On July 16, 2019 Puma Biotechnology, Inc. (Nasdaq: PBYI) announced that its licensing partner Knight Therapeutics Inc. (Knight) has received marketing authorization from Health Canada to commercialize NERLYNX (neratinib) in Canada for the extended adjuvant treatment of women with early stage hormone receptor positive, HER2-overexpressed/amplified breast cancer within one year after completion of trastuzumab-based adjuvant therapy (Press release, Puma Biotechnology, JUL 16, 2019, View Source [SID1234537547]).

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Health Canada approval was based on the Phase III ExteNET trial, a multicenter, randomized, double-blind, placebo-controlled trial of neratinib following adjuvant trastuzumab treatment. Women (n=2,840) with early stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab therapy were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year.

The results of the ExteNET trial demonstrated that after two years of follow-up, for patients with hormone receptor positive, HER2-positive early stage breast cancer patients who were treated within one year after the completion of trastuzumab based adjuvant therapy, invasive disease-free survival (iDFS) was 95.3% in the patients treated with neratinib compared with 90.8% in those receiving placebo (hazard ratio = 0.49; 95% CI: (0.30, 0.78); p=0.002).

The most common adverse reactions (>5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. The most common adverse reaction leading to discontinuation was diarrhea, which was observed in 16.8% of neratinib-treated patients. Hepatotoxicity or increases in liver transaminases led to drug discontinuation in 1.7% of neratinib-treated patients.

"Health Canada approval marks the first time Canadian women are being presented with an opportunity for extended-adjuvant therapy that will reduce the risk of disease recurrence in patients who would otherwise have had a relapse," said Jonathan Ross Goodman, Chief Executive Officer of Knight.

Puma Biotechnology’s CEO and President Alan H. Auerbach, added, "Reducing the risk of disease recurrence remains a need for patients, despite advances in the treatment of early stage HER2-positive breast cancer. We are pleased that our partner, Knight Therapeutics, will be bringing NERLYNX to patients throughout Canada. Health Canada represents the second international approval of NERLYNX this year and we are committed to supporting our partners to expand NERLYNX commercial accessibility to patients around the world."

About HER2-Positive Breast Cancer

Approximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.

On July 16, 2019 Johnson & Johnson (NYSE: JNJ) reported results for second-quarter 2019. "We delivered solid second-quarter underlying sales growth and strong earnings growth that enables us to make investments in innovation to accelerate performance in each of our businesses," said Alex Gorsky, Chairman and Chief Executive Officer. "Our pipelines continue to progress with the launch of new products and several regulatory submissions and approvals, which positions us well to deliver the next wave of transformational products and solutions. I am proud of our talented colleagues across Johnson & Johnson who continue to deliver significant healthcare advances to improve the lives of patients and consumers around the world."
SEGMENT COMMENTARY:

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Consumer
Consumer worldwide operational sales, excluding the net impact of acquisitions and divestitures, grew 2.3%* driven by NEUTROGENA, AVEENO and OGX beauty products, over-the-counter products including ZYRTEC upper respiratory and MOTRIN analgesic products, international LISTERINE mouthwash in Oral Care products and U.S. Baby Care products.

Pharmaceutical
Pharmaceutical worldwide operational sales, excluding the net impact of acquisitions and divestitures grew 4.4%* driven by DARZALEX (daratumumab), for the treatment of multiple myeloma, STELARA (ustekinumab), a biologic for the treatment of a number of immune-mediated inflammatory diseases, IMBRUVICA (ibrutinib), an oral, once-daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer, INVEGA SUSTENNA/XEPLION/INVEGA TRINZA/TREVICTA (paliperidone palmitate), long-acting, injectable atypical antipsychotics for the treatment of schizophrenia in adults, TREMFYA (guselkumab), a biologic for the treatment of adults living with moderate to severe plaque psoriasis, OPSUMIT (macitentan), an oral endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension to delay disease progression, ERLEADA (apalutamide), a next-generation androgen receptor inhibitor for the treatment of patients with non-metastatic castration-resistant prostate cancer and PREZISTA/PREZCOBIX/REZOLSTA/ SYMTUZA (D/C/F/TAF) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection, partially offset by declines in REMICADE (infliximab), a biologic approved for the treatment of a number of immune-mediated inflammatory diseases, and U.S. ZYTIGA (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer due to biosimilar and generic entrants.

Medical Devices
Worldwide Medical Devices operational sales, excluding the net impact of acquisitions and divestitures grew 3.2%* driven by the growth of electrophysiology products in the Interventional Solutions business, endocutters and international energy products in the Advanced Surgery business. As previously disclosed, the divestiture of the ASP business was completed, resulting in an approximate $2.0 billion pretax gain in the quarter.

NOTABLE NEW ANNOUNCEMENTS IN THE QUARTER:
The information contained in this section should be read in conjunction with Johnson & Johnson’s other disclosures filed with the Securities and Exchange Commission, including its Current Reports on Form 8-K, Quarterly Reports on Form 10-Q and Annual Reports on Form 10-K. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. The reader is also encouraged to review all other news releases available online in the Investors section of the company’s website at news releases.

Pipeline Updates
Regulatory Approvals
IMBRUVICA (ibrutinib) – CHMP Positive Opinions in combination with obinutuzumab in CLL and in combination with rituximab in WM
(press release)
DARZALEX (daratumumab) – Newly diagnosed patients with Multiple Myeloma in combination with Lenalidomide and Dexamethasone (U.S.)
(press release)
Regulatory Submissions
DARZALEX (daratumumab) – Subcutaneous formulation in multiple myeloma (U.S.)1

(press release)
ERLEADA (apalutamide) – Metastatic Hormone-Sensitive Prostate Cancer (EU)
(press release)
ERLEADA (apalutamide) – Metastatic Castration – Sensitive Prostate Cancer (U.S)
(press release)
Rilpivirine and Cabotegravir – Monthly, Injectable, Two-Drug Regimen for Treatment of HIV
(press release)

1 Subsequent to the quarter

FULL YEAR 2019 GUIDANCE:

Johnson & Johnson does not provide GAAP financial measures on a forward-looking basis because the company is unable to predict with reasonable certainty the ultimate outcome of legal proceedings, unusual gains and losses, acquisition-related expenses and purchase accounting fair value adjustments without unreasonable effort. These items are uncertain, depend on various factors, and could be material to Johnson & Johnson’s results computed in accordance with GAAP.

Other modeling considerations will be provided on the webcast.

WEBCAST INFORMATION:
Johnson & Johnson will conduct a conference call with investors to discuss this earnings release today at 8:30 a.m., Eastern Time. A simultaneous webcast of the call for investors and other interested parties may be accessed by visiting the Johnson & Johnson website. A replay and podcast will be available approximately two hours after the live webcast in the Investors section of the company’s website at events-and-presentations.

On July 16, 2019 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seattle Genetics, Inc. (Nasdaq:SGEN) reported submission of a Biologics License Application for accelerated approval to the U.S. Food and Drug Administration for the investigational agent enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer who have received a PD-1/L1 inhibitor and who have received a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting (Press release, Astellas, JUL 16, 2019, View Source [SID1234537545]).

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The submission is based on results from the first cohort of patients in the EV-201 pivotal phase 2 clinical trial that were presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June. Enfortumab vedotin is an investigational antibody-drug conjugate (ADC) that targets Nectin-4, a protein that is highly expressed in urothelial cancers.i

"There are limited treatment options for patients with advanced urothelial cancer, and we are encouraged by the results observed in the pivotal trial for enfortumab vedotin," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head at Astellas.

"There is an urgent need for new therapies for patients with advanced urothelial cancer, and we look forward to working with our partner Astellas and the FDA on the review of this application," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics.

Based on preliminary results from a phase 1 trial (EV-101), the FDA granted enfortumab vedotin Breakthrough Therapy designation for patients with locally advanced or metastatic urothelial cancer whose disease has progressed during or following checkpoint inhibitor therapy.

A global, randomized phase 3 confirmatory clinical trial (EV-301) is ongoing and is intended to support global registrations. Another ongoing trial, EV-103, is evaluating enfortumab vedotin in earlier lines of treatment for patients with locally advanced or metastatic urothelial cancer, including in combination with pembrolizumab and/or platinum chemotherapy in newly diagnosed patients as well as patients whose cancer progressed from earlier-stage disease.

About the EV-201 Trial

EV-201 is an ongoing single-arm, pivotal phase 2 clinical trial of enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy or who are ineligible for cisplatin (cohort 2). In cohort 1, 128 patients were enrolled at multiple centers internationally.ii The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability. EV-201 continues to enroll patients in cohort 2.

More information about enfortumab vedotin clinical trials can be found at clinical trials.gov.

About Urothelial Cancer

Urothelial cancer is the most common type of bladder cancer (90 percent of cases).iii In 2018, more than 82,000 people were diagnosed with bladder cancer in the United States. Globally, approximately 549,000 people were diagnosed with bladder cancer last year, and there were approximately 200,000 deaths worldwide.iv

About Enfortumab Vedotin

Enfortumab vedotin is an investigational ADC composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE, using Seattle Genetics’ proprietary linker technology. Enfortumab vedotin targets Nectin-4, a cell adhesion molecule that is expressed on many solid tumors, and that has been identified as an ADC target by Astellas.

The safety and efficacy of enfortumab vedotin are under investigation and have not been established. There is no guarantee that the agent will receive regulatory approval or become commercially available for the uses being investigated.

On July 16, 2019 Aptose Biosciences Inc. (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that dosing of CG-806, the company’s highly potent, first-in-class pan-FLT3/pan-BTK inhibitor, has commenced its Phase 1a/b dose-escalation study in patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) or non-Hodgkin lymphomas (NHL) who have failed or are intolerant to standard therapies (Press release, Aptose Biosciences, JUL 16, 2019, View Source [SID1234537544]). In parallel, the company has successfully completed the first two dose levels of the Phase 1b clinical trial of MYC inhibitor APTO-253, and is now dosing the third dose cohort. Initial data from the first two cohorts demonstrate MYC inhibition in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

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"We are pleased to announce that the much anticipated first-in-human dosing with CG-806 has occured, and that we have successfully initiated oral dosing of CG-806 in a patient with CLL," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "CG-806 is a highly potent non-covalent inhibitor of all forms of BTK and FLT3 driver kinases that simultaneously suppresses multiple oncogenic signaling pathways upon which cancer cells rely for survival, yet with a precision that avoids targets typically associated with toxicity. Separately," continued Dr. Rice, "we completed dosing of the first two cohorts in a Phase 1b trial with our APTO-253 MYC inhibitor, with only one patient required in each cohort. Both patients completed the 28-day cycle and experienced reductions of MYC gene expression in their peripheral blood cells, an important finding as MYC plays a central role in the oncogenic process. In addition, the third dose cohort at 66mg/m2 is enrolling efficiently for a total of three planned patients. We are hopeful that both CG-806 and APTO-253 will provide benefit to those patients with devastating hematologic malignancies who have failed standard therapies. We are eager to treat additional patients in the coming months and look forward to reporting results later this year."

About the CG-806 Clinical Trial

The Phase 1a/b multicenter, open-label, dose-escalation clinical trial of CG-806 is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamic responses, and preliminary efficacy of CG-806, and establish the recommended Phase 2 dose. Aptose is conducting the Phase 1 trial with orally administered CG-806 in ascending doses to patients with relapsed or refractory B cell malignancies, including CLL/SLL and NHL, until the maximum tolerated dose or recommended dose that is most efficacious and safe is reached. Seven U.S. sites are currently open for screening and enrolling patients for the study. More clinical sites are planned to open for enrollment in the near future. More information is available at www.clinicaltrials.gov (here). Pending collection and careful review of the initial safety data and predictive pharmacokinetic data in humans from the Phase 1 dose escalation trial in patients with B-cell cancers, Aptose plans to seek allowance from the FDA to move into patient populations that include relapsed or refractory AML and MDS in a separate Phase 1 trial.

About CG-806

CG-806 is an oral, first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor and is in a Phase 1 clinical trial for the treatment of hematologic malignancies. This small molecule, in-licensed from CrystalGenomics Inc. in Seoul, South Korea, demonstrates potent inhibition of wild type and all mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), cures animals of AML in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML and other hematologic malignancies. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser (C481S) mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL/SLL, FL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent or other non-covalent BTK inhibitors. Because CG-806 targets key kinases/pathways operative in malignancies derived from the bone marrow, it is in development for B-cell cancers and AML.

About APTO-253 and the APTO-253 Clinical Trial

The Phase 1b, multicenter, open-label dose-escalation clinical trial of APTO-253 is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamic responses and establish the recommended Phase 2 dose and efficacy of APTO-253 as a single agent. APTO-253 is being administered once weekly, over a 28-day cycle. The study is expected to enroll up to 20 patients with relapsed or refractory acute myeloid leukemia (AML) and high-risk MDS patients. The study is designed to then transition, as appropriate, to single-agent expansion cohorts in AML and MDS, followed by combination studies. More information can be found at www.clinicaltrials.gov (here). APTO-253 is a small molecule, targeted therapeutic agent that inhibits expression of the MYC oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells. The MYC oncogene is overexpressed in hematologic cancers, including AML. Aptose researchers have reported the ability of APTO-253 to induce cell death, or apoptosis, in multiple blood cancer cell lines including AML, as well as in vitro synergy with various classes of conventional approved and investigational therapies for AML or MDS, but without causing toxicity to the normal bone marrow functions.

On July 16, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that worldwide net sales of DARZALEX (daratumumab) as reported by Johnson & Johnson were USD 774 million in the second quarter of 2019 compared to USD 511 million in the second quarter of 2018, an increase of approximately 51% (Press release, Genmab, JUL 16, 2019, View Source [SID1234537543]). The 2019 second quarter net sales were USD 369 million in the U.S. and USD 405 million in the rest of the world.

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Johnson & Johnson reported worldwide operational DARZALEX sales growth (excluding impact of foreign currency movements) between the two second quarter periods in 2018 and 2019, respectively, of approximately 57%. According to Johnson & Johnson, sales in the second quarter of 2019 included a one-time adjustment outside the U.S. related to the completion of pricing and reimbursement discussions in certain European countries, which positively impacted this worldwide operational growth by 16 percentage points.

Genmab will receive royalties on the worldwide net sales of DARZALEX under the exclusive worldwide license to Janssen Biotech, Inc. to develop, manufacture and commercialize DARZALEX.

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United Stated, Europe and Japan.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).1,2,3,4,5

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis, NKT-cell lymphoma and B-cell and T-cell ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.