On December 13, 2017 MolMed S.p.A. (MLM.MI) reported that it obtained its first national marketing authorization for its proprietary product, Zalmoxis: the Board of Directors of AIFA (Agenzia Italiana del Farmaco) approved the agreement negotiated between AIFA’s Prices and Reimbursement Committee (CPR) and MolMed, in which the price and reimbursement for Zalmoxis medicinal product were defined (Press release, MolMed, DEC 13, 2017, View Source [SID1234595072]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Zalmoxis is MolMed’s first patient specific cell therapy product, based on genetically engineering of the immune system, administered following haploidentical haematopoietic stem-cell transplantation (HSCT) from partially compatible donors to adult patients with leukaemia and other high-risk haematologic malignancies. Zalmoxis is administered from the 21st day post-transplantation and foresees up to a maximum of 4 infusions per patient based on the achievement of immune-reconstitution.

The terms of the agreement provide for an ex-factory price, excluding VAT, of 149,000 EUR per infusion, gross of discounts foreseen by law and of selective reductions foreseen by AIFA Resolutions ("Determinazioni") of 3 July 2006 and 27 September 2006. Furthermore the agreement also set a flat fee per patient and a safeguard clause on sales for the first 24 months. Given the nature of the product, it will be a hospital-only dispensed therapy.

The agreement signed with AIFA will be effective from the fifteenth day subsequent to its publication in the Gazzetta Ufficiale of the Italian Republic.

Riccardo Palmisano, MolMed’s CEO, commented: "This is truly a turning point for a research and development company like MolMed: both Zalmoxis eligibility for reimbursement and the "Aifa granted price" acknowledge the value of our therapy and, at the same time, the successful completion of a top level Italian research, development and manufacturing journey. In addition, this result paves the way to the marketing of this sophisticated genetically engineered cell therapy. This first national authorization allows us to look with increasing confidence to the introduction of Zalmoxis in the other European countries covered by the Dompé agreement, from which we expect relevant results, considering our partner’s value, expertise and successful track record. Zalmoxis commercialization will allow MolMed to increase its revenues from proprietary products on top of those deriving from GMP development and production for third party."

Professor Claudio Bordignon, Founder and Chairman of MolMed, commented: "The inclusion of Zalmoxis among the medicinal products reimbursable by the National Health Service makes this revolutionary therapy available to those patients for whom the allogeneic stem cell transplantation is the best treatment option for high-risk leukaemia and other blood malignancies. In absence of a fully compatible donor, Zalmoxis makes the treatment from a haploidentical family donor safer, by eliminating post-transplant immunosuppression and, at the same time, resolving the potential occurrence of Graft versus Host Disease. Furthermore, Zalmoxis accelerates immune-reconstitution by protecting the patient against infections and leukaemia relapse. Zalmoxis has proven to significantly increase the one-year survival rate in the treated population."

"We are very pleased with the outcome of MolMed’s negotiation with AIFA. By stipulating this agreement, it is stated that Zalmoxis, the first ex-cell cellular therapy based on the immune system engineering for the PRESS RELEASE 2 treatment of adult patients with high risk blood malignancies, responds to a major clinical need", commented Eugenio Aringhieri, Chief Executive Officer of Dompé. "The synergy of our distinctive competences and shared value priorities, on which this alliance with MolMed is founded, will lead us in the interaction with the scientific community and the regulatory authorities aimed at bringing Zalmoxis to all Patients eligible for this therapy."

About Zalmoxis
Zalmoxis is an innovative therapy based on genetically engineering donor immune system T cells to carry an inducible "suicide gene". Administered to patients following HSCT from partially compatible donors (haploidentical HSCT), these cells foster an anti-leukaemia effect by eliminating post-transplant immunosuppression prophylaxis and inducing a rapid immune reconstitution. The suicide gene allows to readily control Graft versus Host Disease (GvHD), the most significant and serious adverse event in haploidentical transplantation, caused by the genetic disparity between patient and donor. Zalmoxis significantly increases long-term survival, regardless of disease status at transplant, thus making HSCT from partially compatible donors safer and more effective. On August 18th, 2016 the European Commission granted a Conditional Marketing Authorisation (CMA) for Zalmoxis, the first immunogene therapy, as patient-specific adjunctive treatment in haplo-identical haematopoietic stem-cell transplantation for adult patients with leukaemia and high-risk haematological malignancies. Following this authorization, which allows MolMed to market Zalmoxis in the 28 EU Member States and in the European Economic Area, activities aimed at its introduction on the European markets have increased. The marketing authorization issued by AIFA is therefore only the first out of the ones on which MolMed has been working since the date of the European CMA.

With the aim of successfully marketing Zalmoxis, on July 26th, 2017 MolMed signed an exclusive license and distribution agreement with Dompé Farmaceutici S.p.A., one of the leading Italian biopharmaceutical companies, granting Dompé the exclusive right and obligation to conduct all activities aimed at promoting, marketing, exploiting, distributing and selling Zalmoxis in all member countries of the current European Economic Area (EEA) and an option right for Switzerland, Turkey and Australia.

In parallel, preparation of the dossier to obtain price and reimbursement of Zalmoxis from the German and French authorities continued through direct interactions. Furthermore activities aimed at starting negotiations with authorities of other countries have been speeded up. In regard to distribution and marketing beyond the European borders, contracts have already been signed with Megapharm Ltd for Israel and with TTY Biopharm Company Ltd for Taiwan and a number of countries in South-East Asia.

On December 13, 2017 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo), reported results from the Hokusai-VTE CANCER study evaluating oral edoxaban (known by the brand names LIXIANA outside the U.S. and SAVAYSA in the U.S.), and found that edoxaban is non-inferior to subcutaneous injectable LMWH dalteparin for the treatment of cancer-associated VTE and major bleeding (Press release, Daiichi Sankyo, DEC 13, 2017, View Source [SID1234522607]). The results of the study were simultaneously published in the New England Journal of Medicine (NEJM) and presented during the late-breaker session at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Hokusai-VTE CANCER is the first study with a direct oral anticoagulant (DOAC), edoxaban, to meet pre-specified non-inferiority criteria versus the standard of care dalteparin in this patient population.2,3 The study met the primary objective of non-inferiority of edoxaban for the composite outcome of first recurrent VTE or ISTH-defined major bleeding during a 12-month study period, which occurred in 67 of 522 patients (12.8%) in the edoxaban group compared with 71 of 524 patients (13.5%) in the dalteparin group (hazard ratio with edoxaban, 0.97; 95% CI, 0.70 to 1.36; P = 0.006 for non-inferiority) for a risk difference (edoxaban minus dalteparin) of -0.7% (95% CI, -4.8 to 3.4).2,3 The difference in risk for recurrent VTE was -3.4% (95% CI, -7.0 to 0.2) whereas the corresponding difference in risk for major bleeding was 2.9% (95% CI, 0.1 to 5.6).3 The frequencies of severe major bleeding events at presentation (categories 3 and 4) were similar during treatment with edoxaban or dalteparin (12 patients in each group, respectively).2,3 There was no fatal bleed in the edoxaban group versus two fatal bleedings in the dalteparin arm.3

The study also met the secondary outcome of event-free survival (free of recurrent VTE, major bleeds or death) at 12 months, and rates were similar between edoxaban and dalteparin (55.0% and 56.5%, respectively).2,3 The trial was a PROBE design study and included a broad spectrum of patients (n=1,050) with primarily active cancer (98%): 53% of which had metastatic cancer and 72% of which were receiving cancer therapy at randomisation.2,3 This is the largest prospectively randomised clinical trial to have studied the benefit risk of DOACs in cancer patients versus the current injectable standard of care, dalteparin. Hokusai-VTE CANCER is the first study to demonstrate that a DOAC, edoxaban, is non-inferior to the standard of care, injectable LMWH (dalteparin), in this population.2,3

"Cancer patients have a significantly increased risk of VTE, and are a high-risk population since 82% of patients have one or more pre-specified bleeding risk factors," said co-principal study investigator Professor Harry Büller, from the Department of Vascular Medicine at Academic Medical Center, Amsterdam, The Netherlands. "We saw a lower rate of recurrent VTE with edoxaban compared to dalteparin over the one-year study period. In addition, in the edoxaban arm, we saw no bleeding fatalities and similar severity of clinical presentation of major bleeding events compared to dalteparin. The risk for VTE persists beyond six months for cancer patients, therefore, the study duration of 12 months enabled the evaluation of edoxaban over a longer time period."

VTE includes both deep vein thrombosis (DVT) and pulmonary embolism (PE) and is the second leading cause of death in cancer patients receiving chemotherapy.4 Current guidelines recommend LMWH for at least six months as the standard of care in cancer patients,5,6,7 and currently there is poor adherence to VTE cancer treatment guidelines due to the requirement for daily injections. The treatment of cancer-associated VTE is challenging because these patients are at increased risk of both recurrent VTE and major bleeding.2 The occurrence of VTE increases the risk of death 2-6-fold in cancer patients4 and can interrupt cancer treatment.8

"The use of an oral anticoagulant that alleviates the burdens associated with a daily injectable drug, without loss of clinical benefit, would represent an advance for cancer patients with VTE," said Hans J. Lanz, MD, Vice President, Global Medical Affairs, Daiichi Sankyo. "The data will continue to add to the growing body of knowledge in the Edoxaban Clinical Research Programme, which provides key insights into the potential effects of edoxaban in VTE and AF patients."

About the Hokusai-VTE CANCER study
Hokusai-VTE CANCER is a multinational, prospective, randomised, open-label, blinded endpoint evaluation (PROBE) study, evaluating the efficacy and safety of once-daily edoxaban compared to dalteparin for the treatment of VTE associated with cancer.1,2,3 The purpose of the study was to evaluate edoxaban in comparison with dalteparin in preventing the combined outcome of VTE recurrence or major bleeding in patients with VTE associated with cancer.1,2,3 Other objectives include assessing the effects of treatment on VTE recurrence, clinically relevant bleeding and event-free survival, defined as the proportion of subjects over time free of recurrent VTE, major bleeding events and death.1,2,3 The study enrolled 1,050 patients across 13 countries in North America, Europe, Australia and New Zealand.2,3 Patients were randomised to receive edoxaban 60 mg once-daily (reduced to 30 mg edoxaban for patients with creatinine clearance [CrCL] 30-50 mL/min, body weight ≤ 60 kg, or concomitant use of P-glycoprotein [P-gp] inhibitors), following treatment with LMWH for at least five days; or dalteparin SC 200 IU/kg once-daily for 30 days, then 150 IU/kg once-daily for the remainder of the 12-month study.1,2,3

For more information please visit: View Source

About Venous Thromboembolism
Venous thromboembolism (VTE) is an umbrella term for two conditions, deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a disease caused by a blood clot found in deep veins, usually within the lower leg, thigh or pelvis, although they can occur in other parts of the body as well.10 PE occurs when part of a clot detaches and lodges in the pulmonary arteries, causing a potentially fatal condition.11

About VTE and Cancer
VTE is a major cause of morbidity and mortality in patients with cancer, with an annual incidence that can be as high as 20 percent depending on the cancer type, background risk and time since diagnosis.12,13 Patients with cancer have multiple risk factors for VTE and the risk of VTE events increases in patients with cancer receiving chemotherapy.14 In addition, patients with cancer and VTE have a lower survival rate than those without VTE.14

About Edoxaban
Edoxaban is an oral, once-daily, direct factor Xa (pronounced "Ten A") inhibitor. Factor Xa is one of the key components responsible for blood clotting, so inhibiting this makes the blood thin and less prone to clotting. Edoxaban is currently marketed by Daiichi Sankyo and its partners in more than 20 countries around the world.

About Edoxaban Clinical Research Programme (ECRP)
Daiichi Sankyo is committed to expanding scientific knowledge about edoxaban, as demonstrated through our research programmes evaluating its use in a broad range of cardiovascular conditions, patient types and clinical settings in AF and VTE. The edoxaban clinical research programme includes multiple RCTs (randomised, controlled trials), registries and non-interventional studies, with the goal of generating new clinical and real-world-data regarding its use in AF and VTE populations. Daiichi Sankyo expects that more than 100,000 patients will participate in the edoxaban clinical research programme, including completed, ongoing, and future research.

The RCTs include:
− ENSURE-AF (EdoxabaN vs. warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation), in AF patients undergoing electrical cardioversion
− ENTRUST-AF PCI (EdoxabaN TReatment versUS VKA in paTients with AF undergoing PCI), in AF patients undergoing percutaneous coronary intervention
− Hokusai-VTE CANCER (Edoxaban in Venous Thromboembolism Associated with Cancer), in patients with cancer and an acute VTE event
− ELDERCARE-AF (Edoxaban Low-Dose for EldeR CARE AF patients), in elderly AF patients in Japan
− ELIMINATE-AF (EvaLuatIon of edoxaban coMpared with VKA IN subjects undergoing cAThEter ablation of non-valvular Atrial Fibrillation)
− ENVISAGE-TAVI AF (EdoxabaN Versus standard of care and theIr effectS on clinical outcomes in pAtients havinG undergonE Transcatheter Aortic Valve Implantation (TAVI) – Atrial Fibrillation)

In addition, global and regional registry studies will provide important real-world data about the use of edoxaban and other oral anticoagulants in everyday practice, and include:
− ETNA-AF (Edoxaban Treatment in routiNe clinical prActice in patients with non valvular Atrial Fibrillation)
− ETNA-VTE (Edoxaban Treatment in routiNe clinical prActice in patients with Venous ThromboEmbolism)
− EMIT-AF/VTE (Edoxaban Management In diagnostic and Therapeutic procedures-AF/VTE);
− Prolongation PREFER in AF (PREvention oF thromboembolic events – European Registry) in patients with AF
− ANAFIE (All Nippon AF In Elderly) Registry in Japan
− Cancer-VTE Registry in Japan

We are committed to adding to the scientific body of knowledge around edoxaban in a variety of AF and VTE patients, including those who are vulnerable.

On December 13, 2017 Bristol-Myers Squibb Company (NYSE: BMY) reported that the U.S. Food and Drug Administration (FDA) has accepted its supplemental Biologics License Application (sBLA) for priority review of Opdivo (nivolumab) plus Yervoy (ipilimumab) to treat intermediate- and poor-risk patients with advanced renal cell carcinoma (RCC) (Press release, Bristol-Myers Squibb, DEC 13, 2017, View Source [SID1234522638]). The FDA also previously granted Breakthrough Therapy Designation for this application, which is the 2nd indication for which the Opdivo plus Yervoy combination has received this designation.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"At BMS, we hope to provide treatment options to patients with advanced forms of renal cell carcinoma," said Murdo Gordon, executive vice president and chief commercial officer, Bristol-Myers Squibb. "Breakthrough therapy designation and today’s filing acceptance for the Opdivo plus Yervoy combination are an important step in our ongoing efforts to advance therapies to address a high unmet need in first-line treatment of kidney cancer in intermediate- and poor-risk patients."

The application is based on data from the phase 3 CheckMate -214 study, which was stopped early based on the recommendation of an independent Data Monitoring Committee following a planned interim analysis of overall survival. The results of the study were recently presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress.

The Breakthrough Therapy Designation is an FDA program intended to expedite the development and review of medicines with signals of potential clinical benefit in serious diseases to help ensure patients have access to new therapies as soon as possible.

The application has an action date of April 16, 2018.

About CheckMate -214
CheckMate -214 is a phase 3, randomized, open-label study evaluating the combination of Opdivo plus Yervoy versus sunitinib in patients with previously untreated advanced or metastatic renal cell carcinoma. Patients in the combination group received Opdivo 3 mg/kg plus Yervoy 1 mg/kg every 3 weeks for 4 doses followed by Opdivo 3 mg/kg every 2 weeks. Patients in the comparator group received sunitinib 50 mg once daily for 4 weeks, followed by 2 weeks off before continuation of treatment. Patients were treated until progression or unacceptable toxic effects. The primary endpoints of the trial are overall survival, progression-free survival and objective response rate in an intermediate to poor-risk patient population (approximately 75% of patients). Safety is a secondary endpoint. The study met the co-primary endpoints of improved overall survival and objective response rate compared to sunitinib in intermediate- and poor-risk patients. While the combination demonstrated an improvement in progression-free survival relative to sunitinib, another co-primary endpoint, it did not reach statistical significance.

Adverse events (AEs) leading to discontinuation were reported in 22% of patients (547) in the combination group, compared with 12% of patients in the sunitinib group (535). The most common grade 3/4 AEs in the combination group were fatigue (4%), diarrhea (4%), rash (2%), nausea (2%), and, in less than 1% each, pruritus, hypothyroidism, vomiting and hypertension. In the sunitinib group, the most common grade 3/4 AEs were hypertension (16%), fatigue (9%), Palmar-plantar erythrodysaesthesia syndrome (9%), stomatitis (3%), mucosal inflammation (3%), vomiting (2%), nausea (1%), decreased appetite (1%), hypothyroidism (<1%) and dysgeusia (<1%). There were seven treatment-related deaths in the combination group and four in the sunitinib group.

About Renal Cell Carcinoma
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, accounting for more than 100,000 deaths worldwide each year. Clear-cell RCC is the most prevalent type of RCC and constitutes 80% to 90% of all patients. RCC is approximately twice as common in men as in women, with the highest rates of the disease in North America and Europe. Globally, the five-year survival rate for those diagnosed with metastatic, or advanced, kidney cancer is 12.1%.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
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 for hard-to-treat cancers that could potentially improve outcomes for these patients.

We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O radiation therapies across multiple tumors and potentially deliver the next wave of therapies 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 how patients’ tumor biology can be used as a guide for treatment decisions throughout their journey.

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 60 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 50 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 adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. 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.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

U.S. FDA-APPROVED INDICATIONS FOR YERVOY

YERVOY (ipilimumab) is indicated for the treatment of unresectable or metastatic melanoma in adults and pediatric patients (12 years and older).

YERVOY (ipilimumab) is indicated for the adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.

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 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).

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. For patients without HCC, withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4. For patients with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT is within normal limits at baseline and increases to >3 and up to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and up to 3 times ULN at baseline and increases to >5 and up to 10 times the ULN, and if AST/ALT is >3 and up to 5 times ULN at baseline and increases to >8 and up to 10 times the ULN. Permanently discontinue OPDIVO and administer corticosteroids if AST or ALT increases to >10 times the ULN or total bilirubin increases >3 times the ULN. 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 Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients receiving OPDIVO.

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 the adverse reaction, permanently discontinue or withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy. Across clinical trials of OPDIVO monotherapy or in combination with YERVOY, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in <1.0% of patients receiving OPDIVO: myocarditis, rhabdomyolysis, myositis, 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), 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, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in ≥1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO. The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in at least 2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 040, serious adverse reactions occurred in 49% of patients (n=154). The most frequent serious adverse reactions reported in at least 2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, and pneumonia.

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, the most common adverse reactions (≥20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (≥10%) in patients receiving OPDIVO were cough and dyspnea at a higher incidence than investigator’s choice. In Checkmate 275, the most common adverse reactions (≥ 20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 040, the most common adverse reactions (≥20%) in patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). The most common adverse reactions (≥20%) in patients who received OPDIVO as a single agent were fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory tract infection, and pyrexia.

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%).

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

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; Checkmate 141 – squamous cell carcinoma of the head and neck; Checkmate 275 – urothelial carcinoma; Checkmate 040 – hepatocellular carcinoma.

About the Bristol-Myers Squibb and Ono Pharmaceutical Co., Ltd. Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Ltd (Ono), Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

On December 13, 2017 Pionyr Immunotherapeutics, Inc., a company developing antibody therapeutics that increase the body’s antitumor immunity by rebalancing the myeloid infiltrate in the tumor microenvironment, reported the closing of a $62 million Series B investment round. This brings total funding since the company’s founding in 2015 to $72 million. The Series B financing was led by New Enterprise Associates and included Sofinnova Ventures and Vida Ventures, along with Pionyr’s existing investors, OrbiMed, SV Health Investors, Osage University Partners, and Mission Bay Ventures.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Research conducted at Pionyr over the past year shows that its most advanced technology, Myeloid Tuning, is capable of rebalancing the tumor microenvironment to favor immune-activating myeloid cells over immune-suppressing myeloid cells. This activity is believed to enhance antitumor efficacy, particularly in combination with checkpoint inhibition. The proportions of specific subpopulations of myeloid cells in the tumor microenvironment have been shown to correlate with clinical outcome and predict checkpoint inhibitor responsiveness.

"Our technology has led to a promising pipeline of potential new therapeutics against novel and highly specific targets in the tumor microenvironment," Max Krummel, Ph.D., UC San Francisco professor, Pionyr co-founder and member of the board of directors said. "We believe these drug candidates hold the keys to an untapped area of immuno-oncology and may have a significant impact on multiple cancers."

Dr. Krummel has been a pioneer in immuno-oncology since the mid-1990s and is the co-inventor of YERVOY (ipilimumab), the first marketed checkpoint inhibitor, which was approved in 2011 to treat melanoma.

Pionyr was co-founded by Dr. Krummel and Sachdev Sidhu, Ph.D., a protein engineer and key player in early antibody phage-display technology platforms, formerly at Genentech, who is now head of protein engineering and antibody discovery at the University of Toronto.

Pionyr is led by industry veterans with deep biotech management experience and immuno-oncology expertise. Steven James, former CEO of Labrys Biologics (acquired by TEVA) and KAI Pharmaceuticals (acquired by Amgen), is the president and CEO of the company. The company’s senior vice president of research is Michel Streuli, Ph.D., who has over 15 years of pharma and biotech experience, and previously led immuno-oncology efforts at Gilead, Merck (as early development head for KEYTRUDA), Schering-Plough, and Organon.

"Pionyr has made great progress over the past year and we are extremely gratified that this has led to a financing sufficient in size to take two of our antibodies into human cancer trials," James said. "NEA, Sofinnova Ventures, and Vida Ventures are superb additions to our existing syndicate of top flight investors, and have been tremendously supportive of our efforts to push forward with multiple programs emerging from our pipeline."

Joining Prof. Krummel, Mr. James, Leon Chen, Ph.D. (OrbiMed Advisors), and Joshua Resnick, M.D. (SV Health Investors) on the Pionyr board of directors are Carol Gallagher, Pharm.D. (NEA), Mike Powell, Ph.D. (Sofinnova) and Arjun Goyal, M.D. (Vida Ventures) as an observer.

Dr. Carol Gallagher commented, "We are impressed with the rapid translation work the Pionyr team has conducted and look forward to working with them to enable these novel drug candidates to advance toward the clinic to evaluate the promise of this novel approach in immuno-oncology."

On December 13, 2017 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported updates related to its collaboration programs with Sanofi, which were highlighted during Sanofi’s Sustaining Innovation Analyst Day in Paris, France (Press release, Regeneron, DEC 13, 2017, View Source [SID1234522610]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In a separate release today the companies also shared positive topline results for PD-1 antibody cemiplimab in advanced cutaneous squamous cell carcinoma (CSCC).

Immunology and Inflammation: Dupixent (dupilumab) and IL-33 antibody

A supplemental Biologics License Application (sBLA) for dupilumab in persistent, uncontrolled asthma is expected to be submitted in the fourth quarter of 2017.
In 2018, a Dupixent (dupilumab) sBLA submission is planned for atopic dermatitis in adolescents ages 12 to 17, and in 2019, a second sBLA is planned for children ages 6 to 12.
In 2019, an sBLA is planned for dupilumab in adults with nasal polyposis.
Pivotal Phase 3 studies are planned for 2018 evaluating the use of dupilumab in chronic obstructive pulmonary disease (COPD), a condition for which there are no approved biologic therapies.
A pivotal Phase 3 study is planned for 2018 evaluating the use of dupilumab in eosinophilic esophagitis (EoE), a condition for which there are no approved therapies in the U.S.
Phase 2 studies investigating the use of dupilumab as an adjunctive therapy to immunotherapies for the treatment of peanut and grass allergy are planned for 2018.
Dupilumab studies are planned for 2018 to evaluate patients with comorbid allergic inflammatory conditions.
REGN3500, an antibody to IL-33, is currently being investigated in Phase 1b studies in adult patients with moderate asthma and mild allergic asthma both as monotherapy and in combination with dupilumab.
In 2018, the companies plan to initiate Phase 2 proof-of-concept studies for REGN3500 in asthma and COPD, and a Phase 2b study in atopic dermatitis.
Immunology and Inflammation: Kevzara (sarilumab)

Phase 3 studies of sarilumab in giant cell arteritis and polymyalgia rheumatica are expected to be initiated in 2018.
A Phase 2 study of sarilumab in systemic juvenile arthritis is also expected to begin in 2018.
Immuno-Oncology

In the first quarter of 2018, the companies plan to submit a BLA to the FDA for cemiplimab (REGN2810, PD-1 antibody) for the lead indication of locally advanced and unresectable or metastatic CSCC.
Further development plans for cemiplimab include ongoing studies in basal cell carcinoma and cervical cancer.
Three Phase 3 studies are either planned or underway in first-line non-small cell lung cancer (NSCLC):
Cemiplimab vs. platinum doublet in patients with PD-L1 expression greater than or equal to 50 percent (ongoing).
Cemiplimab in combination with ipilimumab or chemotherapy vs. platinum doublet in patients with PD-L1 expression less than 50 percent (initiated).
Cemiplimab in combination with ipilimumab or chemotherapy in patients with PD-L1 expression greater than or equal to 50 percent (planned).
A second-line study of cemiplimab in NSCLC is also planned.
Regeneron is also advancing REGN3767, a LAG3 antibody, for cancer both as monotherapy and in combination with cemiplimab, as well as other preclinical immuno-oncology bispecific and monoclonal antibody therapies.
Cardiovascular Disease: Praluent (alirocumab)

Data from the ODYSSEY OUTCOMES trial evaluating PRALUENT (alirocumab) are expected in the first quarter of 2018.
The median duration of treatment in the ODYSSEY OUTCOMES study is 33 months, with some patients treated for up to five years.
Based on data from ODYSSEY OUTCOMES, the companies anticipate submitting an sBLA to the FDA by the third quarter of 2018. (Press release, Regeneron, DEC 13, 2017, View Source [SID1234522610])