On October 13, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Union’s (EU) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the approval of Alecensa (alectinib) as a monotherapy for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive, advanced non-small cell lung cancer (NSCLC). It has also simultaneously recommended the conversion of the current conditional marketing authorisation for Alecensa in crizotinib failure (second-line) to a full marketing authorisation.

The CHMP recommendation in first-line is based on results from the global phase III ALEX study, which showed Alecensa significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by 53% (HR=0.47, 95% CI: 0.34-0.65, p<0.001) compared with crizotinib. The study also showed that Alecensa reduced the risk of tumours spreading to, or growing in, the brain or central nervous system (CNS) by 84% (HR=0.16, 95% CI: 0.10-0.28, p<0.001), compared with crizotinib. The safety and tolerability profile of Alecensa compared favourably to that of crizotinib despite the longer duration of treatment with Alecensa (17.9 vs. 10.7 months), and was consistent with that observed in previous studies.1 "This is more great news for people with this type of lung cancer, bringing them closer to benefiting from Alecensa’s superior efficacy earlier in their treatment journey," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The results from ALEX clearly showed the significant benefits of Alecensa over crizotinib and we are pleased this has been recognised by the CHMP." The next step would be for the European Commission to make its final decision. A positive decision would mean approval for Alecensa across both the first-line and crizotinib failure settings in Europe. Alecensa was recently granted Priority Review by the U.S. Food and Drug Administration (FDA) in the first-line setting in the United States, and has been approved in the crizotinib failure setting since 2015.2 About the ALEX study ALEX (NCT02075840/B028984) is a randomised, multicentre, open-label phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in treatment-naïve people with ALK-positive NSCLC whose tumours were characterised as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, a companion immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. People were randomised (1:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALEX study is PFS as assessed by the investigator, and secondary endpoints include: Independent Review Committee (IRC)-assessed PFS, time to CNS progression, objective response rate (as defined by RECIST criteria), duration of response, overall survival, health-related quality of life and safety. The multicentre study was conducted in 303 people across 161 sites in 31 countries.3 Results include: Alecensa reduced the risk of disease worsening or death (PFS) by 53% compared to crizotinib (HR=0.47, 95% CI: 0.34-0.65, p<0.001). Investigator-reported median PFS (the primary endpoint) was not yet reached in the Alecensa arm (95% CI: 17.7 -not reached) versus 11.1 months (95% CI: 9.1-13.1 months) in the crizotinib arm. IRC-reported median PFS (a secondary endpoint) was 25.7 months (95% CI: 19.9-not estimable) in the Alecensa arm versus 10.4 months (95% CI: 7.7-14.6 months) in the crizotinib arm (HR=0.50, 95% CI: 0.36-0.70; p<0.001). Alecensa reduced the risk of progression in the CNS by 84% (HR=0.16, 95% CI: 0.10-0.28; p<0.001). The 12-month cumulative rate of CNS progression for people with or without existing CNS metastases at baseline was 9.4% (95% CI: 5.4-14.7%) for people treated with Alecensa and 41.4% (95% CI: 33.2-49.4%) for people treated with crizotinib. Overall survival (OS) data are still immature with only about a quarter of events being reported. Grade 3-5 adverse events (AEs) were less frequent in the Alecensa arm (41%) compared with the crizotinib arm (50%). In the Alecensa arm, the most common Grade 3-5 AEs (≥5%) were increased liver enzymes (alanine transferase and aspartate transferase; 5%) and decreased red blood cells (anaemia; 5%). AEs leading to discontinuation (11% vs. 13%), dose reduction (16% vs. 21%) and dose interruption (19% vs. 25%) were all lower in the Alecensa arm compared with the crizotinib arm. About Alecensa Alecensa (RG7853/AF-802/RO5424802/CH5424802) is a highly selective, CNS active, oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. 4 It is almost always found in people with a specific type of NSCLC called adenocarcinoma.4 Alecensa is currently approved in the United States, Europe, Kuwait, Israel, Hong Kong, Canada, South Korea, Switzerland, India, Australia, Singapore, Taiwan, Thailand, Liechtenstein, Argentina, United Arab Emirates, Saudi Arabia and Turkey for the treatment of people with advanced (metastatic) ALK-positive NSCLC whose disease has worsened after, or who could not tolerate treatment with, crizotinib and in Japan for people with ALK-positive NSCLC. About Roche in lung cancer Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have four approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

Roche’s Erivedge could be removed from the Cancer Drugs Fund within months after the National Institute for Health and Care Excellence ruled that the drug was not a cost-effective treatment for skin cancer (Press release, PharmaTimes, OCT 13, 2017, View Source [SID1234520892]).

On October 13, 2017 Shire plc (LSE: SHP, NASDAQ: SHPG), the global leader in rare diseases, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the marketing authorization for lyophilized ONCASPAR (pegaspargase), as a component of antineoplastic combination therapy in acute lymphoblastic leukemia (ALL) in pediatric patients from birth to 18 years, and in adult patients. Lyophilized ONCASPAR is a freeze-dried formulation of ONCASPAR (Press release, Shire, OCT 13, 2017, View Source [SID1234520886]). The liquid form of ONCASPAR is currently approved for the same indication in ALL, and is part of the pediatric standard therapy in ALL in many European countries.1 The CHMP’s positive opinion will be submitted to the European Commission (EC), which is responsible for granting marketing authorizations for medicines in the EU.

Acute lymphoblastic leukemia (ALL) is a cancer of the white blood cells and is characterized by an overproduction and accumulation of lymphoblasts, immature white blood cells. ALL is the most common type (~75%) of cancer among children diagnosed with leukemia.2 ALL can be curable within certain pediatric patient populations, with a 5-year survival rate of more than 90% in children treated with regimens including ONCASPAR.3,4,5,

“Lyophilized ONCASPAR builds on more than a decade of data and research with liquid ONCASPAR, and with no change in dosing regimen, it offers a three-times longer shelf life,” said Howard B. Mayer, M.D., SVP and ad-interim Head, Global Research and Development, Shire. “Prolonging shelf life to 24 months for this critically-important therapy facilitates management of product inventory by enabling greater flexibility and longer-term planning. Once approved, with the extended shelf life of lyophilized ONCASPAR, we also hope to improve access to the medicine for ALL patients in countries currently not offering liquid ONCASPAR.”

Lyophilized ONCASPAR works the same way as the liquid formulation by rapidly depleting serum L-asparagine levels and interfering with protein synthesis, thereby depriving lymphoblasts of asparaginase and resulting in cell death. That is why asparaginase is a critical component of the treatment regimen for ALL patients as it is a proven approach to inducing leukemic cell death.4,6,7,8,9,10,11,

About Lyophilized ONCASPAR
Lyophilized ONCASPAR builds on more than a decade of data and research with liquid ONCASPAR, a pegylated asparaginase. The positive opinion is based on analytical and nonclinical studies, which demonstrate that the lyophilized formulation of ONCASPAR is comparable to the liquid formulation. Once reconstituted, lyophilized ONCASPAR demonstrates similar pharmacokinetic (PK)/pharmacodynamics (PD) to liquid ONCASPAR.1 The new lyophilized formulation offers no change in dosing regimen but a longer shelf life that is three times that of the liquid formation.1

About ONCASPAR
In Europe, ONCASPAR is indicated as a component of antineoplastic combination therapy in acute lymphoblastic leukemia (ALL) in pediatric patients from birth to 18 years, and adult patients.

ONCASPAR can be given by intramuscular injection or intravenous infusion. For smaller volumes of ONCASPAR, the preferred route of administration is intramuscular. When ONCASPAR is given by intramuscular injection the volume injected at one site should not exceed 2 ml in children and adolescents and 3 ml in adults. If higher volume is given, the dose should be divided and given at several injection sites. Intravenous infusion of ONCASPAR is usually given over a period of 1 to 2 hours in 100 ml sodium chloride 9 mg/ml (0.9%) solution for injection or 5% glucose solution. The diluted solution of ONCASPAR can be given together with an already-running infusion of either sodium chloride 9 mg/ml or 5% glucose. Do not infuse other medicinal products through the same intravenous line during administration of ONCASPAR.

Safety Information
ONCASPAR is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients, in patients with severe hepatic impairment, and in patients with a history of serious thrombosis, pancreatitis, or serious haemorrhagic events with prior L-asparaginase therapy.

Anaphylaxis or serious allergic reactions can occur; therefore, patients should be observed for 1 hour after administration having resuscitation equipment ready. Discontinue ONCASPAR in patients with serious allergic reactions. There have been reports of adverse reactions of pancreatitis. If pancreatitis is suspected ONCASPAR should be discontinued. ONCASPAR should also be discontinued in patients with serious thrombotic events.

Combination therapy with ONCASPAR can result in hepatic toxicity and central nervous system toxicity. Appropriate monitoring should be performed for liver impairment, blood and urine glucose levels as well as serum amylase for early signs of inflammation of the pancreas.

The very common adverse reactions reported in clinical trial data and the post-marketing experience of ONCASPAR in ALL patients include: hyperglycemia, pancreatitis, diarrhea, abdominal pain, nausea, vomiting, stomatitis, hypersensitivity, urticaria, anaphylactic reaction, weight decreased, decreased appetite, and rash.

Common adverse reactions include: febrile neutropenia, anemia, coagulopathy, hepatotoxicity, fatty liver, infections, sepsis, amylase increased, alanine aminotransferase increased, blood bilirubin increased, blood albumin decreased, neutrophil count decreased, platelet count decreased, activated partial thromboplastin time prolonged, prothrombin time prolonged, hypofibrinogenemia, hypertriglyceridemia, hyperlipidemia, hypercholesterolemia, pain in extremities, seizure, peripheral motor neuropathy, syncope, posterior reversible leukoencephalopathy syndrome, hypoxia, and thrombosis.

On October 13, 2017 OncoSec Medical Incorporated (“OncoSec”) (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported that the Company will host its fiscal fourth quarter and 2017 year-end financial results conference call on Wednesday, October 25th at 1:15 PM PT/4:15 PM ET (Press release, OncoSec Medical, OCT 13, 2017, View Source [SID1234520916]).

To access the audio broadcast, please dial (877) 731- 1960 and enter the conference ID number: 86520374. An archived version of the presentation will be available for 90 days on the “Investors” section of OncoSec’s website: View Source