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Cerulean Receives FDA Fast Track Designation for CRLX101 for the Treatment of Platinum-Resistant Ovarian Cancer

On July 19, 2016 Cerulean Pharma Inc. (NASDAQ:CERU), a clinical-stage company developing nanoparticle-drug conjugates (NDCs), reported that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for Cerulean’s lead nanoparticle-drug conjugate, CRLX101, in combination with paclitaxel, for the treatment of platinum-resistant ovarian carcinoma, fallopian tube or primary peritoneal cancer (Press release, Cerulean Pharma, JUL 19, 2016, View Source [SID:1234513963]).

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"We appreciate the FDA’s acknowledgement of CRLX101’s potential in an area of significant unmet medical need," said Christopher D. T. Guiffre, President and Chief Executive Officer of Cerulean. "We are encouraged by the profound treatment effect observed early in the ongoing clinical trial with the GOG Foundation, Inc. (GOG), and we look forward to working closely with the FDA as we endeavor to bring a new treatment option to women living with platinum-resistant ovarian cancer."

CRLX101 is being evaluated in combination with weekly paclitaxel for the treatment of recurrent platinum-resistant ovarian carcinoma in a Phase 1b/2 clinical trial. Data from the Phase 1b portion of the trial were the subject of an oral presentation at the Gynecologic Oncology 2016 Conference in May. These data showed that five of the first nine patients (56%) enrolled in the trial achieved partial responses. Of note, five of the nine patients enrolled in the Phase 1b trial previously failed Avastin (bevacizumab) and three of these five patients achieved partial responses. Cerulean is conducting this trial in collaboration with the GOG and expects to provide an update at the European Society for Medical Oncology 2016 Congress.

In 2015, CRLX101 was granted Orphan Drug designation for the treatment of ovarian cancer.

The FDA’s Fast Track Program is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious conditions and that demonstrate the potential to address unmet medical needs. Drugs that receive this designation benefit from more frequent communications and meetings with FDA to review the drug’s development plan, including the design of the proposed clinical trials and the extent of data needed for approval.

About CRLX101

CRLX101 is a nanoparticle-drug conjugate (NDC) designed to concentrate in tumors and slowly release its anti-cancer payload, camptothecin, inside tumor cells. CRLX101 inhibits topoisomerase 1 (topo 1), which is involved in cellular replication, and also inhibits hypoxia-inducible factor-1α (HIF-1α), which research suggests is a master regulator of cancer cell survival mechanisms. CRLX101 has shown activity in four different tumor types, both as monotherapy and in combination with other cancer treatments. CRLX101 is in Phase 2 clinical development and has been dosed in more than 350 patients. The U.S. FDA has granted CRLX101 Orphan Drug designation for the treatment of ovarian cancer, Fast Track designation in combination with paclitaxel for platinum-resistant ovarian carcinoma, fallopian tube or primary peritoneal cancer, and Fast Track designation in combination with Avastin in metastatic renal cell carcinoma.

Arbutus Reports Topline Results from TKM-PLK1 HCC Clinical Trial

On July 19, 2016 Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading hepatitis B virus (HBV) therapeutic solutions company, reported topline results from the completed Phase I/II TKM-PLK1 clinical study in patients with advanced Hepatocellular Carcinoma (HCC). Arbutus intends to explore partnership opportunities to enable further study of TKM-PLK-1 in HCC (Press release, Arbutus Biopharma, JUL 19, 2016, View Source [SID:1234513962]).

Arbutus today reported the following topline results from the Phase I/II study of TKM-PLK1 in HCC:

TKM-PLK1 was well-tolerated at all dose levels;
51% of subjects showed overall stable disease (SD) according to RECIST criteria;
22% of subjects showed an overall partial response (PR) according to Choi response criteria;
Tumor density reduction of up to 59% was observed;
"We are encouraged by the results from the TKM-PLK1 clinical trial in HCC patients and believe it supports further evaluation of this candidate as a potential treatment for HCC," said Dr. Mark Kowalski, Arbutus’ Chief Medical Officer. "The observed radiographic tumor density changes are consistent with tumor necrosis in a significant proportion of subjects, warranting further study of TKM-PLK1 for HCC, alone and in combination with other therapies."

"We are very pleased to report the positive results of this study of TKM-PLK1 in HCC, which we view as further validation of our capability to develop promising product candidates using our proprietary LNP delivery technology," said Dr. Mark J. Murray, Arbutus’ President and CEO. "Given Arbutus’ focus on HBV, we look forward to finding the right partner to advance the development of TKM-PLK1 for HCC and maximize the value of this asset for our shareholders."

Trial Design
The Phase I/II TKM-PLK1 HCC clinical study was an open-label, multi-center, study in patients with advanced HCC conducted in the US, Asia, and Canada. The trial was designed to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of the product. TKM-PLK1 was administered weekly with each four-week cycle consisting of three once-weekly doses followed by a rest week. The study included a total of 43 subjects (12 subjects in the dose escalation arm, followed by 31 subjects in the expansion cohort). The HCC efficacy endpoint of the study was tumor response rate.

About TKM-PLK1
TKM-PLK1 (TKM-080301) is a lipid nanoparticle (LNP) encapsulated small interfering RNA (siRNA) directed against polo-like kinase 1 (PLK1), a protein involved in tumor cell proliferation and a validated oncology target. Inhibition of PLK1 expression prevents the tumor cell from completing cell division, resulting in cell cycle arrest and death of the cancer cell. TKM-PLK1 has been evaluated in clinical trials with patients who have HCC, gastrointestinal neuroendocrine tumors (GI-NET), and adrenocortical carcinoma (ACC).

Onconova Announces Enrollment of First Patient in Japan by SymBio

On July 19, 2016 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the enrollment of the first patient in Japan by SymBio Pharmaceuticals in the global Phase 3 INSPIRE trial, investigating IV rigosertib as a treatment for higher-risk (HR) myelodysplastic syndromes (MDS) following failure of hypomethylating agent (HMA) therapy (Press release, Onconova, JUL 19, 2016, View Source [SID:1234513960]). SymBio licensed rights to rigosertib from Onconova for Japan and Korea in 2011 and has completed two Phase 1 trials in Japan.

The INSPIRE pivotal trial is now open for patient enrollment in more than 90 sites in the U.S., Europe, Canada, Australia, Israel and Japan. The first patient in this trial was enrolled in December 2015, and so far, patients have been enrolled in six countries on four continents.

"We are pleased to be participating in the Phase 3 INSPIRE trial for HR-MDS patients," said Fuminori Yoshida, President and CEO of SymBio. "The enrollment of the first patient in Japan for this pivotal Phase 3 trial marks an important milestone for SymBio. We believe that rigosertib has the potential to address important unmet medical needs of MDS patients in Japan. As such, beyond our participation in this study, we have also completed two Phase 1 studies and are now preparing to enroll patients in a Japanese Phase 1 trial of oral rigosertib plus azacitidine in patients with MDS."

"The initiation of the Phase 3 INSPIRE trial in Japan represents an important achievement in our collaboration with SymBio," commented Ramesh Kumar, Ph.D., President and CEO of Onconova. "In addition to participating in this trial, SymBio is also playing a key role in Japan in the development of single-agent oral rigosertib and oral rigosertib in combination with azacitidine. We look forward to providing periodic updates on the progress of the INSPIRE trial and publications and scientific presentations related to rigosertib."

The INSPIRE trial is a multi-center, randomized controlled Phase 3 study to assess the efficacy and safety of IV rigosertib in HR-MDS patients who had progressed on, failed to respond to, or relapsed, following previous treatment with HMAs. The trial will enroll approximately 225 patients randomized at a 2:1 ratio into two treatment arms: IV rigosertib plus Best Supportive Care versus Physician’s Choice plus Best Supportive Care. It is anticipated that more than 130 sites across four continents (North America, Europe, Australia and Asia) will participate in this trial. The primary endpoint of INSPIRE is overall survival and an interim analysis is anticipated.

About INSPIRE

The INternational Study of Phase III IV RigosErtib, or INSPIRE, is based on guidance received from the U.S. Food and Drug Administration and European Medicines Agency and derives from the findings of the ONTIME Phase 3 trial. INSPIRE is a multi-center, randomized controlled study to assess the efficacy and safety of IV rigosertib in HR-MDS patients who had progressed on, failed to respond to, or relapsed after previous treatment with an HMA within the first nine months of initiation of HMA treatment. This time frame optimizes the opportunity to respond to treatment with an HMA prior to declaring treatment failure, as per NCCN Guidelines.1 The trial will enroll approximately 225 patients randomized at a 2:1 ratio into two treatment arms: IV rigosertib plus Best Supportive Care versus Physician’s Choice plus Best Supportive Care. The primary endpoint of INSPIRE is overall survival and an interim analysis is anticipated. Full details of the INSPIRE trial, such as inclusion and exclusion criteria, as well as secondary endpoints, can be found on clinicaltrials.gov (NCT02562443).

About Rigosertib

Rigosertib is a small molecule inhibitor of cellular signaling and acts as a Ras mimetic. These effects of rigosertib appear to be mediated by direct binding of the compound to the Ras-binding domain (RBD) found in many Ras effector proteins, including the Raf kinases and PI3K. The therapeutic focus for rigosertib is myelodysplastic syndromes (MDS), a group of bone marrow disorders characterized by ineffective formation of blood cells that often converts into acute myeloid leukemia (AML). Clinical trials for rigosertib are being conducted at leading institutions in the U.S., Europe, and the Asia-Pacific region. Both the Intravenous (IV) and oral formulations of rigosertib are being tested in multiple clinical trials. Rigosertib is protected by issued patents (earliest expiry in 2026) and has been awarded Orphan Designation for MDS in the U.S., Europe and Japan.

ZIOPHARM Provides Update Regarding Phase I Study of Gene Therapy Candidate Ad-RTS-hIL-12 in Brain Cancer

On July 19, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) reported an update regarding the Company’s ongoing multicenter Phase I study of Ad-RTS-hIL-12 + orally administered veledimex in recurrent or progressive glioblastoma (GBM) or grade III malignant glioma (Press release, Ziopharm, JUL 19, 2016, View Source [SID:1234513956]).

The patient death resulting from intracranial hemorrhage in the third cohort of this Phase I study was deemed unrelated to study drug following the receipt and analysis of additional information by the sponsor and the study’s Safety Review Committee. As with all study events, the Company expects to report the data to the U.S. Food and Drug Administration in accordance with the study’s protocol and applicable regulations. As previously announced, the study remains open for enrollment. The Company expects to provide further updates on the progress of the study, including longer-term survival follow up, at an appropriate meeting later this year.

"Recurrent GBM is a devastating disease with an expected overall survival that remains far too short as this case illustrates," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "Preliminary overall survival in this study, including a median follow-up of over 8 months in the first dose cohort, remain encouraging, and we will continue to work diligently toward understanding the full potential of Ad-RTS-hIL-12 + veledimex in this disease, with the goal of providing safe and effective treatment options to these patients."

About Glioblastoma

Glioblastoma is an aggressive primary brain tumor affecting approximately 74,000 people worldwide each year.i, ii Recurrent glioblastoma is an aggressive cancer with one of the lowest 3-year survival rates, at 3%, among all cancers.iii For patients who have experienced multiple recurrences the prognosis is particularly poor, with a median overall survival (OS) of 6-7 months, while OS in patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy, is approximately 3-5 months.iv, v

Johnson & Johnson Reports 2016 Second-Quarter Results:

On July 19, 2016 Johnson & Johnson (NYSE: JNJ) reported sales of $18.5 billion for the second quarter of 2016, an increase of 3.9% as compared to the second quarter of 2015 (Press release, Johnson & Johnson, JUL 19, 2016, View Source [SID:1234513959]).

Operational sales results increased 5.3% and the negative impact of currency was 1.4%. Domestic sales increased 7.4%. International sales increased 0.4%, reflecting operational growth of 3.1% and a negative currency impact of 2.7%. Excluding the net impact of acquisitions, divestitures and hepatitis C sales, on an operational basis, worldwide sales increased 7.9%, domestic sales increased 8.8% and international sales increased 6.9%.* Operations in Venezuela negatively impacted worldwide operational sales growth by 30 basis points, and international sales growth by 70 basis points.

Net earnings and diluted earnings per share for the second quarter of 2016 were $4.0 billion and $1.43, respectively. Second quarter 2016 net earnings included after-tax intangible amortization expense of approximately $0.2 billion and a charge for after-tax special items of approximately $0.7 billion. Second quarter 2015 net earnings included after-tax intangible amortization expense of approximately $0.2 billion and a charge for after-tax special items of approximately $0.1 billion. Excluding after-tax intangible amortization expense and special items, adjusted net earnings for the current quarter were $4.9 billion and adjusted diluted earnings per share were $1.74, representing increases of 1.1% and 1.8%, respectively, as compared to the same period in 2015. * On an operational basis, adjusted diluted earnings per share also increased 1.8%.* A reconciliation of non-GAAP financial measures is included as an accompanying schedule.

“We continue to see good momentum through the first half of 2016, delivering solid results in the second quarter, supported by strong underlying growth across our enterprise,” said Alex Gorsky, Chairman and Chief Executive Officer. “We saw notable strength in our Pharmaceuticals business due to the continued success of new products, and also achieved significant clinical milestones, advancing our robust pipeline. In our Consumer business, we are executing strategic portfolio decisions to expand our market leadership in key segments, and in Medical Devices, we are continuing to accelerate our growth driven by new product launches and transforming our commercial models.”

Mr. Gorsky continued, “I am proud of our dedicated and talented employees whose commitment to advancing health and well-being for patients and consumers around the world is fueling our growth.”

The Company increased its sales guidance for the full-year 2016 to $71.5 billion to $72.2 billion. Additionally, the Company increased its adjusted earnings guidance for full-year 2016 to $6.63 – $6.73 per share.*

Worldwide Consumer sales of $3.4 billion for the second quarter 2016 represented a decrease of 1.8% versus the prior year, consisting of an operational increase of 1.5% and a negative impact from currency of 3.3%. Domestic sales increased 2.1%; international sales decreased 4.4%, which reflected an operational increase of 1.0% and a negative currency impact of 5.4%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 3.9%, domestic sales increased 6.8% and international sales increased 2.0%*. Operations in Venezuela negatively impacted worldwide Consumer operational sales growth by 120 basis points, and international sales growth by 200 basis points.

Primary contributors to Consumer operational sales results were NEUTROGENA and AVEENO skin care products; over-the-counter products, including TYLENOL and MOTRIN analgesics, digestive health products and international anti-smoking aids; and LISTERINE oral care products.

During the quarter, the acquisitions of NeoStrata Company, Inc., a global leader in dermocosmetics, and the HIPOGLÓS diaper rash cream brand in Brazil were completed. In addition, subsequent to the quarter, the acquisition of Vogue International LLC, a privately-held company focused on the marketing, development and distribution of salon-influenced and nature inspired hair care and other personal care products, was completed for $3.3 billion in cash.

Worldwide Pharmaceutical sales of $8.7 billion for the second quarter 2016 represented an increase of 8.9% versus the prior year with an operational increase of 9.7% and a negative impact from currency of 0.8%. Domestic sales increased 13.2%; international sales increased 3.1%, which reflected an operational increase of 4.9% and a negative currency impact of 1.8%. Excluding the net impact of acquisitions, divestitures and hepatitis C sales, on an operational basis, worldwide sales increased 12.8%, domestic sales increased 13.9% and international sales increased 11.2%.*

Worldwide operational sales growth was driven by new products and the strength of core products. Strong growth in new products include IMBRUVICA (ibrutinib), an oral, once-daily therapy approved for use in treating certain B-cell malignancies, a type of blood or lymph node cancer; XARELTO (rivaroxaban), an oral anticoagulant; DARZALEX (daratumumab), for the treatment of patients with multiple myeloma; INVOKANA/INVOKAMET (canagliflozin), for the treatment of adults with type 2 diabetes; and ZYTIGA (abiraterone acetate), an oral, once-daily medication for use in combination with prednisone for the treatment of metastatic, castration-resistant prostate cancer. New product sales growth was negatively impacted by lower sales of OLYSIO/SOVRIAD (simeprevir) due to competitive entrants.

Additional contributors to operational sales growth include STELARA (ustekinumab), a biologic approved for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis; SIMPONI/SIMPONI ARIA (golimumab) and REMICADE (infliximab), biologics approved for the treatment of a number of immune-mediated inflammatory diseases; and INVEGA SUSTENNA/XEPLION/TRINZA (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 INVOKAMET (canagliflozin/metformin HCl) for first-line treatment of adults with type 2 diabetes and an expanded label for IMBRUVICA (ibrutinib) to include overall survival and combination data in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The European Commission (EC) granted conditional approval to DARZALEX (daratumumab) for monotherapy of adult patients with relapsed and refractory multiple myeloma and also approved IMBRUVICA (ibrutinib) for the treatment of adult patients with previously untreated chronic lymphocytic leukemia, TREVICTA (paliperidone palmitate a 3 monthly injection) for the maintenance treatment of schizophrenia in adult patients, and SIMPONI (golimumab) for the treatment of polyarticular juvenile idiopathic arthritis.

In addition, the divestiture of the company’s controlled substance raw material and active pharmaceutical ingredient business to SK Capital Partners, a private equity company, was completed.

Worldwide Medical Devices sales of $6.4 billion for the second quarter 2016 represented an increase of 0.8% versus the prior year consisting of an operational increase of 1.8% and a negative currency impact of 1.0%. Domestic sales increased 1.0%; international sales increased 0.6%, which reflected an operational increase of 2.6% and a negative currency impact of 2.0%. Excluding the net impact of acquisitions and divestitures, on an operational basis, worldwide sales increased 3.9%, domestic sales increased 1.9% and international sales increased 5.8%.* Operations in Venezuela negatively impacted worldwide operational sales growth by 30 basis points, and international sales growth by 50 basis points.

Primary contributors to operational sales growth were endocutters, energy and biosurgical products in the Advanced Surgery business; electrophysiology products in the Cardiovascular business; joint reconstruction and U.S. trauma products in the Orthopaedics business; and ACUVUE contact lenses in the Vision Care business.

During the quarter, the acquisition of privately-held BioMedical Enterprises, Inc., a leading manufacturer of Nitinol orthopaedic implants for small bone fixation, was completed.