New Data Presentations at SITC 2016 Annual Meeting Highlight Bristol-Myers Squibb’s Leadership in Advancing the Science of Immuno-Oncology Combinations

On November 2, 2016 Bristol-Myers Squibb Company (NYSE:BMY) reported new data evaluating the combination of Opdivo (nivolumab) plus Yervoy (ipilimumab) and Opdivo plus new investigational Immuno-Oncology assets, including lirilumab, will be presented at the 2016 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 31st Annual Meeting from November 9 – 11 in National Harbor, Maryland (Press release, Bristol-Myers Squibb, NOV 2, 2016, View Source [SID1234516183]). These presentations underscore Bristol-Myers Squibb’s dedication to investigating complementary Immuno-Oncology compounds that target different immune system pathways, including the ongoing study of Opdivo and Yervoy, with the goal of discovering transformational combinations that may offer the most significant improvements in overall survival and address areas of high unmet patient need.

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"We look forward to presenting new data at SITC (Free SITC Whitepaper) from our innovative Immuno-Oncology pipeline," said Fouad Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb. "Research has shown that targeting multiple immune system pathways may enhance anti-tumor responses, and there are a vast number of combinations to explore. We are committed to discovering novel pathways and complementary mechanisms that have the potential to significantly improve the standard of care in a broad range of tumor types."

Bristol-Myers Squibb is focused on developing transformational Immuno-Oncology combination therapies and expects to have 13 Immuno-Oncology compounds and seven targeted oncology compounds in the clinic by early 2017.

A listing of late-breaking and oral presentations is included below:

Late-Breaking Oral Presentations

Preliminary efficacy from a Phase 1/2 study of the natural killer cell–targeted antibody, lirilumab in combination with nivolumab in squamous cell carcinoma of the head and neck
Author: R. Leidner
Poster #456
Oral Late Breaking Abstract Session II
Saturday, November 12 at 11:15 – 11:30 am/EST
Efficacy and safety of nivolumab plus ipilimumab in metastatic urothelial carcinoma: First results from the Phase I/II CheckMate 32 Study
Author: P. Sharma
Poster #449
Oral Late Breaking Abstract Session II
Saturday, November 12 at 11:30 – 11:45 am/EST
Oral Presentations

Clinical safety and efficacy assessment of the CD137 agonist urelumab alone and in combination with nivolumab in patients with hematologic and solid tumor malignancies
Author: E. Massarelli
Poster #239
Oral Presentation: Beyond Single Agents: The Future of Combination Immunotherapies
Saturday, November 12 at 10:40 – 10:55 am/EST
The full set of data to be presented at SITC (Free SITC Whitepaper) by Bristol-Myers Squibb also includes:

Initial experience administering BMS-986016, a monoclonal antibody that targets lymphocyte activation gene (LAG)-3, alone and in combination with nivolumab to patients with hematologic and solid malignancies
Author: E. Lipson
Poster #238
Saturday, November 12 at 12 – 1 pm/EST
Enhanced vaccine-induced T-cell responses observed with ipilimumab (anti-CTLA-4) treatment in a nonhuman primate pharmacodynamic model
Author: J. Loffredo
Poster #102
Saturday, November 12 at 12 – 1 pm/EST
Assessing the potential for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) by combining the CD137 antibody urelumab with rituximab or cetuximab in patients with refractory lymphoma or select advanced solid tumors
Author: N. Segal
Poster #267
Friday, November 11 at 12:15 – 1:30 pm/EST
Bristol-Myers Squibb: At the Forefront of Immuno-Oncology Science & Innovation

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines that will raise survival expectations in hard-to-treat cancers and will change the way patients live with cancer.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational and approved agents – including the first combination of two I-O agents in metastatic melanoma – and our differentiated clinical development program, which is studying broad patient populations across more than 20 types of cancers with 12 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs uniquely position us to advance the science of combinations across multiple tumors and potentially deliver the next wave of I-O combination regimens with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and inform which patients will benefit most from I-O therapies.

We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part, but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 57 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 47 countries, including the United States and the European Union.

U.S. FDA APPROVED INDICATIONS FOR OPDIVO

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Please refer to the end of the Important Safety Information for a brief description of the patient populations studied in the CheckMate trials.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been reported. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more severe pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In patients receiving OPDIVO monotherapy, fatal cases of immune-mediated pneumonitis have occurred. Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 4.9% (13/263) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon re-initiation of OPDIVO. When administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated colitis occurred in 26% (107/407) of patients including three fatal cases.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal (diarrhea of ≥7 stools above baseline, fever, ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred in 34 (7%) patients. Across all YERVOY-treated patients in that study (n=511), 5 (1%) developed intestinal perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated hepatitis occurred in 13% (51/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the ULN or total bilirubin elevations >3x the ULN; Grade 3-5) occurred in 8 (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in 0.4%.

Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor neuropathy were reported.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal insufficiency, autoimmune thyroid disorders, and Type 1 diabetes mellitus. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency, thyroid function prior to and periodically during treatment, and hyperglycemia. Administer hormone replacement as clinically indicated and corticosteroids for Grade 2 or greater hypophysitis. Withhold for Grade 2 or 3 and permanently discontinue for Grade 4 hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently discontinue for Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients. In patients receiving OPDIVO with YERVOY, hypophysitis occurred in 9% (36/407) of patients. In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of patients. In patients receiving OPDIVO with YERVOY, adrenal insufficiency occurred in 5% (21/407) of patients. In patients receiving OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in hypothyroidism occurred in 22% (89/407) of patients. Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe to life-threatening immune-mediated endocrinopathies (requiring hospitalization, urgent medical intervention, or interfering with activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. 6 of the 9 patients were hospitalized for severe endocrinopathies.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for elevated serum creatinine prior to and periodically during treatment. Administer corticosteroids for Grades 2-4 increased serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 increased serum creatinine. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407) of patients.

Immune-Mediated Skin Adverse Reactions and Dermatitis

OPDIVO can cause immune-mediated rash, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with fatal outcome. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient for specialized care for assessment and treatment; if confirmed, permanently discontinue. In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients. In patients receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6% (92/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening, or fatal immune-mediated dermatitis (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13 (2.5%) patients. 1 (0.2%) patient died as a result of toxic epidermal necrolysis. 1 additional patient required hospitalization for severe dermatitis.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients with neurologic symptoms may include, but not be limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Withhold OPDIVO in patients with new-onset moderate to severe neurologic signs or symptoms and evaluate to rule out other causes. If other etiologies are ruled out, administer corticosteroids and permanently discontinue OPDIVO for immune-mediated encephalitis. In patients receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of patients. Fatal limbic encephalitis occurred in one patient after 7.2 months of exposure despite discontinuation of OPDIVO and administration of corticosteroids. Encephalitis occurred in one patient receiving OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.

Other Immune-Mediated Adverse Reactions

Based on the severity of adverse reaction, permanently discontinue or withhold treatment, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO the following clinically significant immune-mediated adverse reactions occurred in <1.0% of patients receiving OPDIVO: uveitis, iritis, pancreatitis, facial and abducens nerve paresis, demyelination, polymyalgia rheumatica, autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), myositis, myocarditis, rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome.

Infusion Reactions

OPDIVO can cause severe infusion reactions, which have been reported in <1.0% of patients in clinical trials. Discontinue OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of infusion in patients with Grade 1 or 2. In patients receiving OPDIVO monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of patients. In patients receiving OPDIVO with YERVOY, infusion-related reactions occurred in 2.5% (10/407) of patients.

Complications of Allogeneic HSCT after OPDIVO

Complications, including fatal events, occurred in patients who received allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients from Checkmate 205 and 039, who underwent allogeneic HSCT after discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with myeloablative conditioning). Thirty-five percent (6/17) of patients died from complications of allogeneic HSCT after OPDIVO. Five deaths occurred in the setting of severe or refractory GVHD. Grade 3 or higher acute GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome, without an identified infectious cause, was reported in 35% (n=6) of patients. Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic encephalitis without an identified infectious cause, and Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive disease (VOD) occurred in one patient, who received reduced-intensity conditioned allogeneic HSCT and died of GVHD and multi-organ failure. Other cases of hepatic VOD after reduced-intensity conditioned allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor blocking antibody before transplantation. Cases of fatal hyperacute GVHD have also been reported. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic HSCT.

Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene promptly.

Embryo-Fetal Toxicity

Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with an OPDIVO- or YERVOY- containing regimen and for at least 5 months after the last dose of OPDIVO.

Lactation

It is not known whether OPDIVO or YERVOY is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from an OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment. Advise women to discontinue nursing during treatment with YERVOY and for 3 months following the final dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase. In Checkmate 066, serious adverse reactions occurred in 36% of patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions occurred in 41% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in ≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73% and 37%), adverse reactions leading to permanent discontinuation (43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4 adverse reactions (72% and 44%) all occurred more frequently in the OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in ≥2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, among all patients (safety population [n=263]), adverse reactions leading to discontinuation (4.2%) or to dosing delays (23%) occurred. The most frequent serious adverse reactions reported in ≥1% of patients were infusion-related reaction, pneumonia, pleural effusion, pyrexia, rash and pneumonitis. Ten patients died from causes other than disease progression, including 6 who died from complications of allogeneic HSCT. Serious adverse reactions occurred in 21% of patients in the safety population (n=263) and 27% of patients in the subset of patients evaluated for efficacy (efficacy population [n=95]).

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 025, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, among all patients (safety population [n=263]) and the subset of patients in the efficacy population (n=95), respectively, the most common adverse reactions (≥20%) were fatigue (32% and 43%), upper respiratory tract infection (28% and 48%), pyrexia (24% and 35%), diarrhea (23% and 30%), and cough (22% and 35%). In the subset of patients in the efficacy population (n=95), the most common adverse reactions also included rash (31%), musculoskeletal pain (27%), pruritus (25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%).

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

CHECKMATE Trials and Patient Populations

CheckMate 067 – advanced melanoma alone or in combination with YERVOY; CheckMate 037 and 066 – advanced melanoma; CheckMate 017 – squamous non-small cell lung cancer (NSCLC); CheckMate 057 – non-squamous NSCLC; CheckMate 025 – renal cell carcinoma; CheckMate 205/039 – classical Hodgkin lymphoma.

Please see U.S. Full Prescribing Information, including Boxed WARNING regarding immune-mediated adverse reactions, for YERVOY.

Please see U.S. Full Prescribing Information for OPDIVO.

Alkermes plc Reports Third Quarter 2016 Financial Results

On November 2, 2016 Alkermes plc (NASDAQ: ALKS) reported financial results for the third quarter of 2016 (Press release, Alkermes, NOV 2, 2016, View Source;p=RssLanding&cat=news&id=2218397 [SID1234516175]).

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"Our third quarter results demonstrate the value of our highly-diversified commercial portfolio, and were driven by the strong growth of our proprietary products, VIVITROL and ARISTADA," commented James Frates, Chief Financial Officer of Alkermes. "As we approach year-end, we remain well-positioned to execute on our business strategy and are reiterating our 2016 financial expectations provided in July."

"We are at an unprecedented place in Alkermes’ evolution, with two proprietary products growing in their markets, ALKS 5461 advancing at full speed, and two additional late-stage candidates well into their pivotal programs," stated Richard Pops, Chief Executive Officer of Alkermes. "VIVITROL for opioid and alcohol dependence and ARISTADA for schizophrenia are important, distinctive medicines in their disease areas and are the foundation of our future growth. With the positive results of FORWARD-5 for ALKS 5461 for major depressive disorder in hand, Alkermes’ next potential growth driver is coming more clearly into focus."

Quarter Ended Sept. 30, 2016 Highlights

Total revenues for the quarter were $180.2 million. This compared to $152.7 million for the same period in the prior year.
Net loss according to generally accepted accounting principles in the U.S. (GAAP) was $62.7 million, or a basic and diluted GAAP loss per share of $0.41, for the quarter, which reflected increased investment in the company’s advancing late-stage pipeline and commercial infrastructure. This compared to GAAP net loss of $81.0 million, or a basic and diluted GAAP loss per share of $0.54, for the same period in the prior year.
Non-GAAP net loss was $14.1 million, or a non-GAAP basic and diluted loss per share of $0.09, for the quarter. This compared to non-GAAP net loss of $28.8 million, or a non-GAAP basic and diluted loss per share of $0.19, for the same period in the prior year.
Quarter Ended Sept. 30, 2016 Financial Results

Revenues

Net sales of VIVITROL were $55.8 million, compared to $37.9 million for the same period in the prior year, representing an increase of approximately 47%.
Net sales of ARISTADA were $14.0 million, up from $10.3 million in the second quarter of 2016.
Manufacturing revenues from RISPERDAL CONSTA (risperidone) and royalty revenues from RISPERDAL CONSTA, INVEGA SUSTENNA/XEPLION (paliperidone palmitate) and INVEGA TRINZA/TREVICTA (paliperidone palmitate) were $73.3 million, compared to $67.6 million for the same period in the prior year.
Manufacturing and royalty revenues from AMPYRA/FAMPYRA1 were $12.9 million, compared to $22.1 million for the same period in the prior year, primarily due to the timing of manufacturing shipments.
Royalty revenue from BYDUREON was $11.6 million, compared to $13.0 million for the same period in the prior year.
Costs and Expenses

Operating expenses were $241.4 million, reflecting increased investment in the company’s development pipeline, the continued launch of ARISTADA and growth of VIVITROL. Operating expenses for the quarter ended Sept. 30, 2015 were $230.1 million.
Balance Sheet
At Sept. 30, 2016, Alkermes had cash and total investments of $624.6 million, compared to $798.8 million at Dec. 31, 2015. On Sept. 26, 2016 the company retired $60 million of maturing debt. In October 2016, the company extended the maturity date of the approximately $286 million outstanding term loan by two years to Sept. 25, 2021.

Financial Expectations
Alkermes reiterates its Financial Expectations for 2016 set forth in its press release dated July 28, 2016.

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.