On April 17, 2018 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported updated durable response data from the Phase 1 study involving patients with high-grade glioma who received Toca 511 & Toca FC at the time of surgical resection will be presented at the 2018 American Academy of Neurology (AAN) Annual Meeting and 2018 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting. Previously disclosed clinical data will also be reviewed at these meetings (Press release, Tocagen, APR 17, 2018, View Source;p=RssLanding&cat=news&id=2342917 [SID1234525819]).

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Additionally, preclinical data describing the level of Toca 511 transduction required for an anti-tumor response will be presented at the 14th Annual PEGS: The Essential Protein Engineering Summit.

Details of the presentation at AAN, held April 21-27 in Los Angeles, are as follows. The full presentation will be placed on Tocagen’s website following the presentation.

Presentation Type: Oral presentation (Abstract: 1173)
Title: Toca 511 & Toca FC: Evaluation of durable response rate in the post-resection setting and association with survival in patients with recurrent high grade glioma
Presenter: Timothy Cloughesy, M.D., director of the University of California, Los Angeles, Neuro-Oncology Program
Date and Time: Tuesday, April 24, 2:00 p.m. – 2:12 p.m. PT

Details of the presentation at the AANS Annual Scientific Meeting, held April 28-May 2 in New Orleans, are as follows:

Presentation Type: Oral presentation (Abstract: 615)
Title: Evaluation of durable response rate in the post-resection setting and association with survival in patients with recurrent high grade glioma who received Toca 511 and Toca FC treatment
Presenter: Bob S. Carter, M.D., Ph.D., chief of the Massachusetts General Hospital department of neurosurgery
Date and Time: Tuesday, May 1, 11:32 a.m. – 11:42 a.m. CT

Details of the presentation at PEGS, held April 30-May 4 in Boston, are as follows. The full presentation will be placed on Tocagen’s website following the presentation.

Presentation Type: Oral presentation
Title: Replicating retroviruses for manipulation of the tumor immune ecosystem: preclinical and clinical outcomes
Presenter: Douglas Jolly, Ph.D., executive vice president of research and pharmaceutical development at Tocagen
Date and Time: Tuesday, May 1, 8:30 – 9:00 a.m. ET

About Toca 511 & Toca FC

Tocagen’s lead product candidate is a two-part cancer-selective immunotherapy comprised of an investigational biologic, Toca 511, and an investigational small molecule, Toca FC. Toca 511 is a retroviral replicating vector (RRV) that selectively infects cancer cells and delivers a gene for the enzyme, cytosine deaminase (CD). Through this targeted delivery, infected cancer cells carry the CD gene and produce CD. Toca FC is an orally administered prodrug, 5-fluorocytosine (5-FC), which is converted into an anti-cancer drug, 5-fluorouracil (5-FU), when it encounters CD. 5-FU kills cancer cells and immune-suppressive myeloid cells in the tumor microenvironment resulting in anti-cancer immune activation and subsequent tumor killing.

On April 17, 2018 Rigel Pharmaceuticals, Inc. reported that the U.S. Food and Drug Administration (FDA) approved TAVALISSE (fostamatinib disodium hexahydrate) for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment (Press release, Rigel, APR 17, 2018, View Source [SID1234605501]). TAVALISSE is an oral spleen tyrosine kinase (SYK) inhibitor that targets the underlying autoimmune cause of the disease by impeding platelet destruction, providing an important new treatment option for adult patients with chronic ITP. Rigel plans to launch TAVALISSE in the United States in late May 2018.

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"Chronic ITP is challenging to treat because the heterogeneity of the disease makes it difficult to predict how an individual patient will respond to available treatments and not all patients can find a treatment that works well for them," said James Bussel, M.D., professor emeritus of pediatrics at Weill Cornell Medicine and the principal study investigator on the FIT Phase 3 program. Dr. Bussel has served as a consultant and paid member of the advisory board for Rigel Pharmaceuticals, Inc. "The FDA approval of fostamatinib arms physicians with a new treatment option, which works via a novel mechanism."

The FDA approval of TAVALISSE was supported by data from the FIT clinical program, which included two randomized placebo-controlled Phase 3 trials (Studies 047 and 048) and an open-label extension (Study 049), as well as an initial proof of concept study. The New Drug Application (NDA) included data from 163 ITP patients and was supported by a safety database of more than 4,600 subjects across other indications in which fostamatinib has been evaluated.

"People living with chronic ITP often feel they have an invisible disease — one that can not only impact quality of life, but also be life threatening," said Caroline Kruse, executive director of the Platelet Disorder Support Association, a patient advocacy organization dedicated to ITP patients. "That’s why we encourage members of our community to learn about their disease, understand treatment strategies, and seek support so that they can advocate for their best care. The availability of a new treatment option provides the ITP community with more choices."

Different Treatment Approach
TAVALISSE is designed to inhibit SYK, a key signaling component in the body’s immune process that can lead to platelet destruction in ITP patients. TAVALISSE may address an underlying autoimmune cause of ITP by impeding platelet destruction.

"We are excited to bring this new medicine to the population of adult patients with chronic ITP in need of additional therapies. I want to thank the patients, caregivers and physicians who contributed to our fostamatinib clinical program, and also the Rigel team for all of their dedication and hard work to bring the company to this historic day," said Raul Rodriguez, president and CEO of Rigel Pharmaceuticals. "This regulatory milestone, our first product approval, validates the therapeutic effect of SYK inhibition in an autoimmune disease."

Rigel will be providing product information at the ASCO (Free ASCO Whitepaper) Annual Meeting being held June 1-5, 2018 in Chicago, Booth #24160, or you can visit www.TAVALISSE.com.

About ITP
In patients with ITP, the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP include excessive bruising, bleeding and fatigue. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPOs) and splenectomy. However, not all patients have an adequate treatment response with existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSE.com for full Prescribing Information.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

Trademarks for TAVALISSE are owned by or licensed by Rigel.

Conference Call and Webcast Today at 5:00PM Eastern Time
Rigel will hold a live conference call and webcast today at 5:00pm Eastern Time (2:00pm Pacific Time).

Participants can access the live conference call by dialing (855) 892-1489 (domestic) or (720) 634-2939 (international) and using the Conference ID number 5189918. The slide presentation accompanying the conference call can be accessed from Rigel’s website at www.rigel.com/webcasts. The webcast will be archived and available for replay after the call via the Rigel website.

On April 17, 2018 Johnson & Johnson (NYSE: JNJ) reported sales of $20.0 billion for the first quarter of 2018, an increase of 12.6% as compared to the first quarter of 2017 (Press release, Johnson & Johnson, APR 17, 2018, View Source [SID1234525423]).

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Operational sales results increased 8.4% and the positive impact of currency was 4.2%. Domestic sales increased 6.1%. International sales increased 19.9%, reflecting operational growth of 10.9% and a positive currency impact of 9.0%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 4.3%, domestic sales increased 1.3% and international sales increased 7.6%.*

Net earnings and diluted earnings per share for the first quarter of 2018 were $4.4 billion and $1.60, respectively. First-quarter 2018 net earnings included after-tax intangible amortization expense of approximately $1.0 billion and a charge for after-tax special items of approximately $0.3 billion. First-quarter 2017 net earnings included after-tax intangible amortization expense of approximately $0.2 billion and a charge for after-tax special items of approximately $0.4 billion. Excluding after-tax intangible amortization expense and special items, adjusted net earnings for the current quarter were $5.6 billion and adjusted diluted earnings per share were $2.06, representing increases of 11.8% and 12.6%, respectively, as compared to the same period in 2017.* On an operational basis, adjusted diluted earnings per share also increased 5.5%.* A reconciliation of non-GAAP financial measures is included as an accompanying schedule.

"We are pleased with the strong and consistent performance delivered by our colleagues around the world, demonstrated by our sales and EPS growth in the first quarter," said Alex Gorsky, Chairman and Chief Executive Officer. "Our Pharmaceutical business continues to deliver robust growth and we are pleased with the improvement in our Consumer business. In our Medical Devices businesses, we have areas of leadership and continue to make investments and portfolio choices to improve performance."
Mr. Gorsky continued, "The U.S. tax legislation passed late last year is creating the opportunity for us to invest more than $30 billion in R&D and capital investments in the U.S. over the next four years, which is an increase of 15%."
The Company increased its sales guidance for the full-year 2018 to a range of $81.0 to $81.8 billion, reflecting expected operational growth in the range of 4.0% to 5.0%. Additionally, the Company reaffirmed its adjusted earnings guidance for full-year 2018 to a range of $8.00 to $8.20 per share, reflecting expected operational growth in the range of 6.8% to 9.6%.

Segment Sales Performance
Worldwide Consumer sales of $3.4 billion for the first quarter 2018 represented an increase of 5.3% versus the prior year, consisting of an operational increase of 1.3% and a positive impact from currency of 4.0%. Domestic sales increased 1.6%, international sales increased 8.2%, which reflected an operational increase of 1.2% and a positive currency impact of 7.0%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 2.0%, domestic sales increased 1.6% and international sales increased 2.3%*.
Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by beauty products primarily NEUTROGENA, AVEENO, and Dr. Ci Labo, and international analgesics in over-the-counter products, partially offset by the negative impact of domestic baby care products.
Worldwide Pharmaceutical sales of $9.8 billion for the first quarter 2018 represented an increase of 19.4% versus the prior year with an operational increase of 15.1% and a positive impact from currency of 4.3%. Domestic sales increased 9.9%; international sales increased 33.1%, which reflected an operational increase of 22.5% and a positive currency impact of 10.6%. Sales included the impact of Actelion Ltd which contributed 7.6%, to worldwide operational sales growth. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 7.5%, domestic sales increased 2.2% and international sales increased 15.3%.*

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by new products and the strength of core products. Strong growth in new products include DARZALEX (daratumumab), for the treatment of patients with multiple myeloma, IMBRUVICA (ibrutinib), an oral, once-daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer and TREMFYA (guselkumab), for the treatment of adults living with moderate to severe plaque psoriasis. Additional contributors to operational sales growth included ZYTIGA (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer, STELARA (ustekinumab) and international SIMPONI/SIMPONI ARIA (golimumab), biologics for the treatment of a number of immune-mediated inflammatory diseases, XARELTO (rivaroxaban), an oral anticoagulant, and INVEGA SUSTENNA/XEPLION/TRINZA/TREVICTA (paliperidone palmitate), long-acting, injectable atypical antipsychotics for the treatment of schizophrenia in adults.

During the quarter, the U.S. Food and Drug Administration (FDA) approved an additional indication for ZYTIGA (abiraterone acetate), in combination with prednisone for the treatment of patients with metastatic high-risk castration-sensitive prostate cancer and ERLEADA (apalutamide) an oral androgen receptor inhibitor for the treatment of patients with non-metastatic castration-resistant prostate cancer. In addition, the Committee for Medicinal Products for Human Use issued a positive opinion recommending marketing authorization for JULUCA (rilpivirine and dolutegravir), the first, single-pill, two-drug regimen for the treatment of human immunodeficiency virus type 1 infection.

Also in the quarter, a marketing authorization application was submitted to the European Medicines Agency for apalutamide, an oral androgen receptor inhibitor for the treatment of patients with high-risk non-metastatic castration-resistant prostate cancer.

Worldwide Medical Devices sales of $6.8 billion for the first quarter 2018 represented an increase of 7.5% versus the prior year consisting of an operational increase of 3.2% and a positive currency impact of 4.3%. Domestic sales increased 2.2%; international sales increased 12.7%, which reflected an operational increase of 4.2% and a positive currency impact of 8.5%. Sales included the partial quarter impact of the recently acquired surgical vision business which contributed 3.1%, to worldwide operational sales growth. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 1.1%, domestic sales decreased 0.2% and international sales increased 2.4%.*

Worldwide operational results, excluding the net impact of acquisitions and divestitures, were driven by ACUVUE contact lenses in the Vision Care business; electrophysiology products in the Interventional Solutions business; endocutters in the Advanced Surgery business; and trauma products in the Orthopaedics business, partially offset by declines in the Diabetes Care business and spine products in the Orthopaedics business.
During the quarter, the acquisition of Orthotaxy S.A.S., a privately-held developer of software-enabled surgery technologies, including a differentiated robotic-assisted surgery was completed. In addition, the Company announced a binding offer from Platinum Equity, a private investment firm, to acquire its LifeScan business for approximately $2.1 billion, subject to customary adjustments.

Subsequent to the quarter, ACUVUE OASYS with Transitions received 510(k) clearance from the FDA and is indicated for vision correction and the attenuation of bright light.
Additionally, Johnson & Johnson plans to implement actions across its global supply chain that are intended to enable the company to focus resources and increase investments in critical capabilities, technologies and solutions necessary to manufacture and supply its product portfolio of the future, enhance agility and drive growth. The Company expects these supply chain actions will include expanding our use of strategic collaborations, and bolstering our initiatives to reduce complexity, improving cost-competitiveness, enhancing capabilities and optimizing our network. Discussions regarding specific future actions are ongoing and are subject to all relevant consultation requirements before they are finalized.

In total, the Company expects these actions to generate approximately $0.6 to $0.8 billion in annual pre-tax cost savings that will be substantially delivered by 2022. The Company expects to record pre-tax restructuring charges of approximately $1.9 to $2.3 billion, which will be treated as a special item.

On April 17, 2018 Euronext Paris: FR0010331421 – IPH) reported preliminary data from an ongoing Phase I/II trial evaluating the safety and efficacy of the combination of monalizumab, a first-in-class monoclonal antibody targeting NK checkpoint receptor NKG2A, with cetuximab (anti-EGFR) in previously treated patients with recurrent and/or metastatic squamous cell carcinoma of the head & neck (R/M SCCHN) (Press release, Innate Pharma, APR 17, 2018, View Source [SID1234525441]). These data are highlighted in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, April 14-18, in Chicago.

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Roger B. Cohen, Prof. of Medicine at the Hospital of the University of Pennsylvania, Associate Director of Clinical Research, Abramson Cancer Center Philadelphia and the lead investigator of the study, commented: "The data so far show that this therapy is active in patients with advanced head and neck cancer. The activity of cetuximab in patients previously treated with platinum salts is limited, with a response rate of around 13%. The addition of monalizumab appears to increase the response rate without potentiating the side effects of cetuximab. Since monalizumab targets a checkpoint that is different from other currently targeted immune checkpoints, it’s an interesting option as a combination partner for a variety of novel immunotherapeutic approaches".

Pierre Dodion, Chief Medical Officer of Innate Pharma, added: "While PD-1/L1 therapy is quickly changing the treatment paradigm of SCCHN, there remains a high unmet medical need for the majority of patients who don’t benefit from checkpoint inhibitor therapy. These preliminary data support further investigation of this novel combination in third line recurrent and metastatic SCCHN. We look forward to sharing updated data from the ongoing trial at medical conferences during 2018."

The highest dose tested for monalizumab in the dose-escalation portion of the study (10 mg/kg every 2 weeks) was given in combination with the approved dose and schedule of cetuximab (400 mg/m² load, then 250 mg/m² weekly) in the Phase II cohort expansion. Patients could be either HPV (-) or HPV (+) and had progressed after platinum-based therapy with a maximum of 2 prior systemic treatment regimens for R/M disease. Prior cetuximab treatment (when used for the definitive treatment of locally advanced disease in combination with radiation) and prior immuno-oncology (IO) therapy were allowed.

Among the 31 patients enrolled in the expansion part, the combination was well tolerated, consistent with previously presented data at AACR (Free AACR Whitepaper) 2017, with no additional safety concerns compared to monalizumab or cetuximab given alone. The majority of adverse events (AE) were of Grade 1-2 severity, rapidly reversible and easily manageable. No infusion-related reactions or treatment-related deaths occurred. The most frequent AEs (skin disorders) described with cetuximab were not potentiated by the combination with monalizumab.
Among the patients enrolled, as per study design, all had been previously treated with platin-containing regimens. In addition, 14 patients had been previously treated with PD-1 antibodies and 3 with prior cetuximab.
Twenty-six patients were evaluable for efficacy; the other 5 patients are too early on study to have had a post-baseline assessment. At the cut-off date of March 9, 2018, there were 8 confirmed RECIST partial responses (31%) with median time to follow-up of 129 days, achieving the predefined number of 8 responses needed to declare the trial positive. 14 patients (54%) had stable disease. Median duration of response has not yet been reached; six responders are still on treatment. The trial has now enrolled all planned patients (n=40). Further follow-up is needed to evaluate the duration of response, progression-free survival (PFS) and overall survival (OS).

Genprex has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Genprex, 2018, APR 17, 2018, View Source [SID1234527531]).

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