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Phase III data showed that Venclexta/Venclyxto plus MabThera/Rituxan helped people with previously treated chronic lymphocytic leukaemia live longer without their disease worsening compared to bendamustine plus MabThera/Rituxan

On September 18, 2017 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the phase III MURANO study, which evaluated Venclexta/Venclyxto (venetoclax) in combination with MabThera/Rituxan (rituximab) in people with relapsed or refractory chronic lymphocytic leukaemia (CLL), met its primary endpoint and showed a statistically significant improvement in the time people lived without their disease progressing (progression-free survival [PFS] as assessed by investigator) when treated with Venclexta/Venclyxto plus MabThera/Rituxan compared to bendamustine plus Mabthera/Rituxan (Press release, Hoffmann-La Roche, SEP 18, 2017, View Source [SID1234520551]). No new safety signals or increase in known toxicities of Venclexta/Venclyxto were observed with the treatment combination of Venclexta/Venclyxto plus Mabthera/Rituxan. Venclexta/Venclyxto (venetoclax) is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialised by AbbVie outside of the United States.

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"Chronic lymphocytic leukaemia is considered incurable and becomes harder to treat with each relapse," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "This is the first study to show that Venclexta/Venclyxto plus Mabthera/Rituxan can help people with this type of leukaemia live significantly longer without their disease worsening compared to a standard-of-care regimen. We will work with health authorities to bring this potential chemotherapy-free treatment option to the people who need it as quickly as possible."

In January 2016, Roche announced that the US Food and Drug Administration (FDA) granted breakthrough therapy designation for Venclexta/Venclyxto in combination with Mabthera/Rituxan for the treatment of relapsed or refractory CLL based on promising results from the phase Ib M13-365 study. Breakthrough therapy designation is intended to expedite the development and review of medicines with early evidence of potential clinical benefit in serious or life-threatening diseases and to help ensure that patients receive access to medicines as soon as possible.

Venclexta/Venclyxto was granted accelerated approval by the FDA in April 2016 for the treatment of people with CLL with 17p deletion, as detected by an FDA approved test, who have received at least one prior therapy. The MURANO study is part of the company’s commitment in the United States to convert the current accelerated approval of Venclexta/Venclyxto to a full approval. Data from the MURANO study will be presented at an upcoming medical meeting and submitted to global health authorities.

About the MURANO Study
MURANO (NCT02005471) is a phase III open-label, international, multicentre, randomized study evaluating the efficacy and safety of Venclexta/Venclyxto in combination with Mabthera/Rituxan compared with bendamustine in combination with Mabthera/Rituxan. All treatments were of fixed duration. The study included 389 patients with relapsed or refractory CLL who had been previously treated with at least one but not more than three lines of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta/Venclyxto plus Mabthera/Rituxan (Arm A) or bendamustine plus Mabthera/Rituxan (Arm B). The primary endpoint of the study is investigator-assessed PFS. Secondary endpoints include PFS assessed by independent review committee (IRC), best overall response, complete response, duration of response, overall survival, event-free survival, time to next CLL treatment and minimal residual disease (MRD) status.

About Venclexta/Venclyxto
Venclexta/Venclyxto is a small molecule designed to selectively bind and inhibit the BCL-2 protein, which plays an important role in a process called apoptosis (programmed cell death). Overexpression of the BCL-2 protein in CLL has been associated with resistance to certain therapies. It is believed that blocking BCL-2 may restore the signaling system that tells cells, including cancer cells, to self-destruct. Venclexta/Venclyxto is being developed by AbbVie and Roche. It is jointly commercialised by AbbVie and Genentech, a member of the Roche Group, in the United States and commercialised by AbbVie outside of the United States.

Together, the companies are committed to further research with Venclexta/Venclyxto, which is currently being evaluated in phase III clinical trials for the treatment of CLL, along with studies in several other types of cancers. In the United States, Venclexta has been granted four breakthrough therapy designations by the FDA: in combination with Rituxan for people with relapsed or refractory CLL; as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated acute myeloid leukemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine (LDAC) for people with untreated AML ineligible for intensive chemotherapy.

About Chronic Lymphocytic Leukaemia (CLL)
Chronic lymphocytic leukaemia (CLL) is the most common type of leukaemia in the Western world.1 CLL mainly affects men and the median age at diagnosis is about 70 years2. Worldwide, the incidence of all leukaemias is estimated to be over 350,0001 and CLL is estimated to affect around one-third of all people newly diagnosed with leukaemia.3

TOLREMO Raises CHF 2.4 Million in Seed Financing

On September 18, 2018 TOLREMO therapeutics AG ("TOLREMO"), a privately held research-stage biotechnology company, reported the completion of a fundraiser with private investors of 2.4 million Swiss Francs (Press release, TOLREMO, SEP 18, 2017, View Source [SID1234525826]). The proceeds will be used to advance the company’s discovery and development of breakthrough medicines to target drug resistance in cancer therapy.

Dr. Stefanie Flückiger-Mangual, Chief Executive Officer and co-founder of TOLREMO, commented: "Cancer patients often respond favorably to modern therapies, but in many cases long-term survival is limited by the development of drug resistance. During several years of research at ETH Zurich, we discovered that, surprisingly, the development of drug resistance already starts early on following initiation of cancer therapy. We have developed a deep understanding of the molecular mechanisms involved in this and our goal is to intervene with these mechanisms in order to eradicate the seed of drug resistance and extend patient survival."

TOLREMO’s science-based drug discovery and development pipeline is fueled by a unique drug screening platform for which a patent has been filed. In addition to discovering and developing novel anti-drug resistance molecules, the platform is also used to identify novel ways of combining approved drugs to prevent drug resistance in cancer therapy.

Dr. Isaac Kobrin, Chairman of the Board and a co-founder of TOLREMO, commented: "We believe that TOLREMO is poised to reach several key milestones in the development of novel cancer therapies within the next 12 to 18 months. The currently raised funds of 2.4 million Swiss Francs are expected to cover that period and prepare the grounds for the future growth of the company."

Karus Therapeutics Announces First Cancer Patients Dosed with KA2507, a Small Molecule HDAC6-Selective Inhibitor, in a Phase I Clinical Trial

On September 18,2017 Karus Therapeutics Ltd (‘Karus’), a leader in the design and development of innovative medicines with breakthrough potential in the treatment of cancer, reported that the first patients have been dosed with its histone deacetylase 6 (HDAC6) inhibitor, KA2507, in a Phase I clinical study (Press release, Karus Therapeutics, SEP 18, 2017, View Source [SID1234520560]). This is the Company’s second orally-active small molecule cancer therapeutic agent to enter clinical trials during the past 12 months.

This Phase I study has been designed to assess the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of KA2507 in patients with PD-L1-expressing solid tumors. The trial is being conducted at the University of Texas MD Anderson Cancer Center in Houston, Texas, USA, and is part of a collaboration between the two organizations.

KA2507 is a highly-selective and potent inhibitor of the tubulin deacetylase, HDAC6. Selective inhibition of this enzyme confers a cancer immunotherapeutic response by regulating immune checkpoint markers within the tumor microenvironment. HDAC6 has also emerged as a potentially important therapeutic target due to its overexpression in solid tumors and its role in specific mutant-harboring cancers. Karus considers KA2507 to hold broad therapeutic potential for the treatment of solid tumors, as both a single agent and in combination with other drugs.

Stephen Shuttleworth – COO, CSO and founding scientist of Karus’s R&D programs – commented: "KA2507 is Karus’s second small molecule cancer therapeutic agent designed in our laboratories to enter Phase I trials within the last year, and the commencement of this clinical study represents another significant milestone for the Company. HDAC6 is an exciting new target in cancer, and KA2507 is the product of many years’ research and development. The drug has the potential to be a best-in-class agent, and represents another major step in our mission towards the development of new life-changing therapies for cancer patients."

Apostolia Tsimberidou MD, PhD, Professor in the Department of Investigational Cancer Therapeutics at the MDACC is the Principal Investigator for the clinical study.

Autolus Announces Initiation of the AMELIA and ALEXANDER Studies for AUTO3: Phase I/II Studies in paediatric ALL and DLBCL

On September 18, 2017 UCL Business spinout company, Autolus Limited, a clinical-stage biopharmaceutical company focused on the development and commercialisation of next-generation engineered T-cell therapies, reported initiation of both the AMELIA and ALEXANDER phase I/II studies of its novel, dual-targeting, AUTO3 Chimeric Antigen Receptor (CAR) T-cell therapy (Press release, UCLB, SEP 18, 2017, View Source [SID1234520559]).

AUTO3 is an autologous T-cell product, genetically modified to express two separate CARs which recognise CD19 and CD22; two antigens expressed by cancer cells in B-cell leukaemia and lymphoma. AUTO3 is designed to minimise the risk of relapse due to antigen loss, a key mechanism of resistance shown in single antigen targeting CAR-T therapies.

The AMELIA and ALEXANDER Studies are dose-escalation phase I/II studies in paediatric Acute Lymphocytic Leukaemia (ALL) and adult Diffuse Large B-Cell Lymphoma (DLBCL) in which cohorts of patients receive ascending doses of AUTO3 to determine the maximum tolerated dose and establish a recommended dose. The second part of the study is an expansion phase where patients receive AUTO3 to further evaluate the safety, tolerability and clinical activity at this recommended dose. In addition to the effects of AUTO3 alone, combination with short-duration use of a checkpoint inhibitor is also being evaluated in the ALEXANDER study.

Dr Martin Pule, Autolus’ Founder and Chief Scientific Officer said:

"Our approach at Autolus is to understand how tumours defend against T-cells and then design and programme CAR-T cell products which specifically address those defence and escape mechanisms. The AUTO3 programme seeks to overcome two limitations of current therapies by introducing dual targeting CARs and addressing checkpoint mediated inhibition."

Professor Persis Amrolia, Professor of Transplantation Immunology, Great Ormond Street Hospital, London commented:

"The advent of CD19 CAR-T cell based therapy is an exciting and revolutionary advancement in the treatment of children with relapsed ALL. However, in approximately a third of the patients the disease reoccurs by losing CD19 antigen. AUTO3, a dual targeting CAR, addresses this challenge by independently targeting CD19 and CD22 antigen, which has the promise of reducing antigen escape."

Dr Anas Younes, Chief, Lymphoma Service at Memorial Sloan Kettering Cancer Center, New York commented:

"CD19-directed CAR-T cell therapies already offer the possibility of an important new treatment option for patients with relapsed and refractory DLBCL. AUTO3 is a novel approach which simultaneously targets a second clinically relevant antigen, CD22. The field is looking forward to seeing how patients respond to AUTO3 in clinical trials and whether dual antigen targeting CAR-T cell therapy offers the possibility of deeper initial and more sustained responses."

U.S. FDA Approves New Indication for Ipsen’s Somatuline® Depot (lanreotide) Injection for the Treatment of Carcinoid Syndrome

On September 18, 2017 Ipsen (Euronext: IPN; ADR: IPSEY) (Ipsen), reported that the U.S. Food and Drug Administration (FDA) has approved a supplemental indication for Somatuline Depot (lanreotide) Injection 120 mg for the treatment of carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analogue rescue therapy (Press release, Ipsen, SEP 18, 2017, View Source [SID1234520558]).

Somatuline Depot is also approved for the improvement of progression-free survival (PFS) in patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).[1]

Alexandre Lebeaut, MD, Executive Vice-President, R&D, Chief Scientific Officer, Ipsen, said: "The new indication for Somatuline Depot offers patients in the U.S. a valuable treatment option for debilitating carcinoid syndrome associated with neuroendocrine tumors. It also reaffirms Ipsen’s global commitment to helping to improve lives of patients with cancer."

"This new indication for Somatuline Depot gives doctors the only somatostatin analog approved by the FDA in adults for both improving progression-free survival in patients with unresectable, well- or moderately- differentiated, locally advanced or metastatic GEP-NETs and for the treatment of carcinoid syndrome," said Cynthia Schwalm, Executive Vice-President, and President, North American Commercial Operations, Ipsen. "The additional approval also confirms Ipsen’s commitment to developing research-driven treatments intended to help provide patients battling cancer with new therapy options."

The additional Somatuline Depot approval for carcinoid syndrome was based on "Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment (ELECT): A Randomized, Double-Blind, Placebo-Controlled Trial," published in Endocrine Practice.1,2

IMPORTANT SAFETY INFORMATION

Contraindications

Somatuline Depot is contraindicated in patients with hypersensitivity to lanreotide. Allergic reactions (including angioedema and anaphylaxis) have been reported following administration of lanreotide.
Warnings and Precautions

Cholelithiasis and Gallbladder Sludge
Somatuline Depot may reduce gallbladder motility and lead to gallstone formation.
Periodic monitoring may be needed.
Hypoglycemia or Hyperglycemia
Pharmacological studies show that Somatuline Depot, like somatostatin and other somatostatin analogs, inhibits the secretion of insulin and glucagon. Patients treated with Somatuline Depot may experience hypoglycemia or hyperglycemia.
Blood glucose levels should be monitored when Somatuline Depot treatment is initiated, or when the dose is altered, and antidiabetic treatment should be adjusted accordingly.
Cardiovascular Abnormalities
Somatuline Depot may decrease heart rate.
In patients in the GEP-NET pivotal trial, 23% of Somatuline Depot-treated patients had a heart rate of less than 60 bpm compared to 16% of placebo-treated patients. The incidence of bradycardia was similar in the treatment groups. Initiate appropriate medical management in patients with symptomatic bradycardia.
In patients without underlying cardiac disease, Somatuline Depot may lead to a decrease in heart rate without necessarily reaching the threshold of bradycardia. In patients suffering from cardiac disorders prior to treatment, sinus bradycardia may occur. Care should be taken when initiating treatment in patients with bradycardia.
Most Common Adverse Reactions

GEP-NETs: Adverse reactions occurring in greater than 10% of patients who received Somatuline Depot in the GEP-NET trial were abdominal pain (34%), musculoskeletal pain (19%), vomiting (19%), headache (16%), injection site reaction (15%), hyperglycemia (14%), hypertension (14%), and cholelithiasis (14%).
Carcinoid Syndrome: Adverse reactions occurring in the carcinoid syndrome trial were generally similar to those in the GEP-NET trial. Adverse reactions occurring in greater than 5% of patients who received Somatuline Depot in the carcinoid syndrome trial and occurring at least 5% greater than placebo were headache (12%), dizziness (7%) and muscle spasm (5%).
Drug Interactions: Somatuline Depot may decrease the absorption of cyclosporine (dosage adjustment may be needed); increase the absorption of bromocriptine; and require dosage adjustment for bradycardia-inducing drugs (e.g., beta-blockers).

Special Populations

Lactation: Advise women not to breastfeed during treatment and for 6 months after the last dose.
To report SUSPECTED ADVERSE REACTIONS, contact Ipsen Biopharmaceuticals, Inc. at +1-855-463-5127 or FDA at +1-800-FDA-1088 or www.fda.gov/medwatch.

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