On October 28, 2015 Bristol-Myers Squibb Company (NYSE:BMY) reported that it received the Prix Galien USA 2015 Award for Best Biotechnology Product for Opdivo (nivolumab), the Company’s PD-1 immune checkpoint inhibitor (Press release, Bristol-Myers Squibb, OCT 28, 2015, View Source [SID:1234507813]). Bristol-Myers Squibb was recognized for its innovative discovery and development of Opdivo in approved indications for previously treated metastatic squamous non-small cell lung cancer (NSCLC), and in unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor, for which it received accelerated approval based on tumor response rate and durability of response. Since the submission for the Best Biotechnology Award, Opdivo has also been approved by the U.S. Food and Drug Administration (FDA) in the combination of Opdivo + Yervoy, the first FDA-approved regimen of two Immuno-Oncology agents, in BRAF V600 wild-type unresectable or metastatic melanoma, as well as for the treatment of patients with metastatic non-squamous NSCLC with progression on or after platinum-based chemotherapy.

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The announcement was made during the ninth annual Prix Galien USA Awards Ceremony held on October 27, 2015 in New York City. The Prix Galien USA Award, which is selected by a preeminent scientific committee that includes several Nobel Laureates, honors outstanding achievements in improving the human condition through the development of innovative therapies. This is the second honor received by Bristol-Myers Squibb in the Best Biotechnology Product category, making it the only company to receive this award for two Immuno-Oncology agents. In 2012, Yervoy received the award, following its initial approval for unresectable or metastatic melanoma. Building on this pioneering science, the Company continues to research the potential of Immuno-Oncology to extend survival in some of the hardest-to-treat cancers.

"We are pleased to be acknowledged for our Company’s scientific contributions to this historic time in cancer research, when the science of Immuno-Oncology is helping to change expectations in cancer care," said Francis Cuss, MB BChir, FRCP, executive vice president and chief scientific officer, Bristol-Myers Squibb. "Receiving the Prix Galien USA 2015 Award for Best Biotechnology Product underscores our efforts with the Opdivo early- and late-stage clinical program in patients with some of the hardest-to-treat cancers, like advanced melanoma and squamous non-small cell lung cancer."

About Opdivo

Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 8,000 patients have been enrolled worldwide.

Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world in July 2014, and currently has regulatory approval in more than 37 countries including the United States, Japan, and in the European Union.

In the U.S., Opdivo is indicated for patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. Opdivo is also approved for use in combination with Yervoy, for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma. These indications are approved under accelerated approval based on tumor response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials. Opdivo is also indicated in the U.S. 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.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions due to T-cell activation and proliferation. 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) 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

Immune-mediated pneumonitis or interstitial lung disease, including fatal cases, occurred with OPDIVO treatment. Across the clinical trial experience with solid tumors, fatal immune-mediated pneumonitis occurred in 0.5% (5/978) of patients receiving OPDIVO as a single agent. In Checkmate 037, pneumonitis, including interstitial lung disease, occurred in 3.4% (9/268) of patients receiving OPDIVO and none of the 102 patients receiving chemotherapy. Immune-mediated pneumonitis occurred in 2.2% (6/268) of patients receiving OPDIVO; Grade 3 (n=1) and Grade 2 (n=5). In Checkmate 057, immune-mediated pneumonitis, including interstitial lung disease, occurred in 3.4% (10/287) of patients receiving OPDIVO as a single agent: Grade 3 (n=5), Grade 2 (n=2), and Grade 1 (n=3). Across the clinical trial experience in 188 patients with melanoma who received OPDIVO in combination with YERVOY, in Checkmate 069 (n=94) and an additional dose-finding study (n=94), fatal immune-mediated pneumonitis occurred in 0.5% (1/188) of patients. In Checkmate 069, there were six additional patients who died without resolution of abnormal respiratory findings. Monitor patients for signs with radiographic imaging and symptoms of pneumonitis. Administer corticosteroids for Grade 2 or greater pneumonitis. Permanently discontinue for Grade 3 or 4 and withhold until resolution for Grade 2. In Checkmate 069, pneumonitis, including interstitial lung disease, occurred in 10% (9/94) of patients receiving OPDIVO in combination with YERVOY and 2.2% (1/46) of patients receiving YERVOY. Immune-mediated pneumonitis occurred in 6% (6/94) of patients receiving OPDIVO in combination with YERVOY: Grade 5 (n=1), Grade 3 (n=2) and Grade 2 (n=3).

Immune-Mediated Colitis

Immune-mediated colitis can occur with OPDIVO treatment. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. As a single agent, withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent colitis upon restarting OPDIVO. In combination with YERVOY, withhold OPDIVO for Grade 2 and permanently discontinue for Grade 3 or 4 or recurrent colitis upon restarting OPDIVO. In Checkmate 037, diarrhea or colitis occurred in 21% (57/268) of patients receiving OPDIVO and 18% (18/102) of patients receiving chemotherapy. Immune-mediated colitis occurred in 2.2% (6/268) of patients receiving OPDIVO; Grade 3 (n=5) and Grade 2 (n=1). In Checkmate 057, diarrhea or colitis occurred in 17% (50/287) of patients receiving OPDIVO as a single agent. Immune-mediated colitis occurred in 2.4% (7/287) of patients: Grade 3 (n=3), Grade 2 (n=2), and Grade 1 (n=2). In Checkmate 069, diarrhea or colitis occurred in 57% (54/94) of patients receiving OPDIVO in combination with YERVOY and 46% (21/46) of patients receiving YERVOY. Immune-mediated colitis occurred in 33% (31/94) of patients receiving OPDIVO in combination with YERVOY: Grade 4 (n=1), Grade 3 (n=16), Grade 2 (n=9), and Grade 1 (n=5).

In a separate YERVOY Phase 3 study, 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

Immune-mediated hepatitis can occur with OPDIVO treatment. 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 Checkmate 037, there was an increased incidence of liver test abnormalities in the OPDIVO-treated group as compared to the chemotherapy-treated group, with increases in AST (28% vs 12%), alkaline phosphatase (22% vs 13%), ALT (16% vs 5%), and total bilirubin (9% vs 0). Immune-mediated hepatitis occurred in 1.1% (3/268) of patients receiving OPDIVO; Grade 3 (n=2) and Grade 2 (n=1). In Checkmate 057, one patient (0.3%) developed immune-mediated hepatitis. In Checkmate 069, immune-mediated hepatitis occurred in 15% (14/94) of patients receiving OPDIVO in combination with YERVOY: Grade 4 (n=3), Grade 3 (n=9), and Grade 2 (n=2).

In a separate YERVOY Phase 3 study, 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 Dermatitis

In a separate YERVOY Phase 3 study, 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 Neuropathies

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

Immune-Mediated Endocrinopathies

Hypophysitis, adrenal insufficiency, and thyroid disorders can occur with OPDIVO treatment. Monitor patients for signs and symptoms of hypophysitis, signs and symptoms of adrenal insufficiency during and after treatment, and thyroid function prior to and periodically during treatment. Administer 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.

In Checkmate 069, hypophysitis occurred in 13% (12/94) of patients receiving OPDIVO in combination with YERVOY: Grade 3 (n=2) and Grade 2 (n=10). Adrenal insufficiency occurred in 1% (n=555) of patients receiving OPDIVO as a single agent. In Checkmate 069, adrenal insufficiency occurred in 9% (8/94) of patients receiving OPDIVO in combination with YERVOY: Grade 3 (n=3), Grade 2 (n=4), and Grade 1 (n=1). In Checkmate 069, hypothyroidism occurred in 19% (18/94) of patients receiving OPDIVO in combination with YERVOY. All were Grade 1 or 2 in severity except for one patient who experienced Grade 3 autoimmune thyroiditis. Grade 1 hyperthyroidism occurred in 2.1% (2/94) of patients receiving OPDIVO in combination with YERVOY. In Checkmate 037, Grade 1 or 2 hypothyroidism occurred in 8% (21/268) of patients receiving OPDIVO and none of the 102 patients receiving chemotherapy. Grade 1 or 2 hyperthyroidism occurred in 3% (8/268) of patients receiving OPDIVO and 1% (1/102) of patients receiving chemotherapy. In Checkmate 057, Grade 1 or 2 hypothyroidism, including thyroiditis, occurred in 7% (20/287) and elevated TSH occurred in 17% of patients receiving OPDIVO as a single agent. Grade 1 or 2 hyperthyroidism occurred in 1.4% (4/287) of patients.

In a separate YERVOY Phase 3 study, 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

Immune-mediated nephritis can occur with OPDIVO treatment. Monitor patients for elevated serum creatinine prior to and periodically during treatment. For Grade 2 or 3 increased serum creatinine, withhold and administer corticosteroids; if worsening or no improvement occurs, permanently discontinue. Administer corticosteroids for Grade 4 serum creatinine elevation and permanently discontinue. In Checkmate 037, there was an increased incidence of elevated creatinine in the OPDIVO-treated group as compared to the chemotherapy-treated group (13% vs 9%). Grade 2 or 3 immune-mediated nephritis or renal dysfunction occurred in 0.7% (2/268) of patients. In Checkmate 057, Grade 2 immune-mediated renal dysfunction occurred in 0.3% (1/287) of patients receiving OPDIVO as a single agent. In Checkmate 069, Grade 2 or higher immune-mediated nephritis or renal dysfunction occurred in 2.1% (2/94) of patients. One patient died without resolution of renal dysfunction.

Immune-Mediated Rash

Immune-mediated rash can occur with OPDIVO treatment. Monitor patients for rash. Administer corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and permanently discontinue for Grade 4. In Checkmate 037 (n=268), the incidence of rash was 21%; the incidence of Grade 3 or 4 rash was 0.4%. In Checkmate 057, immune-mediated rash occurred in 6% (17/287) of patients receiving OPDIVO as a single agent including four Grade 3 cases. In Checkmate 069, immune-mediated rash occurred in 37% (35/94) of patients receiving OPDIVO in combination with YERVOY: Grade 3 (n=6), Grade 2 (n=10), and Grade 1 (n=19).

Immune-Mediated Encephalitis

Immune-mediated encephalitis can occur with OPDIVO treatment. 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. Across clinical trials of 8490 patients receiving OPDIVO as a single agent or in combination with YERVOY, <1% of patients were identified as having encephalitis. In Checkmate 057, fatal limbic encephalitis occurred in one patient (0.3%) receiving OPDIVO as a single agent.

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. The following clinically significant immune-mediated adverse reactions occurred in <2% (n=555) of single-agent OPDIVO-treated patients: uveitis, pancreatitis, abducens nerve paresis, demyelination, polymyalgia rheumatica, and autoimmune neuropathy. Across clinical trials of OPDIVO administered as a single agent at doses 3 mg/kg and 10 mg/kg, additional clinically significant, immune-mediated adverse reactions were identified: facial nerve paralysis, motor dysfunction, vasculitis, diabetic ketoacidosis, and myasthenic syndrome. In Checkmate 069, the following additional immune-mediated adverse reactions occurred in 1% of patients treated with OPDIVO in combination with YERVOY: Guillain-Barré syndrome and hypopituitarism. Across clinical trials of OPDIVO in combination with YERVOY, the following additional clinically significant, immune-mediated adverse reactions were identified: uveitis, sarcoidosis, duodenitis, pancreatitis, and gastritis.

Infusion Reactions

Severe infusion reactions have been reported in <1% of patients in clinical trials of OPDIVO as a single agent. In Checkmate 057, Grade 2 infusion reactions occurred in 1% (3/287) of patients receiving OPDIVO as a single agent. In Checkmate 069, Grade 2 infusion reactions occurred in 3% (3/94) of patients receiving OPDIVO in combination with YERVOY. Discontinue OPDIVO in patients with severe or life-threatening infusion reactions. Interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions.

Embryofetal Toxicity

Based on its mechanism of action, OPDIVO 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 OPDIVO-containing regimen and for at least 5 months after the last dose of OPDIVO.

Lactation

It is not known whether OPDIVO 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 OPDIVO-containing regimen, advise women to discontinue breastfeeding during treatment.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO. 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 057, serious adverse reactions occurred in 47% of patients receiving OPDIVO as a single agent. The most frequent serious adverse reactions reported in ≥2% of patients were pneumonia, pulmonary embolism, dyspnea, pleural effusion, and respiratory failure. In Checkmate 069, serious adverse reactions occurred in 62% of patients receiving OPDIVO; the most frequent serious adverse events with OPDIVO in combination with YERVOY, as compared to YERVOY alone, were colitis (17% vs 9%), diarrhea (9% vs 7%), pyrexia (6% vs 7%), and pneumonitis (5% vs 0).

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with OPDIVO was rash (21%). In Checkmate 057, the most common adverse reactions (≥20%) reported with OPDIVO as a single agent were fatigue (49%), musculoskeletal pain (36%), cough (30%), decreased appetite (29%), and constipation (23%). In Checkmate 069, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO in combination with YERVOY vs YERVOY alone were rash (67% vs 57%), pruritus (37% vs 26%), headache (24% vs 20%), vomiting (23% vs 15%), and colitis (22% vs 11%).

In a separate YERVOY Phase 3 study, 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%).

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

On October 28, 2015 CytRx Corporation (Nasdaq: CYTR), a biopharmaceutical research and development company specializing in oncology, reported that a poster titled "A Phase 1b/2 Study of Aldoxorubicin plus Ifosfamide/Mesna in Untreated Sarcoma Patients" will be presented at the 20th Annual Connective Tissue Oncology Society (CTOS) Annual Meeting in Salt Lake City, Utah, November 4 – 7, 2015 (Press release, CytRx, OCT 28, 2015, View Source;p=RssLanding&cat=news&id=2103413 [SID:1234507814]). The poster will discuss the trial design and current results of CytRx’s on-going clinical trial in patients with metastatic soft and non-soft tissue sarcomas. In this study, 7 subjects received 170 mg/m2 aldoxorubicin, and 3 subjects received 250 mg/m2 aldoxorubicin (125 or 185 mg/m2 doxorubicin equivalents), administered intravenously every 4 weeks. All patients also received 1 gram/m2/day ifosfamide/mesna administered as a continuous 24 hour infusion for up to 14 days, every 4 weeks. As of September 30, 2015, 8 subjects demonstrated tumor shrinkage, with 3 subjects having documented partial responses. Six subjects are still receiving treatment. Grade 3 or 4 adverse events included neutropenia (90%), anemia (70%), nausea or vomiting (10%) and febrile neutropenia (10%). No subject exhibited cardiotoxicity by echocardiogram.

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Dr. Sant Chawla M.D., F.R.A.C.P., Director of the Sarcoma Oncology Center and principal investigator for this trial stated, "The use of doxorubicin with ifosfamide and mesna remains a treatment option for many sarcoma patients. Replacing doxorubicin with aldoxorubicin may lead to improved clinical outcomes for these first-line sarcoma patients, since we already know that aldoxorubicin demonstrated superiority to doxorubicin in the previously completed Phase 2b trial in first-line tissue sarcomas."

"The presentation of the Phase 1b/2 clinical trial data at CTOS demonstrates to the sarcoma community the potential use of aldoxorubicin as part of a multi-drug regimen to treat sarcomas," said Steven A. Kriegsman, CytRx’s Chairman and Chief Executive Officer. "The on-going trial will generate important dosing, safety and efficacy data in treatment-naive patients. We remain excited about the prospects of aldoxorubicin in our pivotal global Phase 3 trial in sarcoma patients that have previously received chemotherapy, with top-line data expected in the second half of 2016."

Phase 1b/2 Trial Design

Aldoxorubicin is administered at escalating doses by intravenous infusion (IVI) on Day 1 every 28 days, and 1 gm/m2/day of ifosfamide and an equivalent dose of mesna is administered via continuous infusion with a portable at-home pump for up to 14 days every 28 days starting on Day 1 of each cycle, until disease progression, unacceptable toxicity or the patient withdraws consent. The primary objective of the trial is to determine the preliminary safety of administration of aldoxorubicin in combination with ifosfamide in patients with metastatic, locally advanced, or unresectable STS as measured by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, vital signs, echocardiograms (ECHO) or multiple-gated acquisition (MUGA) scans, electrocardiogram (ECG) results, and weight. The secondary objective of the trial is to evaluate the activity of aldoxorubicin in combination with ifosfamide/mesna in this population, assessed by overall response rate (ORR), progression-free survival (PFS) and PFS at 4 and 6 months. This Phase 1b/2 trial is being conducted at the Sarcoma Oncology Center in Santa Monica, California.

About Soft Tissue Sarcoma

Soft tissue sarcoma is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue, and can arise anywhere in the body at any age. According to the American Cancer Society, there are approximately 50 types of soft tissue sarcomas. In 2015 more than 11,900 new cases were diagnosed in the U.S. and approximately 4,900 Americans died from this disease. In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market.

About Aldoxorubicin

The widely used chemotherapeutic agent doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to circulating albumin, the most plentiful protein in the bloodstream. Protein-hungry tumors concentrate albumin, thus increasing the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. This allows for greater doses (3 ½ to 4 times) of doxorubicin to be administered while reducing its toxic side effects. In studies thus far there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 2,000 mg/m2.

On October 28, 2015 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy for the treatment of advanced melanoma and metastatic non-small cell lung cancer in patients whose disease has progressed after other therapies, received the Prix Galien USA 2015 Award for Best Biotechnology Product (Press release, Merck & Co, OCT 28, 2015, View Source [SID:1234507818]).

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"As a company built on a foundation of scientific excellence, Merck is honored to again have been chosen as a recipient of this prestigious award," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "This achievement is a testament to the remarkable contributions of everyone at Merck, as well as the many physicians and patients who participated in our clinical trials, in helping to bring KEYTRUDA to patients."

The Prix Galien Award recognizes the pharmaceutical industry’s outstanding achievement in the development of new medicines. An internationally recognized award, the Prix Galien was founded in France in 1969 by French pharmacist Roland Mehl and is considered the highest accolade for pharmaceutical research and development.

This latest award for KEYTRUDA is Merck’s seventh Prix Galien USA award in nine years. The company was previously recognized for ZOSTAVAX (2013), VICTRELIS (2012), ROTATEQ (2010), ISENTRESS (2008) and JANUVIA and GARDASIL (2007). In total, around the world, Merck has won the Prix Galien 40 times, making Merck the most-awarded company of all time.

On October 27, 2015 Prima BioMed Ltd (ASX: PRR; NASDAQ: PBMD), a leading immuno-oncology company, reported that it is pleased to announce its first regulatory approval facilitating commencement of the landmark Phase IIb clinical study of IMP321, Prima’s lead compound (Filing, 6-K, Prima Biomed, OCT 27, 2015, View Source [SID:1234507819]).

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The AIPAC (Active Immunotherapy PAClitaxel) clinical trial application has been cleared by Belgium’s Federal Agency for Medicines and Health Products (FAMHP). AIPAC is a multi-national, randomized, double-blind, placebo-controlled Phase IIb study of IMP321 in metastatic breast cancer which has received Scientific Advice from the European Medicines Agency (EMA). Prima continues work to obtain ethics approval by the Institutional Review Boards (IRB) at the chosen study sites in Belgium. IRB approval is the final approval required before trial initiation.

Prima’s CSO & CMO, Dr. Frédéric Triebel said, ‘Prima BioMed has, over the last 10 months, assembled a first class team to work on AIPAC. The clearing of our study protocol by FAMHP represents a big step forward for the team and we are on track to commence the study by the end of 2015.’

AIPAC – A key study
IMP321, a first-in-class Antigen Presenting Cell (APC) activator based on the immune checkpoint LAG-3, represents one of the first proposed active immunotherapy drugs in which the patient’s own immune system is harnessed to respond to tumour antigenic debris created by chemotherapy. As an APC activator IMP321 boosts the network of dendritic cells in the body that can respond to tumour antigens for a better anti-tumour CD8 T cell response.

IMP321 has been shown in an open-label Phase I study1 to be able to double the expected six-month response rate in HER-2 negative metastatic breast cancer patients receiving standard-of-care paclitaxel, from a 25% historic response rate2 (RECIST criteria) to 50% when combined with IMP321. AIPAC has been designed to confirm this expected response and evaluate its effect on patient survival in a randomized, double blind, placebo-controlled setting and in a comparable patient population. Progression-Free Survival (PFS) will be AIPAC’s primary endpoint. RECIST response rates and Overall Survival are among the secondary endpoints. The design of the study has been examined by the EMA’s Scientific Advice expert panel in the view of using these data for Marketing Authorization in the EU in tested setting.

The protocol that arose from Prima’s interaction with the EMA will see women recruited into AIPAC with metastatic breast cancer where the tumour is HER-2-negative but hormone receptor positive. These patients will be receiving paclitaxel as first line chemotherapy after having failed on hormone therapy. They will represent a large patient population (hormone receptor-positive breast cancer is accounting for app. 75 percent of all cases) for which there are few viable treatment options, as indicated by the fact that PFS in such patients can be as low as six months3.

In the AIPAC study, patients will be administered subcutaneous doses of IMP321 on days 2 and 16 of a weekly regimen of paclitaxel, the day after their paclitaxel infusion.

AIPAC will aim to initially recruit 15 patients for a smaller safety run-in in three different countries. This section of the trial will test in combination with paclitaxel the safety of IMP321 in doses up to 30 mg per dose, which has previously been shown to be safe when tested as a monotherapy4 and is significantly higher than the maximum 6.25 mg dose from the Phase I in metastatic breast cancer. This section of AIPAC, extending into 2016, and will yield valuable safety, pharmacokinetic and pharmacodynamic data that Prima expects to report in second half of 2016.

After the safety run-in the AIPAC investigators will proceed to recruit 196 patients, randomising them 1:1 to either standard-of-care paclitaxel plus placebo or paclitaxel plus IMP321 for six months as per the Phase I dosing regimen, after which the responding or stable patients will be maintained for another year with monthly IMP321 injections. The study has been powered to show a four-month PFS advantage for the treatment group. Allowing time for patient recruitment and follow-up, AIPAC’s expected duration is around three years. Throughout the study, an independent data monitoring committee will review patient safety, survival rates and demographics at regular intervals. No interim statistical analysis is planned.

Prima envisages setting up at least 30 study sites for AIPAC in six European countries – starting with Belgium, France and the Netherlands. While Belgian regulatory approval has now been received for AIPAC, the relevant approvals are still to be obtained for the other countries.

On October 27, 2015 United Therapeutics Corporation (NASDAQ: UTHR) reported its financial results for the third quarter ended September 30, 2015 (Press release, United Therapeutics, OCT 27, 2015, View Source [SID:1234507917]).

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"We are pleased with our third quarter 2015 results as total revenues reached $386 million and each of our pulmonary arterial hypertension products realized their highest revenue levels ever," said Roger Jeffs, Ph.D., United Therapeutics’ President and Co-Chief Executive Officer. "We are also happy to report the first commercial sales of Unituxin for the treatment of high-risk neuroblastoma. These strong financial results will enable us to continue advancing our innovative product pipeline and returning value to our shareholders through our recently announced $500 million share repurchase program."

Financial Results for the Three Months Ended September 30, 2015

Revenues

Revenues for the three months ended September 30, 2015 increased by $56.3 million, compared to the three months ended September 30, 2014. The growth in revenues primarily resulted from: (1) a $22.6 million increase in Adcirca revenues, driven by price increases, which are determined by Eli Lilly and Company, and by an increase in the number of Adcirca bottles sold; and (2) a $19.9 million increase in Orenitram revenues due to an increase in the number of patients being treated. In addition, $4.7 million of the increase in revenue was due to our first commercial sales of Unituxin, which commenced during the three months ended September 30, 2015.

Expenses

Research and development expense.

Share-based compensation. The decrease in share-based compensation of $113.6 million for the three months ended September 30, 2015, compared to the same three-month period in 2014, was primarily due to a 25 percent decrease in our stock price during the quarter ended September 30, 2015, compared to a 45 percent increase during the same quarter in 2014.

General and administrative. The decrease in general and administrative expense of $12.8 million for the three months ended September 30, 2015, compared to the same three-month period in 2014, resulted from a $13.0 million decrease in grants to non-profit organizations that provide financial assistance to patients with pulmonary arterial hypertension.

Share-based compensation. The decrease in share-based compensation of $208.8 million for the three months ended September 30, 2015, compared to the same three-month period in 2014, was primarily due to a 25 percent decrease in our stock price during the quarter ended September 30, 2015, as compared to a 45 percent increase during the same quarter in 2014.

Cost of product sales. The decrease in cost of product sales for the three months ended September 30, 2015, compared to the three months ended September 30, 2014, was due to the expiration of our royalty obligation to GlaxoSmithKline plc in October 2014. During the three months ended September 30, 2014, we incurred $24.9 million in royalty expense related to this royalty obligation.

Share-based compensation. The decrease in share-based compensation of $16.9 million for the three months ended September 30, 2015, compared to the same three-month period in 2014, was primarily due to a 25 percent decrease in our stock price during the quarter ended September 30, 2015, as compared to a 45 percent increase during the same quarter in 2014.

Gain on Sale of Intangible Asset

In September 2015, we sold the Rare Pediatric Priority Review Voucher (PPRV) we received from the FDA in connection with the approval of our Biologics License Application for Unituxin. In exchange for the voucher, we received $350.0 million from AbbVie Ireland Unlimited Company (AbbVie), a wholly-owned subsidiary of AbbVie Inc. The proceeds from the sale of the PPRV were recognized as a gain on the sale of an intangible asset, as the PPRV did not have a carrying value on our consolidated balance sheet at the time of sale.

Income Tax Expense

The provision for income tax expense is based on an estimated annual effective tax rate that is subject to adjustment in subsequent quarterly periods if components used to estimate the annual effective tax rate are updated or revised. Our estimated annual effective tax rates were approximately 38 percent and approximately 36 percent as of September 30, 2015 and September 30, 2014, respectively. Our 2015 estimated annual effective tax rate increased as of September 30, 2015 primarily due to a decrease in the estimated general business credits as compared to the prior year.

Non-GAAP Earnings

Non-GAAP earnings is defined as net income, adjusted for the following charges, which are presented net of our annual effective income tax rate, as applicable: (1) interest expense; (2) license fees; (3) depreciation and amortization; (4) impairment charges; and (5) share-based compensation expense (stock option, share tracking award and employee stock purchase plan). For 2015, we also adjusted non-GAAP earnings to eliminate the gain (net of our annual effective income tax rate) resulting from the sale of the PPRV in September 2015.