CMS Establishes Unique J-Code for BENDEKA® (bendamustine hydrochloride) Injection

On November 2, 2016 Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) and Eagle Pharmaceuticals, Inc. (Nasdaq: EGRX) reported that the Centers for Medicare & Medicaid Services (CMS) has established a unique, product-specific billing code, or J-code (J9034), for BENDEKA (bendamustine hydrochloride) Injection (Press release, Eagle Pharmaceuticals, NOV 2, 2016, View Source [SID1234516173]. The J-code will become effective on January 1, 2017).

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The new J-code provides reimbursement coding clarity to outpatient facilities and physicians that administer BENDEKA, facilitating access for patients and Medicare, Medicaid and commercial insurance reimbursement.

"We are pleased that CMS recognized that the unique formulation and delivery mechanism offered by BENDEKA required separate recognition from other bendamustine products currently on the market. We expect the new J-code will provide greater access for patients, facilitate reimbursement and enable greater adoption of BENDEKA in the market," said Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals.

"This is an important milestone for Teva as we continue to advance our bendamustine franchise with BENDEKA," said Paul Rittman, Senior Vice President and General Manager, Teva Oncology. "We are committed to serving patients in need of this important therapy and are pleased that a unique J-code has been established to assist providers in obtaining reimbursement for BENDEKA."

BENDEKA, a liquid, low-volume (50 mL) and short-time (10-minute) infusion formulation of bendamustine hydrochloride, was approved by the U.S. Food and Drug Administration (FDA) in December 2015 for the treatment of patients with chronic lymphocytic leukemia (CLL) and for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Efficacy in CLL relative to first-line therapies other than chlorambucil has not been established.

Under a February 2015 exclusive license agreement for BENDEKA, Teva Pharmaceutical Industries, Ltd. is responsible for all U.S. commercial activities for the product including promotion and distribution. BENDEKA was launched by Teva in late January 2016 and now is the most used bendamustine product. Please see Important Safety Information below including contraindication in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine, polyethylene glycol 400, propylene glycol, or monothioglycerol.

Indications

BENDEKA is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). Efficacy relative to first-line therapies other than chlorambucil has not been established.

BENDEKA is indicated for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

Important Safety Information

Contraindication: BENDEKA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine, polyethylene glycol 400, propylene glycol, or monothioglycerol.

Myelosuppression: Bendamustine hydrochloride caused severe myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies. Three patients (2%) died from myelosuppression-related adverse reactions. Monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle.

Infections: Infection, including pneumonia, sepsis, septic shock, hepatitis and death has occurred. Patients with myelosuppression following treatment with BENDEKA are more susceptible to infections. Patients treated with Bendamustine hydrochloride are at risk for reactivation of infections including (but not limited to) hepatitis B, cytomegalovirus, Mycobacterium tuberculosis, and herpes zoster. Patients should undergo appropriate monitoring, prophylaxis, and treatment measures.

Anaphylaxis and Infusion Reactions: Infusion reactions to bendamustine hydrochloride have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus, and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe (Grade 3-4) reactions. Ask patients about symptoms suggestive of infusion reactions after their first cycle of therapy. Consider measures to prevent severe reactions, including antihistamines, antipyretics, and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion reactions.

Tumor Lysis Syndrome: Tumor lysis syndrome associated with bendamustine hydrochloride has occurred. The onset tends to be within the first treatment cycle with –bendamustine hydrochloride and, without intervention, may lead to acute renal failure and death. Preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels. There may be an increased risk of severe skin toxicity when bendamustine hydrochloride and allopurinol are administered concomitantly.

Skin Reactions: Skin reactions have been reported with bendamustine hydrochloride treatment including rash, toxic skin reactions, and bullous exanthema. In a study of bendamustine hydrochloride (90 mg/m2) in combination with rituximab, one case of toxic epidermal necrolysis (TEN) occurred. TEN has been reported for rituximab. Cases of Stevens-Johnson syndrome (SJS) and TEN, some fatal, have been reported when bendamustine hydrochloride was administered concomitantly with allopurinol and other medications known to cause these syndromes. Where skin reactions occur, they may be progressive and increase in severity with further treatment. Monitor patients with skin reactions closely. If skin reactions are severe or progressive, withhold or discontinue BENDEKA.

Other Malignancies: There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with bendamustine hydrochloride, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia, and bronchial carcinoma. The association with BENDEKA therapy has not been determined.

Extravasation Injury: Extravasations resulting in hospitalizations from erythema, marked swelling, and pain have been reported with bendamustine hydrochloride. Assure good venous access prior to starting drug infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of BENDEKA.

Embryo-fetal Toxicity: Bendamustine hydrochloride can cause fetal harm when administered to a pregnant woman. Women should be advised to avoid becoming pregnant while using BENDEKA.

Most Common Adverse Reactions:

• Adverse reactions (frequency >5%) during infusion and within 24 hours post-infusion are nausea and fatigue.

• Most common non-hematologic adverse reactions for CLL (frequency ≥15%) are pyrexia, nausea, and vomiting.

• Most common non-hematologic adverse reactions for NHL (frequency ≥15%) are nausea, fatigue, vomiting, diarrhea, pyrexia, constipation, anorexia, cough, headache, weight decreased, dyspnea, rash, and stomatitis.

• Most common hematologic abnormalities (frequency ≥15%) are lymphopenia, anemia, leukopenia, thrombocytopenia, and neutropenia.

For BENDEKA Full Prescribing Information, please visit: View Source

Aduro Biotech Reports Third Quarter 2016 Financial Results

On November 2, 2016 Aduro Biotech, Inc. (NASDAQ:ADRO) reported financial results for the third quarter 2016 (Press release, Aduro BioTech, NOV 2, 2016, View Source;p=RssLanding&cat=news&id=2218713 [SID1234516171]). Net loss for the three months ended September 30, 2016 was $35.1 million, or $0.54 per share, and for the nine months ended September 30, 2016 net loss was $61.6 million, or $0.96 per share, compared to a net income of $0.6 million, or $0.01 per share, and net loss of $42.3 million, or $1.09 per share respectively, for the same periods in 2015.

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Cash, cash equivalents and marketable securities totaled $387.1 million at September 30, 2016, compared to $431.0 million at December 31, 2015.

Third Quarter 2016 Financial Results

Revenue for the quarter and nine months ended September 30, 2016 was $3.8 million and $46.8 million, respectively, compared to $19.1 million and $38.6 million, for the same periods in 2015. The decrease in the third quarter of 2016 was primarily related to the full recognition of the Janssen upfront license fee in 2015. The increase for the nine months ended September 30, 2016 was primarily due to the receipt of a $35.0 million milestone payment from Novartis.

Research and development expenses for the quarter and nine months ended September 30, 2016 were $19.0 million and $66.9 million, respectively, compared to $11.8 million and $36.0 million for the same periods in 2015. The increase for the quarter was primarily due to licensing fees related to our STING technology platform and additional personnel-related costs which include stock-based compensation, partially offset by declines in contract manufacturing and clinical trial expenses for our pancreatic cancer program. The increase for the nine month period was primarily due to GVAX pancreas manufacturing expenses during the first half of 2016, and to a lesser extent due to additional personnel-related costs, contract research expenses, and licensing fees.

General and administrative expenses for the quarter and nine months ended September 30, 2016 were $8.6 million and $26.3 million, respectively, compared to $6.9 million and $19.0 million for the same periods in 2015. The increases in both periods were primarily due to additional personnel-related costs, including stock-based compensation, and the expansion of our office and laboratory facilities.

There was no loss from remeasurement of fair value of warrants during the quarter or nine months ended September 30, 2016 or for the third quarter of 2015. The $26.1 million loss from remeasurement of fair value of warrants for the nine months ended September 30, 2015 occurred in April 2015 when certain outstanding warrants were no longer subject to future remeasurement.

Provision for income taxes for the quarter and nine months ended September 30, 2016 was $11.7 million and $16.4 million, respectively. There was no provision for income taxes for the comparable periods in 2015. The income tax expense recorded for the quarter and nine months ended September 30, 2016 was primarily related to current and deferred federal income taxes.

Provectus Biopharmaceuticals Announces Data on PV-10 for Treatment of Pancreatic Cancer Scheduled for Poster Presentation at 31st SITC Annual Meeting

On November 2, 2016 Provectus Biopharmaceuticals, Inc. (OTCQB:PVCT, www.provectusbio.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus" or "The Company"), reported that researchers will present data on the treatment of pancreatic cancer with PV-10, an investigational ablative immunotherapy under development by Provectus for solid tumor cancers, at the 31st Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Provectus Pharmaceuticals, NOV 2, 2016, View Source [SID1234516169]).

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The poster, "Intralesional injection with rose bengal and systemic chemotherapy induces anti-tumor immunity in a murine model of pancreatic cancer," will detail research undertaken at Moffitt Cancer Center by a team of scientists led by Shari Pilon-Thomas.

Dr. Pilon-Thomas has informed Provectus that she will be present Saturday, November 12 at both the SITC (Free SITC Whitepaper) luncheon from 11:45 a.m. to 1:00 p.m. as well as the Poster Reception from 6:45 to 8:00 p.m.

The poster presentation is number 264. The full abstract will be available on line at SITC (Free SITC Whitepaper)ancer.org on November 8 according to conference organizers.

The 31st SITC (Free SITC Whitepaper) Annual Meeting and Associated Programs will be held November 9-13 at the Gaylord National Hotel & Convention Center in National Harbor, Maryland.

TRILLIUM THERAPEUTICS ADVANCES TTI-621 INTO PHASE 1B COHORT EXPANSION ENROLLMENT

On November 2, 2016 Trillium Therapeutics Inc. (NASDAQ: TRIL; TSX: TR), a clinical-stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported that it has advanced its novel investigational drug TTI-621, a SIRPa-IgG1 Fc fusion protein, from dose escalation into Phase 1b cohort expansion enrollment in patients with advanced hematologic malignancies (Filing, 6-K, Trillium Therapeutics, NOV 2, 2016, View Source [SID1234516179]). As part of the advancement, the company provides the following study updates:

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Trillium has completed a dose-escalation phase of TTI-621 in patients with lymphoma, and will report interim Phase 1a data at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December.

Patient enrollment across a broad spectrum of hematologic malignancies has commenced in the Phase 1b multi-cohort expansion portion of the trial. The trial’s objectives are to further characterize the safety of TTI-621 and gain preliminary evidence of anti-tumor activity in patients with a variety of hematologic malignancies.

In addition to the eight original expansion cohorts, indolent B cell lymphoma, aggressive B cell lymphoma, T cell lymphoma, Hodgkin lymphoma, chronic lymphocytic leukemia, multiple myeloma, acute myeloid leukemia and myelodysplastic syndrome, the phase 1b expansion will also include patients with myeloproliferative neoplasms.

In a separate expansion cohort, patients with CD20-positive lymphomas will be treated with TTI-621 in combination with rituximab.

The Phase 1b enrollment will engage multiple new clinical trial sites, in addition to the existing five participating in Phase 1a.
"TTI-621 is a decoy receptor that blocks CD47 — a ‘do not eat’ signal that is a key regulator of innate and adaptive immunity," commented Trillium’s Chief Medical Officer, Eric Sievers, MD. "Having established a well-tolerated dose and schedule of TTI-621, we are enthusiastic to characterize safety and anti-tumor activity across multiple blood cancers. In addition, we look forward to evaluating TTI-621 in combination with rituximab."

Verastem Licenses Duvelisib from Infinity Pharmaceuticals

On November 2, 2016 Verastem, Inc. (NASDAQ:VSTM) and Infinity Pharmaceuticals, Inc. (NASDAQ:INFI), reported that the companies entered into a license agreement under which Verastem licensed exclusive worldwide rights to develop and commercialize Infinity’s oncology product candidate duvelisib (Press release, Infinity Pharmaceuticals, NOV 2, 2016, View Source [SID1234516168]). Duvelisib is an oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma being investigated for the treatment of hematologic cancers, including chronic lymphocytic leukemia (CLL), indolent non-Hodgkin lymphoma (iNHL) and T cell lymphomas. Verastem will pay to Infinity up to $28 million in milestones, with positive data from DUO, a Phase 3, randomized monotherapy study of duvelisib in patients with relapsed/refractory CLL, triggering the first milestone payment, and royalties on net sales.

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"Duvelisib is a clinically validated, late-stage product candidate with a proven mechanism of action. This transaction has an attractive risk/reward profile given the modest financial investment prior to obtaining topline data from the DUO study, currently anticipated in the first half of 2017, as well as the potential applications for a variety of other lymphoid malignancies," said Robert Forrester, President and Chief Executive Officer of Verastem. "Duvelisib complements Verastem’s oncology pipeline by augmenting our strategic focus of developing small molecule agents that target malignant cells both directly and through modulation of the tumor microenvironment. This transaction represents a positive step toward our goal of bringing new treatment options to patients with cancer. We are working closely with Infinity to ensure a smooth transition of the duvelisib program."

"The potential of duvelisib is supported by clinical data demonstrating anti-cancer activity and a manageable safety profile in a wide range of lymphoid malignancies, including relapsed/refractory iNHL, CLL and T cell lymphomas," said Gregory I. Berk, MD, Chief Medical Officer of Verastem. "While there have been significant advances recently in the treatment of lymphoid malignancies, not all patients experience benefits or can tolerate these treatments. There remains a need for new oral medicines, and the targeted inhibition of PI3K-delta and PI3K-gamma brings a unique approach designed to address both the malignant B cell and its supportive microenvironment. We look forward to reporting data from the DUO study, which could enable a submission for regulatory approval."

"Infinity has always been committed to finding innovative ways to develop novel medicines which hold significant promise for people living with cancer. Verastem provides duvelisib the best opportunity to advance toward regulatory filings and potential commercialization given their oncology-focused capabilities and deep knowledge of the tumor microenvironment," stated Adelene Perkins, President and Chief Executive Officer of Infinity. "Additionally, the license of duvelisib fulfills an important strategic goal for Infinity by preserving cash while enabling our shareholders to participate in the value of the duvelisib program through potential milestone payments and royalties to Infinity."

Terms of Transaction

Under the terms of the license agreement, Verastem is obligated to pay to Infinity up to $28 million in milestones. Infinity is entitled to receive two milestone payments, $6 million upon positive data from the DUO study and $22 million upon the first regulatory approval inside or outside of the U.S. Verastem will also pay Infinity tiered mid-to-high single-digit royalties on net sales and will be responsible for the single-digit-royalty on net sales of duvelisib owed by Infinity to MundiPharma International Corporation Limited and Purdue Pharmaceutical Products L.P.

Verastem’s Expanded Oncology Pipeline

In addition to duvelisib, Verastem also holds worldwide rights to the tumor microenvironment-targeting focal adhesion kinase (FAK) inhibitors defactinib (VS-6063) and VS-4718. Verastem’s lead FAK inhibitor, defactinib, is currently being evaluated in three separate clinical collaborations in combination with immunotherapeutic agents for the treatment of several different cancer types, including pancreatic, ovarian, non-small cell lung cancer, and mesothelioma. These studies are combination clinical trials with pembrolizumab or avelumab from Merck & Co. and Pfizer/Merck KGaA, respectively. Verastem also owns rights to the FAK inhibitor VS-4718 and the dual PI3K and mTORC1/2 inhibitor VS-5584 which are both currently being evaluated in Phase 1 clinical studies.

Financial Guidance

Based on current operating plans including duvelisib, Verastem expects to have sufficient cash, cash equivalents and short-term investments to fund its research and development programs and operations into 2018.

Conference Call Information

Verastem will host a conference call on November 2, 2016, at 8:30 a.m. ET to discuss the license agreement announced today. The call can be accessed by dialing 877-341-5660 (U.S. and Canada) or 315-625-3226 (international), and entering passcode 12230467. To access the live webcast, please use either the following link: View Source or visit the investors section of the Verastem website at www.verastem.com. A replay of the call will be available on the Company’s website for a period of 180 days from today.

About the Tumor Microenvironment

The tumor microenvironment encompasses various cellular populations and extracellular matrices within the tumor or cancer niche that support cancer cell survival. This includes immunosuppressive cell populations such as regulatory T cells, myeloid-derived suppressor cells, M2 tumor-associated macrophages, as well as tumor-associated fibroblasts and extracellular matrix proteins which can hamper the entry and therapeutic benefit of cytotoxic immune cells and anti-cancer drugs. In addition to targeting the proliferative and survival signaling of cancer cells, Verastem’s compounds duvelisib, defactinib, VS-4718 and VS-5584 also target the tumor microenvironment as a mechanism of action to potentially improve a patient’s response to therapy.

About Duvelisib

Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes that are known to help support the growth and survival of malignant B cells and T cells. PI3K signaling may lead to the proliferation of malignant B cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage clinical trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed/refractory chronic lymphocytic leukemia (CLL)4, and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL) that achieved its primary endpoint of overall response rate upon topline analysis of efficacy data5. Duvelisib is also being evaluated for the treatment of hematologic malignancies through investigator-sponsored studies, including T cell lymphoma.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.

About Defactinib

Defactinib (VS-6063) is an investigational inhibitor of Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase encoded by the PTK-2 gene that mediates oncogenic signaling in response to cellular adhesion and growth factors.7 Based on the multi-faceted roles of FAK, defactinib is used to treat cancer through modulation of the tumor microenvironment, enhancement of anti-tumor immunity, and reduction of cancer stem cells.8,9 Defactinib is currently being evaluated in three separate clinical collaborations in combination with immunotherapeutic agents for the treatment of several different cancer types including pancreatic, ovarian, non-small cell lung cancer, and mesothelioma. These studies are combination clinical trials with pembrolizumab and avelumab from Merck & Co. and Pfizer/Merck KGaA, respectively.10,11,12 Information about these and additional clinical trials evaluating the safety and efficacy of defactinib can be found on www.clinicaltrials.gov.