On March 26, 2019 Zenyaku Kogyo Co., Ltd. (Japanese-only website) and Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that Zenyaku obtained regulatory approval from the Ministry of Health, Labour and Welfare (MHLW), for an anti-CD20 monoclonal antibody, RITUXAN injection 100 mg and 500 mg [generic name: rituximab (genetical recombination)] (hereafter, "RITUXAN"), which was co-developed by the two companies for an additional indication of CD20-positive chronic lymphocytic leukemia (CLL) (Press release, Chugai, MAR 26, 2019, View Source [SID1234534622]). RITUXIAN is co-marketed by the two companies in Japan.

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RITUXAN is an anti-CD20 monoclonal antibody that specifically binds to CD20, a protein expressed on B cells other than stem and plasma cells, which attacks B cells as targets with the immune system in the body. RITUXAN is used in combination with other antineoplastic drugs for the treatment of CD20-positive CLL, the additional indication approved this time.

CLL is a disease in which small mature B lymphocytes proliferate monoclonally and proliferate in peripheral blood, bone marrow, lymph nodes and spleen, many of which progress slowly. This rare disease is mostly prevalent in elderly people, and considered as difficult to cure with current treatments while many patients often experience recurrence and progression repeatedly. The number of patients in Japan is small, reportedly about 0.3 to 100,000 people per year. The age of onset is typically over 50 years, and rarely seen in people under 30 years of age. In patients with CLL, the ratio of males to females is higher at about 1.5 or 2 to 1*.

Zenyaku and Chugai will continue to work closely together to make RITUXAN contribute to the treatment of CD20-positive CLL.

* Center for Cancer Control and Information Services. Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma
View Source (Japanese only)

on March 26, 2019 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has obtained regulatory approval for the humanized anti-human IL-6 receptor monoclonal antibody, "Actemra Intravenous Infusion 80 mg, 200 mg, and 400 mg" [generic name: tocilizumab (genetical recombination)] from the Ministry of Health, Labour and Welfare (MHLW) for an additional indication of "cytokine release syndrome induced by tumor-specific T cell infusion therapy" and an additional dosing regimen for cytokine release syndrome (CRS) (Press release, Chugai, MAR 26, 2019, View Source [SID1234534619]). CRS is an adverse reaction associated with chimeric antigen receptor (CAR)-T cell therapy. It is caused by overactive immune response, leading to death if aggravated. CAR-T cell therapy is a type of tumor-specific T cell infusion therapies.

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"We are very pleased to gain additional approval which enables us to provide Actemra as the first approved treatment in Japan for the treatment of CRS induced by CAR-T cell therapy," said Dr. Yasushi Ito, Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit. "We will continue our efforts for safety information collection and prompt information provision to healthcare providers so that they can use the drug for their patients with confidence."

The approval is based on the results of two global phase II studies conducted by Novartis, to investigate efficacy and safety of tisagenlecleucel as CAR-T cell therapy in patients with blood cancers (B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma). Actemra was administered as monotherapy or combination therapy with corticosteroids or other treatments to patients with severe CRS.

Prescribing Information *The underlined parts were newly added.
[Indications]

The following diseases that have not responded sufficiently to existing therapies:
rheumatoid arthritis (including inhibition of structural joint damage), polyarticular-course juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis
Improvement of symptoms and laboratory findings associated with Castleman’s disease (high C-reactive protein, high fibrinogen, elevated erythrocyte sedimentation rate, low hemoglobin, low albumin, and general malaise), excluding those for whom lymphadenectomy is indicated.
Cytokine release syndrome induced by tumor-specific T cell infusion therapy
[Dosage and Administration]

Rheumatoid arthritis and polyarticular-course juvenile idiopathic arthritis
The recommended dose of tocilizumab (genetical recombination) is 8 mg/kg as a single intravenous injection administered at 4-week intervals.
Systemic juvenile idiopathic arthritis and Castleman’s disease
The recommended dose of tocilizumab (genetical recombination) is 8 mg/kg as a single intravenous injection administered at 2-week intervals. The dosing interval can be shortened to a minimum of 1 week depending on patients’ disease symptoms.
Cytokine release syndrome
The recommended dose of tocilizumab (genetical recombination) is 8 mg/kg in patients weighing at least 30 kg and 12 mg/kg in patients weighing less than 30 kg, as a single intravenous injection.
About Tumor-Specific T Cell Infusion Therapy
Tumor-specific T cell infusion therapy is an immunotherapy to enhance immune response to target tumor cells and to inject extracorporeally amplified T-cells expressing a specific receptor to recognize cancer cells. Tumor-specific T cell infusion therapies currently in development are chimeric antigen receptor (CAR)-T cell therapy and T cell receptor (TCR)-T cell therapy.

About Cytokine Release Syndrome
CRS is induced by the release of a large amount of cytokines in association with excessive immune response, and results in an extreme elevation of cytokine concentration in the blood.* CRS is an adverse reaction relatively common in CAR-T cell therapy, and many patients show mild to moderate influenza-like symptoms (pyrexia, nausea and chills, myalgia, etc.). However, severe hypotension, tachycardia, dyspnea, and others may be induced in some patients, and the symptoms may progress rapidly and may lead to death.

* Lee DW, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014 Jul 10; 124(2): 188-95.

On March 25, 2019 Oasmia Pharmaceutical AB (NASDAQ: OASM) reported that the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of a type II variation application to add efficacy data to the Apealea product information (Press release, Oasmia, MAR 25, 2019, View Source [SID1234556567]).

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The marketing authorisation approval for Apealea in the EEA was based on the phase III pivotal study OAS‑07OVA. The study was conducted on 789 randomized patients with relapse of ovarian cancer disease that were treated with paclitaxel in combination with carboplatin. The results of the subpopulation analysis of the patients corresponding to the approved indication, i.e patients experiencing their first relapse, were based on 301 patients (Apealea arm) and 298 patients (Comparator arm).

The positive opinion of the application allows the product information to present all available efficacy data for Apealea for the approved indication in addition to the data describing the entire population. This change may be implemented after completion of the review process of the translation into all EU languages (and Norwegian and Icelandic) by the end of April 2019.

– This provides complete transparency to the physicians, as well as patients, regarding differences in efficacy between Apealea and solvent-based paclitaxel, says Mikael Asp, CEO

Information on subgroup analysis by relapse:

Subgroup analyses were conducted to investigate efficacy by relapse (first and second) in the per protocol (PP) and the intention-to-treat (ITT) populations. Progression free survival (PFS) and overall survival (OS) results in the PP population are presented in the tables below. In the intention-to-treat population, the hazard ratios (HR) for PFS in the subgroups of patients with first relapse and second relapse were 0.80 (95% confidence interval (CI): 0.66;0.97) and 1.04 (95% CI: 0.74;1.47), respectively. The hazard ratios for OS in patients with first and second relapse were 0.98 (95% CI: 0.79;1.21) and 1.18 (95% CI: 0.79;1.75), respectively. Thus, the results in the subgroup of patients with first relapse are consistent with the results in the overall population and in addition, there was an indication of PFS benefit for Apealea.

About epithelial ovarian cancer

Ovarian cancer is the seventh most common cancer in women. Approximately 239,000 women are annually diagnosed with ovarian cancer globally and 152,000 dies from the disease. Epithelial ovarian cancer is the most common form and accounts for about 90% of ovarian cancers. The disease is often diagnosed at an advanced staged since it has no symptoms at early stages. The five-year survival rate (i.e. survival of patients with ovarian cancer compared to survival in the general population at the same age) for ovarian cancer has been estimated to 38% in Europe. During 2018, approximately 68,000 women will be diagnosed with ovarian cancer in Europe and 45,000 are predicted to die from the disease. Carboplatin and paclitaxel are common chemotherapy drugs for treatment of ovarian cancer and are often used in combination.

About Apealea

Apealea is a Cremophor- and albumin-free formulation of the well-known cytostatic paclitaxel combined with Oasmia’s excipient technology XR17. Paclitaxel is one of the most widely used anticancer substances and is included in the standard treatment of a variety of cancers such as lung cancer, breast cancer and ovarian cancer. Apealea consists of a freeze-dried powder, which is dissolved in conventional solutions for infusion.

On March 25, 2019 ExCellThera Inc., a clinical stage biotechnology company delivering molecules and bioengineering solutions to expand stem and immune cells for therapeutic use, reported that its lead technology, ECT-001, will be used as part of two new clinical trials in patients with high-risk leukemia (Press release, ExCellThera, MAR 25, 2019, View Source [SID1234535179]). The announcement follows the recent clearance of the company’s Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) and of a clinical trial application by Health Canada, in each case for the use of ECT-001 to treat patients with high-risk leukemia and myelodysplasia. The US-based study will be conducted at the Fred Hutchinson Cancer Centre in Seattle, Washington, with the Canadian study principally taking place at the Hôpital Maisonneuve-Rosemont in Montreal, Quebec.

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Leukemia is a cancer that begins in blood stem cells and can develop very quickly. It results in the over-production of abnormal cells, which crowd out healthy blood cells and leave the patient tired, short of breath and prone to bleeding, bruising and infection. Current treatment may include chemotherapy, radiation and a hematopoietic (blood) stem cell transplant.

"Blood stem cell transplants present a life-saving option for some patients; however, they can lead to life-threatening complications," said Dr. Guy Sauvageau, CEO and founder of ExCellThera. "ECT-001 expanded blood transplants are reengineered grafts with higher quantities of stem and immune cells. Our clinical data thus far show the grafts greatly reduce the risks of post-transplant complications, including chronic graft-versus-host-disease, infection and disease relapse, resulting in better overall well-being for patients."

The two new studies are designed to be complementary and will each enrol up to 20 patients, representing geographically distinct populations. Primary endpoints include relapse free survival and incidence of transplant related mortality. Secondary endpoints include graft-versus-host disease and other infectious complications.

ExCellThera plans to initiate additional trials, including a Phase III pivotal trial in the United States and Canada, in the coming months. In December 2018, ECT-001 received FDA orphan drug designation for the prevention of graft-versus-host disease.

About ECT-001
The ECT-001 technology is a combination of a small molecule, UM171, and an optimized culture system. The technology, capable of expanding the number of stem and immune cells exponentially in as little as seven days, is used in novel curative blood transplant therapies for patients with blood cancers, allowing more rapid engraftment, greatly reduced incidence of transplant-related mortality, low risk of chronic graft-versus-host disease and low risk of relapse, resulting in better outcomes for patients.

On March 25, 2019 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), ("Onxeo" or "the Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage response (DDR) in oncology, in particular against rare or resistant cancers, reported that details on the presentation of data from five studies supporting the company’s lead drug candidate, AsiDNA, in poster sessions at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held March 29 – April 3, 2019, in Atlanta, GA, USA (Press release, Onxeo, MAR 25, 2019, View Source [SID1234534652]).

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Françoise Bono, PhD, Chief Scientific Officer, commented: "We are very pleased to have five studies accepted and presented at the prominent AACR (Free AACR Whitepaper) meeting as it reflects the interest, the quality and the diversity of our current translational research on AsiDNA. Through these data, we further demonstrate the uniqueness of our lead compound in terms of mechanism of action and its related unique properties, especially on preventing the occurrence of resistance to treatment, one of the major issues in oncology today. All these data complement and reinforce our rationale for the continued clinical development of AsiDNA expected to start in the coming weeks, now that we have identified the active doses that trigger target engagement and confirmed the favorable safety profile in our phase I DRIIV study. We look forward to presenting and discussing our very exciting findings during the conference."