European Medicines Agency’s CHMP Recommends Approval for Merck’s KEYTRUDA® (pembrolizumab) for the Treatment of Certain Patients with Locally Advanced or Metastatic Urothelial Carcinoma, a Type of Bladder Cancer
European Medicines Agency’s CHMP Recommends Approval for Merck’s KEYTRUDA® (pembrolizumab) for the Treatment of Certain Patients with Locally Advanced or Metastatic Urothelial Carcinoma, a Type of Bladder CancerRecommendation is for Treatment in Adult Patients Who Have Received Prior Platinum- Containing Chemotherapy and for Adult Patients Who Are Not Eligible for Cisplatin-Containing ChemotherapyPositive Opinion is Based on Overall Survival Benefit Demonstrated in the Phase 3 KEYNOTE-045 Trial and Durable Responses Observed in the Phase 2 KEYNOTE-052 TrialJuly 21, 2017 07:31 AM Eastern Daylight Time KENILWORTH, N.J.--(EON: Enhanced Online News)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of certain patients with locally advanced or metastatic urothelial carcinoma, a type of bladder cancer. Specifically, KEYTRUDA is recommended for the treatment of locally advanced or metastatic urothelial carcinoma in adult patients who have received prior platinum-containing chemotherapy, as well as adult patients who are not eligible for cisplatin-containing chemotherapy. The recommendation will now be reviewed by the European Commission for marketing authorization in the European Union. A final decision is expected in the third quarter of 2017.“We are pleased that the CHMP has provided a positive opinion for KEYTRUDA in these two patient populations and look forward to working with the European Commission to bring forward this new option for patients in need.” “There is significant need for new options that address the treatment gaps for patients in Europe with locally advanced or metastatic urothelial carcinoma, especially for those who have failed on prior platinum treatment or are ineligible for cisplatin-containing chemotherapy,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “We are pleased that the CHMP has provided a positive opinion for KEYTRUDA in these two patient populations and look forward to working with the European Commission to bring forward this new option for patients in need.”The positive opinion is based on data from the KEYNOTE-045 and KEYNOTE-052 trials. KEYNOTE-045 is a phase 3, randomized study investigating KEYTRUDA (pembrolizumab) compared to investigator-choice chemotherapy (paclitaxel, docetaxel, vinflunine) in patients with locally advanced or metastatic urothelial carcinoma that has recurred or progressed on or after platinum-containing chemotherapy. KEYNOTE-052 is a phase 2, open-label study investigating KEYTRUDA in treatment-naïve patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing therapy.The KEYTRUDA clinical development program includes more than 30 tumor types in more than 500 clinical trials, including more than 300 trials that combine KEYTRUDA with other cancer treatments. Currently, Merck has the largest immuno-oncology clinical development program in bladder cancer, with 29 trials underway involving KEYTRUDA as monotherapy and in combination, including four registration-enabling studies.About Bladder CancerBladder cancer begins when cells in the urinary bladder start to grow uncontrollably. As more cancer cells develop, they can form a tumor and spread to other areas of the body. Urothelial carcinoma, the most common type of bladder cancer, starts in the urothelial cells that line the inside of the bladder. In 2012, approximately 430,000 people worldwide were diagnosed with bladder cancer and 165,000 died from the disease. The incidence of bladder cancer is elevated in North America, Europe, North Africa, the Middle East, Australia and New Zealand.About KEYTRUDA® (pembrolizumab) InjectionKEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.Studies of KEYTRUDA – from the largest immuno-oncology program in the industry with more than 500 trials – include a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand factors that predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including the exploration of several different biomarkers across a broad range of tumors.KEYTRUDA (pembrolizumab) is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single-dose vial in the U.S.KEYTRUDA (pembrolizumab) Indications and Dosing in the U.S.MelanomaKEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.Lung CancerKEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.KEYTRUDA, as a single agent, is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin.Head and Neck CancerKEYTRUDA (pembrolizumab) is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. 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. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.Classical Hodgkin LymphomaKEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. 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. In adults with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.Urothelial CarcinomaKEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-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 the confirmatory trials.KEYTRUDA is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.In locally advanced or metastatic urothelial carcinoma, KEYTRUDA (pembrolizumab) is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.Microsatellite Instability-High (MSI-H) CancerKEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan. 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. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with MSI-H cancer, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.Selected Important Safety Information for KEYTRUDA® (pembrolizumab)KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.KEYTRUDA (pembrolizumab) can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.KEYTRUDA (pembrolizumab) can cause other clinically important immune-mediated adverse reactions. These immune-mediated reactions may occur in any organ system. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.Solid organ transplant rejection has been reported in postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment with KEYTRUDA vs the risk of possible organ rejection in these patients.KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after treatment with KEYTRUDA on any trial, 6 patients (26%) developed graft-versus-host-disease (GVHD), one of which was fatal, and 2 patients (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, one of which was fatal. Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor–blocking antibody before transplantation. 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.Based on its mechanism of action, KEYTRUDA (pembrolizumab) can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reactions (in≥20% of patients) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%). Eighteen patients (5%) died from causes other than disease progression. Five patients (1.4%) who were treated with KEYTRUDA experienced sepsis which led to death, and 3 patients (0.8%) experienced pneumonia which led to death. Adverse reactions leading to interruption of KEYTRUDA occurred in 22% of patients; the most common (≥1%) were liver enzyme increase, diarrhea, urinary tract infection, acute kidney injury, fatigue, joint pain, and pneumonia. Serious adverse reactions occurred in 42% of patients, the most frequent (≥2%) of which were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Adverse reactions leading to interruption of KEYTRUDA occurred in 20% of patients; the most common (≥1%) were urinary tract infection (1.5%), diarrhea (1.5%), and colitis (1.1%). The most common adverse reactions (20%) in patients who received KEYTRUDA vs those who received chemotherapy were fatigue (38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs 13%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients, the most frequent (≥2%) of which were urinary tract infection, pneumonia, anemia, and pneumonitis.It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.Our Focus on CancerOur goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 500 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
Ipsen Receives Positive CHMP Opinion for Approval of Xermelo® (Telotristat Ethyl), for the Treatment of Carcinoid Syndrome Diarrhea in Patients Inadequately Controlled by Somatostatin Analogue Therapy
psen (Euronext: IPN; ADR: IPSEY) today announced that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has adopted a positive opinion recommending the approval of Xermelo® (telotristat ethyl) 250 mg three times a day (tid) for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analogue (SSA) therapy in adults inadequately controlled by SSA therapy. The CHMP positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the 28 countries of the European Union, as well as Norway, Liechtenstein and Iceland.David Meek, Chief Executive Officer of Ipsen, said: “The positive CHMP opinion for Xermelo® is an important milestone towards providing innovative solutions along every step of the treatment pathway for neuroendocrine tumors. Xermelo® is a novel treatment option and is the first oral tryptophan hydroxylase inhibitor, studied in combination with a somatostatin analog to demonstrate significant relief to patients and can contribute to an improved quality of life. We are very pleased to move closer to providing a new treatment option for European patients suffering from this debilitating condition.”“The medical community is very pleased to have Xermelo® as a new therapeutic option for patients with carcinoid syndrome”, said Professor Juan Valle, University of Manchester and The Christie in Manchester, UK. He added “The positive safety and efficacy data of telotristat ethyl has meant that it has already been integrated in the majority of international guidelines including ENETS1 guidelines reflecting the high level of unmet need in this condition”.The detailed recommendations for the use of this product will be described in the Summary of Product Characteristics (SmPC), to be made available once the medication receives marketing authorization from the European Commission.About the TELESTAR Phase 3 Pivotal Trial The efficacy and safety of telotristat ethyl 250 mg taken tid were established in a 12-week double-blind, placebo-controlled, randomised, multicentre phase 3 trial. The study included a 36-week open-label extension period during which all patients were treated with a higher dose of telotristat ethyl. A total of 135 patients were recruited in 12 countries (AU, BE, CA, FR, DE, IL, IT, NL, ES, SE, UK, USA). The mean age was 64 years (range 37 to 88 years) and 52% were male. All patients had a well-differentiated metastatic neuroendocrine tumours with documented history of carcinoid syndrome, and were treated with stable-dose SSAs for ≥ 3 months before enrolment. Patients had an average of four or more bowel movements (BM) per day: at baseline, mean daily BM frequency averaged over the baseline period were 5.2 and 6.1 counts/day in the placebo and telotristat ethyl 250 mg groups, respectively. The study included a 12-week double-blind treatment (DBT) period, in which patients initially received placebo (n=45) or telotristat ethyl 250 mg (n=45) or a higher dose (telotristat ethyl 500 mg; n=45) three times daily. During the study, patients were allowed to use rescue medication (short-acting SSA therapy) and anti-diarrheals for symptomatic relief but were required to be on stable-dose of long-acting SSA therapy for the duration of the DBT period.The primary endpoint was the mean change from baseline in daily BM frequency averaged over the 12-week double blind period. Estimated difference in BM frequency per day versus placebo averaged over 12 weeks was -0.81 for telotristat ethyl 250mg (p<0.001).A substantially greater proportion of patients on telotristat ethyl 250 mg tid achieved a durable response, defined as at least a 30 percent reduction in daily bowel movements over at least half the days of the 12-week DBT period: 44 percent on telotristat ethyl, as compared to 20 percent on placebo (p<0.040). When the full effect of telotristat ethyl is observed (during the last 6 weeks of the DBT period) the proportion of responders with at least 30% BM reduction was 51% (23/45) in the 250 mg group versus 22% (10/45) in the placebo group (post-hoc analysis).Telotristat ethyl significantly reduced the percent change from baseline in urinary 5-hydroxyindole acetic acid (u-5HIAA) versus placebo at week 12 (p< 0.001).About the TELECAST Phase 3 Trial The Phase 3 TELECAST study was designed similarly to TELESTAR study as a companion to this pivotal Phase 3 study to provide additional efficacy and safety information in patients with carcinoid syndrome. A total of 76 patients were evaluated for efficacy. The mean age was 63 years (range 35 to 84 years) and 55% were male. All patients had well-differentiated metastatic neuroendocrine tumour with carcinoid syndrome. Most patients (92.1%) had fewer than 4 BM per day and all except 9 were treated by SSA therapy.The primary endpoints were the percent change from Baseline in u5-HIAA at Week 12 and incidence of treatment emergent adverse events (TEAEs). The mean u5-HIAA excretion at baseline was 69.1 mg/24hours in the telotristat ethyl 250 mg tid group (n=17) and 84.8 mg/24hours in the placebo group (n=22). The percent change from baseline in u5-HIAA excretion at week 12 was +97.7% in the placebo group versus -33.2% in the telotristat ethyl 250 mg tid group.Notably, 40% of patients in the telotristat ethyl 250 mg tid treatment arm achieved a ≥30% reduction in BM frequency for at least 50% of the days in the double-blind treatment period, while there were no responders in the placebo arm (p=0.001).General safety information about Xermelo® In clinical trials, over 230 patients with carcinoid syndrome were treated with Xermelo®. The placebo-controlled safety analyses were focused on the integrated data from the 12-week placebo-controlled double-blind periods from the two phase 3 randomized clinical trials. For this safety analysis, 71 patients received placebo and 70 patients received Xermelo® 250 mg three times daily. The most commonly reported adverse reactions in patients treated with telotristat ethyl were abdominal pain (26%), gamma-glutamyl transferase increased (11%) and fatigue (10%). They were generally of mild or moderate intensity. The most frequently reported adverse reaction leading to discontinuation of telotristat ethyl was abdominal pain in 7.1% of patients (5/70).About carcinoid syndrome (CS) Well-differentiated neuroendocrine tumor (NET) is a relatively rare tumor type that arises from cells of the neuroendocrine system. Carcinoid syndrome (CS) occurs when well-differentiated NETs secrete large amounts of serotonin and other vasoactive products into the systemic circulation. Classically, symptoms associated with CS include cutaneous flushing, diarrhea, wheezing, abdominal pain, and in the long-term, valvular heart disease.Somatostatin analogues (SSA) are the cornerstone of therapy for the relief of CS and tumor control. SSA inhibit the release of serotonin by NETs and have become first-line therapy for CS. Due to the severe morbidity of CS and the lack of established treatment options, the population of patients with CS needing further control in addition to their SSA therapy is one with a high unmet medical need.About Xermelo® (telotristat ethyl) Xermelo® is a novel, orally administered, inhibitor of the enzyme tryptophan hydroxylase (TPH). Through inhibition of TPH, the rate-limiting step in the synthesis of serotonin, Xermelo® was designed to reduce the production of serotonin within neuroendocrine tumors.On 22 October 2014, Ipsen and Lexicon announced that they had entered into an exclusive licensing agreement for Ipsen to commercialize Xermelo® (telotristat ethyl) in all territories excluding the United States and Japan, where Lexicon retains the rights. On 28 February 2017, Lexicon received U.S. Food and Drug Administration (FDA) approval for Xermelo® as a first and only orally administered therapy for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy.About Ipsen Ipsen is a global specialty-driven biopharmaceutical group focused on innovation and specialty care. The group develops and commercializes innovative medicines in three key therapeutic areas - Oncology, Neurosciences and Rare Diseases. Its commitment to oncology is exemplified through its growing portfolio of key therapies for prostate cancer, neuroendocrine tumors, renal cell carcinoma and pancreatic cancer. Ipsen also has a well-established Consumer Healthcare business. With total sales close to €1.6 billion in 2016, Ipsen sells more than 20 drugs in over 115 countries, with a direct commercial presence in more than 30 countries. Ipsen's R&D is focused on its innovative and differentiated technological platforms located in the heart of the leading biotechnological and life sciences hubs (Paris-Saclay, France; Oxford, UK; Cambridge, US). The Group has about 5,100 employees worldwide. Ipsen is listed in Paris (Euronext: IPN) and in the United States through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information on Ipsen, visit www.ipsen.com.
Preclinical Study Using Parsortix Presented at Tumor Models Boston Summit
GUILDFORD, England--(EON: Enhanced Online News)--ANGLE plc (AIM: AGL OTCQX: ANPCY), a world-leading liquid biopsy company, today announced the presentation of independent study data by Western University on circulating tumor cell (CTC) analysis in preclinical models of cancer metastasis at the Tumor Models Summit in Boston on Thursday, July 20.“Of the three types of liquid biopsy technology employed in cancer management, the analysis of CTCs is the most advanced and could potentially revolutionize the treatment of cancer patients” The study will be presented by Alison Allan, Ph.D., Associate Professor, Departments of Anatomy & Cell Biology & Oncology Schulich School of Medicine and Dentistry, Western University based in Toronto, Canada.The study findings demonstrate the potential use of clinically-relevant CTC technologies such as ANGLE’s proprietary Parsortix™ platform to enhance the translation of cancer biology and highlight the importance of developing cancer drugs using metastasis models, rather than just primary tumor pre-clinical models.Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. To reduce the incidence of metastatic disease, drug development should target the metastatic process itself, which is the cause of over 90 percent of cancer deaths. In particular, the use of clinically-relevant CTC technologies such as the Parsortix system will enhance the translation of cancer biology and new cancer therapies from animal models to clinical trials.In the study, Dr. Allan used three approaches – Flow Cytometry, CellSearch®, and Parsortix – to capture and isolate CTCs of mouse models with breast and prostate cancer. In vivo data showed that Parsortix is best suited for this work for multiple reasons including its ability to analyze CTC clusters (which have been shown to be associated with aggressive disease) as well as the option to isolate and recover cells for further analysis. The Parsortix system’s epitope-independence (capturing all types of CTCs) and its automated ease of use are also highlighted.“Of the three types of liquid biopsy technology employed in cancer management, the analysis of CTCs is the most advanced and could potentially revolutionize the treatment of cancer patients,” said Dr. Allan. “The presence of CTCs can be detected early in the course of a cancer and is a fundamental prerequisite of metastasis. Their identification offers great potential not only in the diagnosis of patients but also in assessing their progression and likely outcome. When comparing the three methods used, ANGLE’s Parsortix system proved to be the most advanced in its ability to harvest viable cells for downstream analysis, which is critical to research and patient care.”“The findings from Dr. Allan’s study show that ANGLE’s Parsortix system continues to be evaluated positively when compared to other CTC technologies, and has demonstrated pre-clinical utility as well as the potential for clinical utility. A key advantage that Parsortix now offers, which is not available with most other approaches, is a low volume adaptor to enable the processing of small volumes of mouse blood,” said Peggy Robinson, Vice President, ANGLE North America, Inc.The results of the study demonstrate the utility of CTCs in pre-clinical tumor models. CTCs enable the monitoring of early dissemination and kinetics of the metastatic process in real-time and may lead to an increased understanding of metastatic biology. Further, it could accelerate innovation in metastasis-specific drug development and allow for timely assessment of a patient’s response to a therapy.Western University is a customer of ANGLE and its research work is independent of the Company.For more information about the conference, including the full agenda, visit http://tumor-models.com/.About ANGLE plcANGLE is a world-leading liquid biopsy company commercialising a disruptive platform technology that can capture cells circulating in blood, such as cancer cells, even when they are as rare in number as one cell in one billion blood cells, and harvest the cells for analysis.ANGLE’s cell separation technology is called the Parsortix™ system and it enables a liquid biopsy (simple blood test) to be used to provide the cells of interest. Parsortix is the subject of granted patents in Europe, the United States, Canada, China, Japan and Australia and three extensive families of patents are being progressed worldwide. The system is based on a microfluidic device that captures live cells based on a combination of their size and compressibility. Parsortix has a CE Mark for Europe and FDA authorisation is in process for the United States.ANGLE has established formal collaborations with world-class cancer centres. These Key Opinion Leaders are working to identify applications with medical utility (clear benefit to patients), and to secure clinical data that demonstrates that utility in patient studies. Details are available here http://www.angleplc.com/the-company/collaborators/The analysis of the cells that can be harvested from patient blood with ANGLE’s Parsortix system has the potential to help deliver personalised cancer care offering profound improvements in clinical and health economic outcomes in the treatment and diagnosis of various forms of cancer.The global increase in cancer to a 1 in 3 lifetime incidence is set to drive a multi-billion dollar clinical market. The Parsortix system is designed to be compatible with existing major medtech analytical platforms and to act as a companion diagnostic for major pharma in helping to identify patients that will benefit from a particular drug and then monitoring the drug’s effectiveness.As well as cancer, the Parsortix technology has the potential for deployment with several other important cell types in the future.ANGLE stock trades on the AIM market of the London Stock Exchange under the ticker symbol AGL and in New York on the OTC-QX under the ticker symbol ANPCY. For further information please visit: www.angleplc.comContactsANGLE plc, +44 1483 343434 Andrew Newland, Chief Executive Ian Griffiths, Finance Director or Cenkos Securities, +44 20 7397 8900 Stephen Keys (Nominated adviser), Steve Cox Russell Kerr (Sales) or WG Partners, +44 20 3705 9330 David Wilson Claes Spång or FTI Consulting Simon Conway, Mo Noonan, Stephanie Cuthbert, +44 20 3727 1000 Kimberley Ha (US), +1 212 850 5612
Philogen Enters into Multi-Target Research Agreement with Boehringer Ingelheim in the Field Of DNA-Encoded Chemistry
IENA, Italy--(EON: Enhanced Online News)--Philogen S.p.A., a privately owned biotechnology company today announced a collaboration and license agreement with Boehringer Ingelheim to discover and optimize novel small molecule-based therapeutics using Philochem’s proprietary Encoded Self-Assembling Chemical (ESAC) Library Technology platform.“We are very excited about the opportunity to apply Philochem’s DNA-encoded library technology to drugging intractable proteins. We believe that Philochem’s unique chemistry combined with Boehringer Ingelheim’s capabilities in discovering novel drugs could accelerate the optimization of chemical starting points to potent drug candidates” “We are extremely pleased to announce a new collaboration with Boehringer Ingelheim, a very innovative pharmaceutical company with a long tradition both in the field of therapeutic proteins and of small-molecule pharmaceuticals. After the initial clinical collaboration with Boehringer Ingelheim in the immune-oncology space announced in 2016, this second partnership underlines the good relationship between the two companies. We are both committed to the creation of new pharmaceutical agents, which may help treat serious unmet medical needs and provide a benefit to patients. ESAC technology is ideally suited for the identification of synergistic chemical fragments, which recognize adjacent binding sites on the surface of the target protein of interest. We are confident that ESAC technology will facilitate hit and lead discovery activities, complementing the strong Medicinal Chemistry technologies already established at Boehringer Ingelheim”, commented Prof. Dario Neri, co-founder and President of the Scientific Advisory Board of Philogen.ESAC technology represents an innovative proprietary methodology for the construction and screening of DNA-encoded chemical libraries of unprecedented size and quality. ESAC libraries, which are generated by the combinatorial self-assembly of encoded libraries of very high purity, are different compared to conventional single-pharmacophore chemical libraries.Darryl McConnell, Vice President and Head, Boehringer Ingelheim Research Site Austria, said, “We are very excited about the opportunity to apply Philochem’s DNA-encoded library technology to drugging intractable proteins. We believe that Philochem’s unique chemistry combined with Boehringer Ingelheim’s capabilities in discovering novel drugs could accelerate the optimization of chemical starting points to potent drug candidates”.No financial details of the agreement were released.About the Philogen groupPhilogen is a Swiss-Italian clinical-stage company engaged in the discovery and development of novel pharmaceutical and biopharmaceutical products. Philogen’s strategy is to deliver bioactive agents, for example cytokines or drugs, to the site of disease using antibodies and other ligands that specifically and efficiently target stromal antigens. This technology has generated a strong proprietary pipeline of clinical-stage products and also pre-clinical compounds in an array of disease indications. Philogen is headquartered in Siena, Italy, and has research activities at its subsidiary company Philochem in Zürich, Switzerland. Philogen is independently owned, and has signed agreements with several major pharmaceutical companies. For more information please visit www.philogen.com.About Philochem’s ESAC platform and DNA-Encoded Chemistry technologyThe proprietary ESAC platform and DNA-Encoded Chemistry technology were developed by Philochem scientists in collaboration with the group of Prof. Dario Neri at ETH Zurich during the past decade. These two powerful and complementary discovery technologies allow to screen up to billions small molecules and to further optimize the hit compounds in a fully automatic, DNA-tagged, fragment-based drug discovery manner.ContactsPhilogen Monica Patti email@example.com
The U.S. Food and Drug Administration today approved Vosevi to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis. Vosevi is a fixed-dose, combination tablet containing two previously approved drugs – sofosbuvir and velpatasvir – and a new drug, voxilaprevir. Vosevi is the first treatment approved for patients who have been previously treated with the direct-acting antiviral drug sofosbuvir or other drugs for HCV that inhibit a protein called NS5A. “Direct-acting antiviral drugs prevent the virus from multiplying and often cure HCV. Vosevi provides a treatment option for some patients who were not successfully treated with other HCV drugs in the past,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research.Hepatitis C is a viral disease that causes inflammation of the liver that can lead to diminished liver function or liver failure. According to the Centers for Disease Control and Prevention, an estimated 2.7 to 3.9 million people in the United States have chronic HCV. Some patients who suffer from chronic HCV infection over many years may have jaundice (yellowish eyes or skin) and develop complications, such as bleeding, fluid accumulation in the abdomen, infections, liver cancer and death.There are at least six distinct HCV genotypes, or strains, which are genetically distinct groups of the virus. Knowing the strain of the virus can help inform treatment recommendations. Approximately 75 percent of Americans with HCV have genotype 1; 20-25 percent have genotypes 2 or 3; and a small number of patients are infected with genotypes 4, 5 or 6.The safety and efficacy of Vosevi was evaluated in two Phase 3 clinical trials that enrolled approximately 750 adults without cirrhosis or with mild cirrhosis.The first trial compared 12 weeks of Vosevi treatment with placebo in adults with genotype 1 who had previously failed treatment with an NS5A inhibitor drug. Patients with genotypes 2, 3, 4, 5 or 6 all received Vosevi.The second trial compared 12 weeks of Vosevi with the previously approved drugs sofosbuvir and velpatasvir in adults with genotypes 1, 2 or 3 who had previously failed treatment with sofosbuvir but not an NS5A inhibitor drug.Results of both trials demonstrated that 96-97 percent of patients who received Vosevi had no virus detected in the blood 12 weeks after finishing treatment, suggesting that patients’ infection had been cured.Treatment recommendations for Vosevi are different depending on viral genotype and prior treatment history.The most common adverse reactions in patients taking Vosevi were headache, fatigue, diarrhea and nausea.Vosevi is contraindicated in patients taking the drug rifampin.Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected adult patients who were undergoing or had completed treatment with HCV direct-acting antivirals, and who were not receiving HBV antiviral therapy. HBV reactivation in patients treated with direct-acting antiviral medicines can result in serious liver problems or death in some patients. Health care professionals should screen all patients for evidence of current or prior HBV infection before starting treatment with Vosevi.The FDA granted this application Priority Review and Breakthrough Therapy designations. The FDA granted approval of Vosevi to Gilead Sciences Inc.
Vertex Announces Positive Phase 1 & Phase 2 Data from Three Different Triple Combination Regimens in People with Cystic Fibrosis Who Have One F508del Mutation and One Minimal Function Mutation (F508del/Min)
Phase 2 data showed mean absolute improvements in ppFEV1 of 9.7 and 12.0 percentage points for VX-152 and VX-440, respectively, in triple combination with tezacaftor and ivacaftor in F508del/Min patients; Initial data from Phase 1 study showed mean absolute improvement in ppFEV1 of 9.6 percentage points with VX-659 triple combination in F508del/Min patients- -First data to demonstrate the potential to treat the underlying cause of CF in people with F508del/Min mutations, a severe and difficult-to-treat type of the disease- -Initial Phase 2 data also showed mean absolute improvements in ppFEV1 of 7.3 and 9.5 percentage points when VX-152 or VX-440 was added in people with two copies of the F508del mutation (F508del/F508del), who were already receiving tezacaftor and ivacaftor- -All 3 triple combination regimens were generally well tolerated across the studies- BOSTON --(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced positive data from Phase 1 and Phase 2 studies of three different triple combination regimens in people with cystic fibrosis (CF) who have one F508del mutation and one minimal function mutation (F508del/Min). These are the first data to demonstrate the potential to treat the underlying cause of CF in these patients, who have a severe and difficult-to-treat type of the disease. Data from the Phase 2 studies in these patients showed mean absolute improvements in percent predicted forced expiratory volume in one second (ppFEV1) of 9.7 and 12.0 percentage points from baseline for the triple combination regimens with VX-152 (200mg q12h) or VX-440 (600mg q12h), respectively. Initial data from a Phase 1 study showed a mean absolute improvement in ppFEV1 of 9.6 percentage points from baseline for the triple combination regimen of VX-659, tezacaftor and ivacaftor in people with one F508del mutation and one minimal function mutation. The company also announced today initial data showing improvements in mean absolute ppFEV1 of 7.3 and 9.5 percentage points when VX-152 or VX-440 was added in people with two copies of the F508del mutation, who were already receiving tezacaftor and ivacaftor. Vertex will host a conference call for investors today, July 18, 2017 at 5:00 p.m. EDT , to discuss these results. The triple combination regimens were generally well tolerated across all three studies, and the majority of adverse events were mild to moderate in severity. Across the studies, the discontinuation rate due to adverse events was low. "These safety and efficacy data are clear and compelling, indicating significant potential benefit for people with CF from each of these three different triple combination regimens," said Jeffrey Chodakewitz , M.D., Executive Vice President and Chief Medical Officer at Vertex. "We will be collecting and evaluating additional data from these and other studies and will make a decision on which regimen(s) to take forward into pivotal program(s), which we expect to begin in the first half of 2018." Vertex has established a Steering Committee of global CF experts and clinical trial investigators to support the design, conduct and execution of the triple combination pivotal study program. This committee is co-chaired by Steven M. Rowe , M.D., M.S.P.H., Professor of Medicine, Pediatrics, and Cell, Developmental and Integrative Biology, Director of the Gregory Fleming James Cystic Fibrosis Research Center , Nancy and Eugene Gwaltney Endowed Chair for Medical Research , University of Alabama at Birmingham , and Jennifer Taylor-Cousar , M.D., Associate Professor, Departments of Medicine and Pediatrics, Pulmonary Divisions, Medical Director of Clinical Research Services and Co-Director and Director of the CF Therapeutics Development Network, Adult CF Program, National Jewish Health , Colorado . "Patients with minimal function mutations have been waiting for a medicine to treat the underlying cause of their disease, which makes these data showing pronounced improvements in lung function particularly important," said Dr. Rowe . "It's also encouraging to see that the addition of a next-generation corrector may lead to substantial additional benefits for patients with two copies of the F508del mutation, who were already receiving tezacaftor and ivacaftor." Next Steps Vertex has advanced four next-generation correctors in parallel with the goal of developing the best triple combination regimen or regimens for people living with CF. Vertex has accelerated the development programs for VX-445 and VX-659. A VX-445 Phase 2 study is underway and a VX-659 Phase 2 study will begin in early August. VX-445 and VX-659 will be evaluated in triple combination with tezacaftor and ivacaftor in people with one F508del mutation and one minimal function mutation and will be evaluated in people with two copies of the F508del mutation who are already receiving tezacaftor and ivacaftor. Data from both of these Phase 2 studies are expected in early 2018. Pending additional data from these Phase 2 studies and the ongoing studies of VX-152 and VX-440 and discussions with regulatory agencies and the Steering Committee, Vertex plans to initiate pivotal development of one or more triple combination regimens in the first half of 2018. About the VX-440 Phase 2 Study This randomized, double-blind Phase 2 study is evaluating VX-440 (200mg and 600mg q12h) in combination with tezacaftor and ivacaftor in two different groups of people with CF ages 18 and older - those who have one F508del mutation and one minimal function mutation, and in those who have two copies of the F508del mutation. Minimal function mutations are those that result in little-to-no functioning CFTR protein and are not responsive to ivacaftor, tezacaftor or the combination of ivacaftor and tezacaftor. The primary objectives for the study are safety, tolerability and efficacy as assessed by mean absolute change in ppFEV1 from baseline. Secondary endpoints include change in sweat chloride and Cystic Fibrosis Questionnaire-Revised (CFQ-R). Overall Safety Data: In the study, the triple combination regimen was generally well tolerated. The majority of adverse events were mild or moderate. The most common adverse events ( > 10%), regardless of treatment group, were infective pulmonary exacerbation, cough, sputum increased and diarrhea. There was one discontinuation due to an adverse event in the triple combination treatment groups (elevated liver enzymes > 5x upper limit of normal in the VX-440 600mg group) and one in the control groups (respiration abnormal and sputum increased). One additional patient treated with the triple combination had elevated liver enzymes ( > 8x upper limit of normal in the VX-440 600mg group), which were observed on the final day of dosing. In both patients, the elevated liver enzymes returned to normal after treatment discontinuation or completion. 4-Week Efficacy Data in F508del/Min Patients: Part 1 of the study evaluated the triple combination for four weeks in 47 patients who have one F508del mutation and one minimal function mutation (11 in placebo, 18 in VX-440 200mg and 18 in VX-440 600mg). A summary of the within-group lung function and sweat chloride data is provided below:
Array to Advance Preclinical Program for Autoimmune Disorders Amgen Responsible for Clinical Development and Worldwide Commercialization THOUSAND OAKS, Calif. and BOULDER, Colo., July 18, 2017 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and Array BioPharma (NASDAQ:ARRY) today announced a collaboration agreement for the discovery and development of novel drugs for autoimmune disorders. The undisclosed target and lead inhibitors were discovered through Array's proprietary platform that leverages Array's expertise in chemistry and early lead development."We are pleased to enter this collaboration with Array that builds on our continued focus in inflammation, one of Amgen's key strategic areas of interest," said Flavius Martin, M.D., vice president of Research, Inflammation and Oncology at Amgen. "We look forward to partnering with Array BioPharma to advance molecules into the clinic that may offer a new treatment option for patients.""We look forward to collaborating with Amgen, a leader in treatments for inflammatory disease, on this exciting target which was discovered using Array's proprietary Kinase-Directed Phenotypic Screening Platform," said Nicholas A. Saccomano, Ph.D., chief scientific officer at Array BioPharma. "The identification of this novel target, along with our team's deep experience in kinase inhibitor chemistry, gives us confidence that our efforts will result in a drug which will address a significant unmet medical need for patients with inflammatory disease."Under the terms of the agreement, Amgen and Array will collaborate on preclinical development with Array leading the medicinal chemistry work. Amgen is responsible for clinical development and commercialization. In exchange for exclusive rights to Array's preclinical program, Amgen will make upfront and milestone payments, as well as pay royalties on sales of resulting therapies.About Amgen Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.About Array BioPharma Array BioPharma Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule drugs to treat patients afflicted with cancer. Eight registration studies are currently advancing related to six Array-owned or partnered drugs: binimetinib (MEK162), encorafenib (LGX818), selumetinib (partnered with AstraZeneca), danoprevir (partnered with Roche), ipatasertib (partnered with Genentech), larotrectinib (partnered with Loxo Oncology) and tucatinib (partnered with Cascadian Therapeutics).
Centrexion Therapeutics Provides Updates and Advancements for Pipeline of Chronic Pain Treatments
BOSTON--(EON: Enhanced Online News)--Centrexion Therapeutics, a company focused on advancing the treatment of chronic pain with one of the largest exclusively pain-focused pipelines of non-opioid therapies in active development, today provided an update on the company’s therapeutics in development to treat chronic pain. The company next plans to initiate a Phase 2 study evaluating its somatostatin receptor type 4 (SSTR4) agonist – CNTX-0290, a brand-new target for therapeutic development.“Given the growing problem of chronic pain that we face, it is critically important that we have new non-opioid treatment options with potential to treat different kinds of pain, including difficult to treat pain” “Given the growing problem of chronic pain that we face, it is critically important that we have new non-opioid treatment options with potential to treat different kinds of pain, including difficult to treat pain,” said Randall M. Stevens, M.D., chief medical officer of Centrexion Therapeutics. “Because CNTX-0290 has a novel mechanism of action that targets a ‘master control’ switch for pain, it has the potential to significantly benefit a broad population of people suffering from chronic pain, including mixed pain conditions such as back pain. It is critical that we continue to advance new pain treatments like CNTX-0290 that have the potential to relieve pain while avoiding the significant challenges and side effects of currently available therapies.”CNTX-0290: Phase 1 Completed, Patent AwardedIn single- and multiple-ascending-dose Phase 1 studies of CNTX-0290, the potent and selective SSTR4 agonist, was well tolerated by subjects in all cohorts, including the elderly, and was well absorbed after oral dosing with good pharmacokinetics and no food effect on absorption. Data from the Phase 1 trials will be presented at an upcoming medical meeting.The indications for the Phase 2 trial will be selected based on Centrexion Therapeutics’ big data approach, leveraging genetics, proteomics, in vitro, in vivo and clinical data to identify the types of chronic pain that are most likely to be impacted by treatment with CNTX-0290.Additionally, Centrexion Therapeutics recently received a notice of allowance from the U.S. Patent and Trademark Office for a patent covering compounds targeting the SSTR4 receptor.About CNTX-0290CNTX-0290 is a new drug target with significant potential for development of a totally new class of pain therapeutics. CNTX-0290 works by activating the SSTR4 receptor, which functions as a “master control” switch to turn down the activity of several other pain receptors, such as specific calcium channels, potassium channels and TRPV1 and TRPA1 channels, thereby reducing the transmission of pain signals. To date, CNTX-0290 has shown activity in every chronic pain model it has been tested in and shows promise for treating a wide variety of chronic pain conditions.Additional ProgressEarlier this year Centrexion Therapeutics received approval of two Investigational New Drug (IND) applications from the U.S. Food and Drug Administration (FDA) to initiate Phase 1 trials of CNTX-6970 and CNTX-6016 in the U.S.CNTX-6970 is a novel, potent and selective CCR2 antagonist with a unique analgesic profile. Recent studies have shown a close link between chronic pain and the immune system. CNTX-6970 capitalizes on this connection by taking a novel “neuro-immune” approach. The compound has a dual effect: stopping immune cells from releasing the potent cytokine CCL2 and stopping CCL2 from stimulating pain fibers to send pain signals. CNTX-6970 is predicted to be well suited to treat chronic painful inflammatory conditions such as osteoarthritis, and current studies show the treatment is safe and well tolerated with demonstrated pharmacologic activity. CNTX-6970 has successfully completed Phase 1 single-ascending-dose studies which not only showed it was well tolerated with an acceptable pharmacokinetic profile but also demonstrated target engagement.CNTX-6016 is the first of the new generation, potent and “super selective” cannabinoid CB2 agonists. CB2 agonists are 20,000 times more selective for the CB2 receptor than the CB1, and thereby result in pain relief without psychotropic and other side effects seen with less selective agonists. CNTX-6016 could serve as a promising solution for chronic pain conditions such as diabetic neuropathic pain.Centrexion Therapeutics expects to announce initial readouts for CNTX-6016 and CNTX-6970 in the first half of 2018.“Centrexion Therapeutics continues to make outstanding progress in its mission to address the substantial and growing chronic pain epidemic by developing the largest, exclusively pain-focused pipeline of non-opioid therapies,” said Jeffrey B. Kindler, chief executive officer of Centrexion Therapeutics. “Following our June announcement of six-month data for CNTX-4975, which showed significant and durable response for the treatment of chronic pain associated with knee osteoarthritis with just a single treatment, we continue to see progress with our additional pipeline candidates, as well. We believe these combined efforts will result in new therapies that will help bridge the safety and efficacy gaps in current chronic pain treatment and ease the burden chronic pain places on patients and our healthcare system.”About the Burden of Chronic PainChronic pain affects 100 million people in the U.S. and 270 million people worldwide, and currently available treatments often lack adequate efficacy and are associated with numerous side effects. The total annual incremental cost of health care due to pain ranges from 0 billion to 5 billion in the U.S., which combines the medical costs of pain care and the economic costs related to disability days, lost wages and productivity. Despite the availability of a variety of pain treatment options ranging from opioids and NSAIDs, to hyaluronic acid and surgery, millions of people continue to live with chronic, debilitating pain.About Centrexion TherapeuticsCentrexion Therapeutics, Corp. is focused on advancing the treatment of chronic moderate to severe pain with one of the largest exclusively pain-focused pipelines of non-opioid therapies in active development. Centrexion Therapeutics recognizes the needs of over a quarter of a billion patients living with chronic pain worldwide, and aims to develop new, safer and more effective therapies that overcome the limitations and challenges associated with current pain treatments. Founded by world-renowned leaders in drug development and well-funded by key investors, Centrexion Therapeutics is building a pain treatment powerhouse to address the substantial and growing global chronic pain epidemic. Centrexion Therapeutics has recently relocated from Baltimore, Md. to Boston, Mass.For more information about Centrexion, visit http://www.centrexion.com.
U.S. Food and Drug Administration Approves Puma’s NERLYNX™ (neratinib) for Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer
LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (Nasdaq: PBYI) today announced that the U.S. Food and Drug Administration (FDA) has approved NERLYNX™ (neratinib), formerly known as PB272, a once-daily oral tyrosine kinase inhibitor for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy. Puma expects neratinib to become commercially available in September 2017 and to be marketed as NERLYNX.“New and effective innovative therapeutic options provide huge hope to patients and their families, giving them a better chance of overcoming breast cancer with a chance for a full life.” Tweet this FDA approval was based on the Phase III ExteNET trial, a multicenter, randomized, double-blind, placebo-controlled trial of neratinib following adjuvant trastuzumab treatment. Women (n=2,840) with early-stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year.The results of the ExteNET trial demonstrated that after two years of follow-up, invasive disease-free survival (iDFS) was 94.2% in patients treated with neratinib compared with 91.9% in those receiving placebo (HR 0.66; 95% CI: 0.49, 0.90, p=0.008).The most common adverse reactions (>5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. The most common adverse reaction leading to discontinuation was diarrhea, which was observed in 16.8% of neratinib-treated patients. Hepatotoxicity or increases in liver transaminases led to drug discontinuation in 1.7% of neratinib-treated patients."The fear of recurrence is ever present in the minds of most women with breast cancer, from the moment they are diagnosed to long after they finish adjuvant treatment," said Marisa C. Weiss, M.D., Chief Medical Officer and Founder of Breastcancer.org. “New and effective innovative therapeutic options provide huge hope to patients and their families, giving them a better chance of overcoming breast cancer with a chance for a full life.”“Despite advances in the treatment of early stage HER2-positive breast cancer, there remains a need for further therapeutic improvements in order to attempt to further reduce the risk of disease recurrence,” said Puma Biotechnology CEO and President Alan H. Auerbach. “We are pleased to be able to bring this new medicine to patients with breast cancer. We would like to express our appreciation to the patients, caregivers and physicians who contributed to the neratinib clinical development program and, more specifically, the ExteNET trial.”The full prescribing information for NERLYNX will be made available at WWW.NERLYNX.COM. The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first NERLYNX dose and continued during the first 2 cycles (56 days) of treatment and as needed thereafter. A Marketing Authorisation Application for neratinib is under review by the European Medicines Agency (EMA).About HER2-Positive Breast CancerApproximately 20 to 25 percent of breast cancer tumors over-express the HER2 protein. HER2-positive breast cancer is often more aggressive than other types of breast cancer, increasing the risk of disease progression and death. Although research has shown that trastuzumab can reduce the risk of early stage HER2-positive breast cancer returning after surgery, up to 25% of patients treated with trastuzumab experience recurrence.