meeting its primary endpoint of a significant reduction in pulmonary vascular resistance (PVR) with macitentan compared with placebo, and also showing a significant positive effect on exercise capacity for macitentan over placebo.
A Phase III study with macitentan, MAESTRO, assessed the effects of macitentan on exercise capacity in patients with Eisenmenger Syndrome. The study was completed in January 2017, but did not meet the primary endpoint of significantly improving exercise capacity with macitentan compared with placebo.
Lucerastat is being evaluated for the treatment of Fabry disease. In an initial Phase Ib study, patients receiving enzyme replacement therapy who were treated with lucerastat demonstrated a marked decrease in the accumulation of metabolic substrates thought to be responsible for the lesions characteristic of this disease. Actelion is currently in discussions with health authorities to move directly to Phase III.
Compound Indication Study Status
Phase III Cadazolid1 Clostridium difficile-associated diarrhea IMPACT Ongoing
Macitentan1 Pediatric PAH TOMORROW Initiating
Macitentan1 Portopulmonary hypertension (PoPH) PORTICO Ongoing
Macitentan1 Fontan-palliated patients RUBATO Initiating


Ponesimod1

Multiple sclerosis OPTIMUM Ongoing
Ponesimod1 Multiple sclerosis POINT Ongoing
Phase II Cenerimod2 Systemic lupus erythematosus - Ongoing
Clazosentan2 Reversal of vasospasm associated with aneurysmal subarachnoid hemorrhage REVERSE Ongoing
Dual Orexin Receptor Antagonist2 Insomnia - Ongoing
Endothelin Receptor Antagonist
(ACT-132577)2 Specialty cardiovascular disorders - Ongoing
Macitentan1 Chronic thromboembolic pulmonary hypertension MERIT Complete
Phase Ib Lucerastat2 Fabry disease - Complete
Phase I New Chemical Entity2 Cardiovascular disorders - Ongoing
New Chemical Entity2 Inflammatory disorders - Ongoing
Selective Orexin 1 Receptor Antagonist2 Neurological disorders - Ongoing
T-type Calcium Channel Blocker2 Neurological disorders - Ongoing
1 Upon completion of the proposed transaction these assets would be developed by Johnson & Johnson
2 Upon completion of the proposed transaction these assets would be developed by the new R&D company

HUMAN RESOURCES
At the end of 2016, Actelion employed 2,624 permanent employees worldwide, an increase of 3% (or 77 permanent positions) compared to the end of 2015.

ANNUAL REPORT
Full details on the progress made in 2016 are available in Actelion’s 2016 Annual Report, at www.actelion.com/annual-report.

NOTES TO SHAREHOLDERS:
The next General Meeting of Shareholders will take place on or around 05 April, 2017, the date will be confirmed with the publication of the offer prospectus by Johnson & Johnson on or around 16 February 2017.

In light of the expected completion of the proposed transaction with Johnson & Johnson, the Board of Directors will propose to carry forward the 2016 accumulated profit and therefore not distribute any cash dividend.

RESULTS DAY CENTER
Investor community: To make your job easier, we provide links to all relevant documentation, such as a full financial review, reconciliation US-GAAP to Core results and geographical breakdown by product, from the Results Day Center on our corporate website: www.actelion.com/results-day-center.

Transgene and Léon Bérard Cancer Center Announce Dosing of the First Patient in a Phase 1 Immunotherapy Clinical Trial Evaluating the Intra-Tumoral Co-Administration of Pexa-Vec plus Ipilimumab (Yervoy®) in Solid Cancers

On February 13, 2017 Transgene (Paris:TNG), a company focused on designing and developing viral-based immune-targeted therapies for the treatment of cancers and infectious diseases, reported that the 1st patient in the ISI-JX trial has been treated at the Léon Bérard Cancer Center in Lyon, France (Press release, Transgene, FEB 13, 2017, View Source [SID1234517711]). ISI-JX is a Phase 1 clinical trial evaluating the intra-tumoral co-administration of Pexa-Vec in combination with ipilimumab in solid tumors (NCT02977156). This investigator initiated trial promoted by the Leon Bérard Cancer Center will enroll patients with metastatic and/or locally advanced solid tumors.
Pexa-Vec is a GM-CSF expressing vaccinia derived oncolytic virus co-developed by Transgene and SillaJen. Ipilimumab is a monoclonal antibody targeted against the immune checkpoint CTLA-4 and is currently approved for the treatment of melanoma (Yervoy, Bristol-Myers Squibb).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The open-label trial that will recruit up to 60 patients in several clinical centers in France. First readouts could be expected towards the end of 2017. The trial will evaluate the safety of the combination and evaluate the first signals for efficacy.

Dr Aurélien Marabelle MD, PhD, from Gustave Roussy, a world expert in immunotherapy clinical research and coordinating investigator of the study commented: "We believe in the synergistic potential of the combination between oncolytic viruses and immune checkpoint-targeted antibodies. Also, we believe that the intra-tumoral co-delivery of these immunotherapies will trigger a better priming of the anti-tumor immune response while avoiding off-target toxicities. We hope this novel "in situ immunization" strategy will overcome the resistance to cancer immunotherapy that we observe in many patients."

The combination of Pexa-Vec and ipilimumab aims at targeting two distinct steps in the immune response against cancer cells and is expected to be significantly more effective than either product alone. Pexa-Vec is an oncolytic virus designed to (i) selectively destroy cancer cells through the direct lysis (breakdown) of cancer cells via viral replication, (ii) reduce the blood supply to tumors through vascular disruption, and (iii) stimulate the body’s immune response against cancer cells. Its mechanism of action and its safety profile make it an appropriate candidate for combinations with immune checkpoint inhibitors (ICIs) such as ipilimumab, which acts as a brake on the body’s immune response to cancer cells thereby potentially improving Pexa-Vec’s anti-cancer effects.

Maud Brandely, Chief Medical Officer of Transgene, said: "This trial aims to first demonstrate that the regimen of our oncolytic virus Pexa-Vec plus ipilimumab is well tolerated. We expect that the intra-tumoral administration of ipilimumab will have less systemic toxicity thanks to its local administration. Another objective is to show the antitumor activity of the regimen in patients with advanced solid tumors which have exhausted all standard therapeutic options."

MabVax Therapeutics Studies Lead Investigational Drug MVT-5873 with Halozyme PEGPH20

On February 13, 2017 MabVax Therapeutics Holdings, Inc. (NASDAQ: MBVX), a clinical stage immuno-oncology drug development company, reported results from a pre-clinical study evaluating the potential benefits of using MabVax’s HuMab-5B1antibody, MVT-5873, currently in Phase I clinical trials for the treatment of metastatic pancreatic cancer with Halozyme Therapeutic’s (NASDAQ: HALO) investigational drug PEGPH20, which targets the tumor microenvironment potentially allowing increased access of co-administered cancer drug therapies to solid tumors (Press release, MabVax, FEB 13, 2017, View Source [SID1234517710]). PEGPH20 is currently in phase III clinical development for metastatic pancreatic cancer and in phase I clinical trials for non-small cell lung cancer, gastric cancer, and metastatic breast cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Results from the preclinical study were positive demonstrating improvement in accumulation of MVT-5873 on tumors in an animal model of pancreatic cancer when administered in sequence with PEGPH20.

"Initiating preclinical investigations of MVT-5873 in combination with Halozyme’s PEGPH20 provides a new potential treatment strategy combining the tumor penetration ability of PEGPH20 with the anti-tumor effects of MVT-5873," stated President and Chief Executive Officer J. David Hansen. "The initial pre-clinical collaboration combining our antibody with Halozyme’s unique therapy was encouraging and more comprehensive pre-clinical studies will now be undertaken. The potential of combining MVT-5873 with PEGPH20 could represent a significant step forward in the fight against pancreatic cancer. The results of these investigations will provide insight into broader applications of the PEGPH20 technology to other HuMab-5B1 programs including the Company’s immuno-PET imaging agent MVT-2163 that is also in phase I clinical trials, and the radioimmunotherapy product MVT-1075 that is planned for clinical evaluation early this year."

About MVT-5873
MVT-5873 is currently in a phase I clinical trial that is designed to establish safety and determine the recommended phase II dose both as monotherapy, and in combination with a standard of care chemotherapy using nab-paclitaxel plus gemcitabine. MabVax recently reported that the safety of MVT-5873 had been established at three incremental dose levels which was determined to be sufficient according to the protocol for investigators to begin enrolling and dosing patients with previously untreated pancreatic cancer receiving a standard of care chemotherapy.

Teva Reports Full Year and Fourth Quarter 2016 Financial Results

On February 13, 2017 Teva Pharmaceutical Industries Ltd. (NYSE: TEVA, TASE: TEVA) reported results for the year and the quarter ended December 31, 2016 (Press release, Teva, FEB 13, 2017, View Source [SID1234517709]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!



FY 2016
Q4 2016
Revenues $21.9 billion $6.5 billion
Cash flow from operations $5.2 billion $1.4 billion
GAAP EPS $0.07 ($1.10)
Non-GAAP EPS $5.14 $1.38


Teva reaffirms its 2017 full year non-GAAP guidance;
including revenues of $23.8 – 24.5 billion, and
non-GAAP EPS of $4.90 – 5.30
"2016 was a transitional year for Teva – one that included significant achievements, as well as challenges," stated Dr. Yitzhak Peterburg, Interim President and CEO of Teva. "While we continue to manage through a turbulent and constantly evolving industry, we are committed to execute against our strategy with more diversified revenue sources and profit streams, all backed by strong product development engines in both generics and specialty."
"In 2017, our main focus will be extracting synergies related to the Actavis Generics transaction, driving additional efficiencies throughout the organization, supporting cash generation and paying down our debt to maintain a strong balance sheet and delivering on the promise of the specialty pipeline and key generic launches. We are laser focused on execution at this critical juncture and are determined to deliver on our key priorities."
Dr. Peterburg continued, "With the entire Teva team, I am conducting a thorough review of the business to find additional opportunities to enhance value. Our management team is committed to delivering for our shareholders and unlocking the full potential of our pipeline and global business. We remain excited about the future as we strive to create a platform that supports continued growth and value creation for patients, shareholders and healthcare systems around the world."
2016 Annual Results
Revenues in 2016 were $21.9 billion, an increase of 11% compared to 2015, primarily due to the inclusion, following the closing on August 2, of the results of the Actavis Generics business.
Exchange rate differences between 2016 and 2015 decreased revenues by $174 million, decreased GAAP operating income by $81 million and decreased non-GAAP operating income by $55 million. In addition, the Venezuelan bolivar exchange rates that we used and inflation-driven price increases in Venezuela increased revenues by $526 million, increased GAAP operating income by $23 million and increased non-GAAP operating income by $133 million.
In light of the economic conditions in Venezuela, we exclude the 2016 increases in revenues and operating profit in any discussion of currency effects.
GAAP gross profit was $11.9 billion in 2016, up 4% compared to 2015. GAAP gross profit margin for the year was 54.1%, compared to 57.8% in 2015. Non-GAAP gross profit was $13.4 billion in 2016, up 10% compared to 2015. Non-GAAP gross profit margin was 61.3% in 2016, compared to 62.2% in 2015.
Research and Development (R&D) expenses in 2016 were $2.1 billion, an increase of 38% compared to 2015. R&D expenses excluding equity compensation expenses and purchase of in-process R&D in 2016 were $1.7 billion or 7.6% of revenues, compared to $1.4 billion, or 7.3% of revenues, in 2015. R&D expenses related to our generic medicines segment were $659 million, compared to $519 million in 2015. R&D expenses related to our specialty medicines segment were $998 million, compared to $918 million in 2015.
Selling and Marketing (S&M) expenses in 2016 were $3.9 billion, an increase of 11% compared to 2015. S&M expenses excluding amortization of purchased intangible assets and equity compensation expenses were $3.7 million, or 17.0% of revenues, in 2016, compared to $3.4 million, or 17.4% of revenues, in 2015. S&M expenses related to our generic medicines segment were $1.7 billion, an increase of 18% compared to $1.5 billion in 2015. S&M expenses related to our specialty medicines segment were $1.9 billion, a decrease of 1% compared to 2015.
General and Administrative (G&A) expenses in 2016 and in 2015 were $1.2 billion. G&A expenses excluding equity compensation expenses were $1.2 billion in 2016, or 5.4% of revenues, compared to $1.2 billion and 6.0% in 2015.
Operating income was $2.2 billion in 2016 compared to $3.4 billion in 2015. Non-GAAP operating income was $6.8 billion, up 11% compared to $6.2 billion in 2015.
Adjusted EBITDA (non-GAAP operating income, which excludes amortization and certain other items, and excluding depreciation expenses) for 2016 was $7.3 billion, up 11% compared to 2015.
In 2016, financial expenses were $1.3 billion, compared to $1.0 billion in 2015. Non-GAAP financial expenses were $442 million in 2016, compared to $223 million in 2015.
GAAP income tax expenses for 2016 were $521 million or 63% on pre-tax income of $824 million. In 2015, the provision for income taxes was $634 million or 27% on pre-tax income of $2.4 billion. The provision for non-GAAP income taxes for 2016 was $1.1 billion on pre-tax non-GAAP income of $6.4 billion, for an annual tax rate of 17%. The provision for non-GAAP income taxes in 2015 was $1.3 billion on pre-tax non-GAAP income of $6.0 billion, for an annual tax rate of 21%.
GAAP net income attributable to ordinary shareholders and GAAP diluted EPS were $68 million and $0.07, respectively, in 2016, compared to $1.6 billion and $1.82, respectively, in 2015. Non-GAAP net income attributable to ordinary shareholders for calculating diluted EPS and non-GAAP diluted EPS were $5.2 billion and $5.14, respectively in 2016, compared to $4.7 billion and $5.42 in 2015.
Non-GAAP information: Net non-GAAP adjustments in 2016 were $4.9 billion. Non-GAAP net income and non-GAAP EPS for the year were adjusted to exclude the following items:
amortization of purchased intangible assets totaling $993 million, of which $881 million is included in cost of goods sold and the remaining $112 million in selling and marketing expenses;
an impairment of goodwill of $900 million, relating to the acquisition of Rimsa;
legal settlements and loss contingencies of $899 million, primarily $519 million in connection with the FCPA settlement with the DOJ and SEC and $225 million in connection with the ciprofloxacin (Cipro) settlement;
financial expenses of $888 million, including $746 million related to the impairment of our monetary balance sheet items in Venezuela following our decisions to adopt different exchange rates and $99 million related to the impairment of our investment in Mesoblast;
impairment of long-lived assets of $746 million, mainly related to Revascor and Zecuity ($506 million) and to an impairment of property, plant and equipment ($149 million);
R&D-related expenses of $423 million, comprised mainly of an upfront payment of $250 million to Regeneron pursuant to our collaborative agreement to develop and commercialize its pain medication product fasinumab and an upfront payment of $160 million to Celltrion pursuant to our exclusive partnership to commercialize two of Celltrion’s biosimilar products;
inventory step-up of $383 million, related mainly to the acquisition of the Actavis Generics business;
acquisition and integration expenses of $261 million;
restructuring expenses of $245 million;
costs related to regulatory actions taken in facilities of $153 million;
cost of sales adjustment of $133 million, to adjust our inventory balance in Venezuela to reflect the U.S. dollar fair market value of the inventory;
equity compensation of $121 million;
contingent consideration of $83 million;
other non-GAAP items of $49 million;
net gain of $693 million from the divestments of products in connection with the acquisition of the Actavis Generics business;
minority interest adjustment of negative $76 million; and
related tax effect of $593 million.
Teva believes that excluding such items facilitates investors’ understanding of its business. See the attached tables for a reconciliation of the U.S. GAAP results to the adjusted non-GAAP figures.
Cash flow from operations generated during 2016 was $5.2 billion, down 6% compared to $5.5 billion in 2015. Free cash flow, excluding net capital expenditures, was $4.4 billion compared to $4.9 billion in 2015, a decrease of 11%.
Total balance sheet assets were $92.9 billion as of December 31, 2016, compared to $98.7 billion as of September 30, 2016 and $54.2 billion at December 31, 2015. The decrease from September 30, 2016 was mainly due to a decrease of $8.1 billion in identifiable intangible assets, partially offset by an increase of $4.1 billion of goodwill, both related mainly to the Actavis and Rimsa acquisitions.
Cash and investments at December 31, 2016 decreased to $1.9 billion, compared to $2.7 billion at September 30, 2016 and $8.4 billion at December 31, 2015.
As of December 31, 2016, our debt was $35.8 billion, a decrease of $1.1 billion compared to $36.9 billion as of September 30, 2016 and $9.9 billion at December 31, 2015. The portion of total debt classified as short-term as of December 31, 2016 was 9%.
Total shareholders’ equity was $35.0 billion at December 31, 2016, compared to $37.0 billion at September 30, 2016 and $29.9 billion at December 31, 2015.
Fourth Quarter 2016 Results
Revenues in the fourth quarter of 2016 were $6.5 billion, up 33% compared to the fourth quarter of 2015, primarily due to the inclusion, following the closing on August 2, of the results of the Actavis Generics business.
Exchange rate differences between the fourth quarter of 2016 and the fourth quarter of 2015 decreased revenues by $41 million, decreased GAAP operating income by $14 million and decreased non-GAAP operating income by $9 million. In addition, the Venezuelan bolivar exchange rates that we used and inflation-driven price increases in Venezuela increased revenues by $184 million, decreased GAAP operating income by $34 million and increased non-GAAP operating income by $75 million.
In light of the economic conditions in Venezuela, we exclude the 2016 changes in revenues and operating profit in any discussion of currency effects.
GAAP gross profit was $3.4 billion in the fourth quarter of 2016, up 19% compared to the fourth quarter of 2015. GAAP gross profit margin was 52.2% in the quarter, compared to 58.3% in the fourth quarter of 2015. Non-GAAP gross profit was $3.9 billion in the fourth quarter of 2016, up 26% from the fourth quarter of 2015. Non-GAAP gross profit margin was 59.4% in the fourth quarter of 2016, compared to 62.6% in the fourth quarter of 2015.
Research and Development (R&D) expenses for the fourth quarter of 2016 were $684 million, up 53% compared to the fourth quarter of 2015 mainly due to higher R&D expenses for both generics and specialty, as well as the upfront payment of $160 million to Celltrion. R&D expenses excluding equity compensation expenses and purchase of in-process R&D in the fourth quarter of 2016 were $514 million or 7.9% of quarterly revenues, compared to $395 million or 8.1% in the fourth quarter of 2015. R&D expenses related to our generic medicines segment were $211 million, compared to $133 million in the fourth quarter of 2015, an increase of 59%, mainly due to the inclusion of expenses of the Actavis Generics business. R&D expenses related to our specialty medicines segment were $296 million, an increase of 13% compared to $263 million in the fourth quarter of 2015, mainly due to increased spending on our late-stage compound for the treatment of migraine, TEV-48125 (fremanezumab).
Selling and Marketing (S&M) expenses in the fourth quarter of 2016 were $1.1 billion, an increase of 23% compared to the fourth quarter of 2015. S&M expenses excluding amortization of purchased intangible assets and equity compensation expenses were $1.1 billion, or 17.0% of revenues, in the fourth quarter of 2016, compared to $898 million, or 18.4% of revenues, in the fourth quarter of 2015. S&M expenses related to our generic medicines segment were $549 million, an increase of 60% compared to $343 million in the fourth quarter of 2015, mainly due to additional costs related to the inclusion of the Actavis Generics business from August 2016 and the launch of our business venture in Japan in the second quarter of 2016. S&M expenses related to our specialty medicines segment were $506 million, a decrease of 10% compared to $561 million in the fourth quarter of 2015. The decrease was mainly due to decreased investment in specific products such as Nuvigil, which is facing generic competition, and Zecuity, which was withdrawn from the market.
General and Administrative (G&A) expenses in the fourth quarter of 2016 were $311 million, compared to $291 million in the fourth quarter of 2015. G&A expenses excluding equity compensation expenses were $294 million in the fourth quarter of 2016, or 4.5% of revenues, compared to $280 million and 5.7% in the fourth quarter of 2015.
Quarterly GAAP operating loss was $0.1 billion in the fourth quarter of 2016, compared to income of $0.9 billion in the fourth quarter of 2015. Quarterly non-GAAP operating income was $1.9 billion, up 31%, compared to $1.5 billion in the fourth quarter of 2015.
Adjusted EBITDA (non-GAAP operating income, which excludes amortization and certain other items, and excluding depreciation expenses) was $2.1 billion, up 31%, compared to $1.6 billion in the fourth quarter of 2015.
GAAP financial expenses for the fourth quarter of 2016 were $777 million, compared to $70 million in the fourth quarter of 2015. This increase is mainly the result of an impairment of $500 million of our monetary balance sheet items in Venezuela following our decision to begin utilizing a blended exchange rate effective on December 1, 2016, as well as higher interest expenses. Non-GAAP financial expenses were $233 million in the fourth quarter of 2016, compared to $68 million in the fourth quarter of 2015.
GAAP income tax expenses for the fourth quarter of 2016 were $57 million on pre-tax loss of $914 million. In the fourth quarter of 2015, the provision for income taxes was $249 million, or 29% on pre-tax income of $861 million. The provision for non-GAAP income taxes for the fourth quarter of 2016 was $218 million on pre-tax non-GAAP income of $1.7 billion, for a quarterly tax rate of 13%. The provision for non-GAAP income taxes in the fourth quarter of 2015 was $289 million on pre-tax non-GAAP income of $1.4 billion, for a quarterly tax rate of 21%.
GAAP net loss attributable to ordinary shareholders and GAAP diluted EPS were $1.0 billion and a loss of $1.10, respectively, in the fourth quarter of 2016, compared to income of $500 million and EPS of $0.55 in the fourth quarter of 2015. Non-GAAP net income attributable to ordinary shareholders for calculating diluted EPS and non-GAAP diluted EPS were $1.5 billion and $1.38, respectively, in the fourth quarter of 2016, compared to $1.1 billion and $1.28 in the fourth quarter of 2015.
For the fourth quarter of 2016, the weighted average outstanding shares for the fully diluted earnings per share calculation was 1,015 million on a GAAP basis and 1,076 million on a non-GAAP basis. The number of average weighted diluted shares outstanding used for the fully diluted share calculation for the fourth quarter of 2015 was 875 million shares on a GAAP and 888 million on a non-GAAP basis. The increase in the number of shares resulted from our December 2015 equity offerings and from the issuance of shares to Allergan in August 2016 in connection with the closing of the Actavis Generics acquisition. The number of shares on a non-GAAP basis includes the potential dilution resulting from our mandatory convertible preferred shares, which had a dilutive effect on our non-GAAP earnings per share.
As of December 31, 2016, the fully diluted share count for calculating Teva’s market capitalization was approximately 1,079 million shares.
Non-GAAP information: Net non-GAAP adjustments in the fourth quarter of 2016 were $2.5 billion. Non-GAAP net income and non-GAAP EPS for the quarter were adjusted to exclude the following items:
an impairment of goodwill of $900 million, relating to the acquisition of Rimsa;
financial expenses of $544 million, primarily $500 million related to the impairment of our monetary balance sheet items in Venezuela following our decision to adopt a blended exchange rate;
legal settlements and loss contingencies of $225 million in connection with the ciprofloxacin (Cipro) settlement;
amortization of purchased intangible assets totaling $182 million, of which $170 million is included in cost of goods sold and the remaining $12 million in selling and marketing expenses. Amortization expenses were particularly low this quarter due to the impact of the changes in the value of the Actavis and Rimsa intangible assets;
R&D-related expenses of $161 million, comprised mainly of an upfront payment of $160 million to Celltrion pursuant to our exclusive partnership to commercialize two of Celltrion’s biosimilar products;
inventory step-up of $140 million, related mainly to the acquisition of the Actavis Generics business;
cost of sales adjustment of $133 million, to adjust our inventory balance in Venezuela to reflect the U.S. dollar fair market value of the inventory;
impairment of long-lived assets of $132 million, $80 million of which was related to our facility in Godollo, Hungary;
restructuring expenses of $91 million;
acquisition, integration and related expenses including contingent consideration of $75 million;
equity compensation expenses of $38 million;
costs related to regulatory actions taken in facilities of $30 million;
other non-GAAP items of negative $26 million;
minority interest adjustment of negative $11 million; and
related tax effect of $161 million.
Teva believes that excluding such items facilitates investors’ understanding of its business. See the attached tables for a reconciliation of the GAAP results to the adjusted non-GAAP figures.
Cash flow from operations generated during the fourth quarter of 2016 was $1.4 billion, a decrease of 12% compared to the fourth quarter of 2015 mainly due to changes in our working capital. Free cash flow, excluding net capital expenditures, was $1.1 billion, down 19% compared to the fourth quarter of 2015.
Segment Results for the Fourth Quarter 2016
Beginning in the fourth quarter of 2016, and following the acquisition of Actavis Generics, we revised our segment structure so that our generic medicines segment, which includes chemical and therapeutic equivalents of originator medicines in a variety of dosage forms, now includes our OTC business, conducted primarily through PGT, as well as our API manufacturing business.
All data presented has been conformed to the new segment structure.
Generic Medicines Segment
Three Months Ended December 31,
2016 2015
U.S.$ in millions / % of Segment Revenues

Revenues $ 3,716 100.0% $ 2,573 100.0%
Gross profit 1,835 49.4% 1,169 45.4%
R&D expenses 211 5.7% 133 5.2%
S&M expenses 549 14.8% 343 13.3%
Segment profit* $ 1,075 28.9% $ 693 26.9%

*Segment profit consists of gross profit for the segment, less R&D and S&M expenses related to the segment. Segment profit does not include G&A expenses, amortization, inventory step up and certain other items.
Generic Medicines Revenues
Generic medicines revenues in the fourth quarter of 2016 were $3.7 billion, an increase of 44% compared to the fourth quarter of 2015, reflecting the results of the Actavis Generics business from August 2, 2016.
Generic revenues consisted of:
U.S. revenues of $1.4 billion, an increase of 40% compared to the fourth quarter of 2015, mainly due to the inclusion of Actavis Generics with revenues of $630 million.
European revenues of $1.1 billion, an increase of 33%, or 38% in local currency terms, compared to the fourth quarter of 2015, mainly due to the inclusion of Actavis Generics with revenues of $360 million.
ROW revenues of $1.3 billion, an increase of 62%, or 36% in local currency terms, compared to the fourth quarter of 2015. The increase in local currency terms was mainly due to the results of our business venture with Takeda in Japan which commenced operations in April 2016, and the inclusion of $150 million of revenues from Actavis Generics.
Our OTC revenues (which are included in the market revenues above) were $412 million, an increase of 28% compared to $321 million in the fourth quarter of 2015. In local currency terms, revenues increased 7%. PGT’s in-market sales were $530 million in the fourth quarter of 2016, compared to $450 million in the fourth quarter of 2015.
API sales to third parties of $181 million (which are included in the market revenues above), a decrease of 10%, compared to the fourth quarter of 2015, mainly as sales to Actavis Generics are no longer classified as sales to third parties.
Generic medicines revenues comprised 57% of our total revenues in the quarter, compared to 53% in the fourth quarter of 2015.
Generic Medicines Gross Profit
Gross profit of our generic medicines segment in the fourth quarter of 2016 was $1.8 billion, an increase of 57% compared to $1.2 billion in the fourth quarter of 2015. The higher gross profit was mainly a result of the inclusion of Actavis Generics and our business venture with Takeda in Japan, both of which impacted the current quarter but not the fourth quarter of 2015.
Gross profit margin for our generic medicines segment in the fourth quarter of 2016 increased to 49.4%, from 45.4% in the fourth quarter of 2015.
Generic Medicines Profit
Our generic medicines segment generated profit of $1.1 billion in the fourth quarter of 2016, an increase of 55% compared to the fourth quarter of 2015. Generic medicines profitability as a percentage of generic medicines revenues was 28.9% in the fourth quarter of 2016, up from 26.9% in the fourth quarter of 2015.
Specialty Medicines Segment
Three Months Ended December 31,
2016 2015
U.S.$ in millions / % of Segment Revenues

Revenues $ 2,203 100.0% $ 2,114 100.0%
Gross profit 1,926 87.4% 1,855 87.7%
R&D expenses 296 13.4% 263 12.4%
S&M expenses 506 23.0% 561 26.5%
Segment profit* $ 1,124 51.0% $ 1,031 48.8%


*Segment profit consists of gross profit for the segment, less R&D and S&M expenses related to the segment. Segment profit does not include G&A expenses, amortization, inventory step up and certain other items.
Specialty Medicines Revenues
Specialty medicines revenues in the fourth quarter of 2016 were $2.2 billion, up 4% compared to the fourth quarter of 2015. U.S. specialty medicines revenues were $1.7 billion, up 5% compared to the fourth quarter of 2015. European specialty medicines revenues were $384 million, an increase of 5%, or 9% in local currency terms, compared to the fourth quarter of 2015. ROW specialty revenues were $102 million, down 6%, or 4% in local currency terms, compared to the fourth quarter of 2015.
Specialty medicines revenues comprised 34% of our total revenues in the quarter, compared to 43% in the fourth quarter of 2015.
The following table presents revenues by therapeutic area and key products for our specialty medicines segment for the three months ended December 31, 2016 and 2015:

Three Months Ended
December 31,
Percentage
Change
2016 2015 2016 – 2015
U.S. $ in millions
CNS $ 1,243 $ 1,274 (2%)
Copaxone 1,015 960 6%
Azilect 88 80 10%
Nuvigil 25 100 (75%)
Respiratory 325 326 (0%)
ProAir 139 148 (6%)
QVAR 116 119 (3%)
Oncology 268 318 (16%)
Treanda and Bendeka 150 198 (24%)
Women’s Health 122 107 14%
Other Specialty 245 89 175%
Total Specialty Medicines $ 2,203 $ 2,114 4%

Global revenues of Copaxone (20 mg/mL and 40 mg/mL), the leading multiple sclerosis therapy in the U.S. and globally, were $1.0 billion, an increase of 6% compared to the fourth quarter of 2015.
Copaxone revenues in the United States were $829 million, up 9% compared to $760 million in the fourth quarter of 2015, mainly due to a price increase of 7.9% in January 2016. At the end of the fourth quarter of 2016, according to December 2016 IMS data, our U.S. market shares for the Copaxone products in terms of new and total prescriptions were 27.9% and 29.3%, respectively. Copaxone 40 mg/mL accounted for over 84% of total Copaxone prescriptions in the U.S.
Copaxone revenues outside the United States were $186 million, a decrease of 7%, compared to the fourth quarter of 2015 mainly due to loss of tender orders in Russia, partially offset by a volume increase in Europe.
Our global Azilect revenues were $88 million, an increase of 10% compared to the fourth quarter of 2015. Global in-market sales decreased 31%, mainly due to generic competition in certain European markets.
Revenues of our respiratory products were $325 million, in line with results in the fourth quarter of 2015. ProAir revenues in the quarter were $139 million, down 6% compared to the fourth quarter of 2015, due to lower volumes related to changes in our market access. QVAR global revenues were $116 million in the fourth quarter of 2016, down 3% compared to the fourth quarter of 2015, mainly due to net pricing effects.
Revenues of our oncology products were $268 million in the fourth quarter of 2016, down 16% compared to the fourth quarter of 2015. Revenues of Treanda and Bendeka were $150 million, down 24% compared to the fourth quarter of 2015, due to increased competition from other therapies and normalization of inventory levels following the launch of Bendeka.
Specialty Medicines Gross Profit
Gross profit of our specialty medicines segment was $1.9 billion, up 4% compared to the fourth quarter of 2015. Gross profit margin for our specialty medicines segment in the fourth quarter of 2016 was 87.4%, compared to 87.7% in the fourth quarter of 2015.
Specialty Medicines Profit
Our specialty medicines segment profit was $1.1 billion in the fourth quarter of 2016, up 9% compared to the fourth quarter of 2015.
Specialty medicines profit as a percentage of segment revenues was 51.0% in the fourth quarter of 2016, up from 48.8% in the fourth quarter of 2015.
The following tables present information regarding our multiple sclerosis franchise and of our other specialty medicines for the three months ended December 31, 2016 and 2015:

Multiple Sclerosis
Three months ended December 31,
2016 2015
U.S.$ in millions / % of MS Revenues

Revenues $ 1,015 100.0% $ 960 100.0%
Gross profit 927 91.3% 866 90.2%
R&D expenses 30 3.0% 32 3.3%
S&M expenses 81 7.9% 121 12.6%
MS profit $ 816 80.4% $ 713 74.3%


Other Specialty
Three months ended December 31,
2016 2015
U.S.$ in millions / % of Other Specialty Revenues

Revenues $ 1,188 100.0% $ 1,154 100.0%
Gross profit 999 84.1% 989 85.7%
R&D expenses 266 22.4% 231 20.0%
S&M expenses 425 35.8% 440 38.1%
Other Specialty profit $ 308 25.9% $ 318 27.6%

Other Activities
Other revenues, primarily sales of third-party products for which we act as distributor, mostly in the United States via Anda, as well as in Israel and Hungary, sales of medical devices, contract manufacturing services related to products divested in connection with the Actavis Generics acquisition and other miscellaneous items, were $573 million in the fourth quarter of 2016, compared to $194 million, in the fourth quarter of 2015. The increase was mainly related to the inclusion of Anda’s revenues beginning in the fourth quarter of 2016.
Revenues of our other activities comprised 9% of our total revenues in the quarter, compared to 4% in the fourth quarter of 2015.
Outlook for 2017 Non-GAAP Results
Teva reaffirms its 2017 full year non-GAAP guidance, including the items below:
We expect revenues for full year 2017 to be $23.8 – 24.5 billion.
Non-GAAP EPS for 2017 is expected to be $4.90 – 5.30, based on a weighted average number of shares of 1,076 million.
These estimates reflect management`s current expectations for Teva’s performance in 2017. Actual results may vary, whether as a result of exchange rate differences, market conditions or other factors. In addition, the non-GAAP figures exclude the amortization of purchased intangible assets, costs related to certain regulatory actions, inventory step-up, legal settlements and reserves, impairments and related tax effects.
Dividends
On February 7, 2017, the Board of Directors declared a cash dividend of $0.34 per ordinary share for the fourth quarter of 2016. For holders of our ordinary shares that are traded on the Tel Aviv Stock Exchange, the dividend will be converted into new Israeli shekels based on the official exchange rate as of February 13, 2017. The record date will be March 2, 2017, and the payment date will be March 20, 2017. Tax will be withheld at a rate of 15%.
Also, on February 7, 2017, the Board of Directors declared a cash dividend of $17.50 per mandatory convertible preferred share for the fourth quarter of 2016. The record date will be March 1, 2017 and the payment date will be March 15, 2017. Tax will be withheld at a rate of 15%.