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U.S. FDA Approves YONDELIS® (trabectedin) for Soft Tissue Sarcoma (Liposarcoma or Leiomyosarcoma)

On October 23, 2015 PharmaMar reported that its licensing partner, Janssen Biotech, Inc. received marketing approval for YONDELIS (trabectedin) by the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic liposarcoma (LPS) or leiomyosarcoma (LMS) who have received a prior anthracycline-containing regimen (Press release, PharmaMar, OCT 23, 2015, View Source [SID:1234507897]). LPS and LMS are among the most common types of soft tissue sarcoma and this is the first treatment to be specifically approved for LPS in the U.S.

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The approval was based on the clinical efficacy and safety data from a recently published Phase 3, randomized, open-label, controlled study, ET743-SAR-3007, which evaluated YONDELIS versus dacarbazine in this patient population. This pivotal trial confirmed the results of previous clinical studies and provides strong evidence of the clinical benefit of trabectedin.

"Since YONDELIS was first approved in Europe in 2007 approximately 50,000 patients in 80 countries have benefited from this therapy across all indications," says Luis Mora, Managing Director, PharmaMar, who added that "the approval in the U.S. will allow more patients with this disease to have access to a drug that will address an unmet medical need."

For the approval of YONDELIS in the U.S., PharmaMar will receive the appropriate milestone from Janssen Products, LP.

About Liposarcoma (LPS) or Leiomyosarcoma (LMS)
LPS and LMS represent approximately 35% of all STS cases, of which there are 50 subtypes. LMS is an aggressive type of STS that occurs in smooth muscles, such as those in the uterus, abdominal cavity, or blood vessels. LPS originates in fat cells and most commonly occurs in the thigh and abdominal cavity, though it can occur in fat cells in any part of the body.

About YONDELIS (trabectedin)
YONDELIS (trabectedin) is a synthetically produced anti-tumor agent, originally derived from the sea squirt, Ecteinascidia turbinata. It works by targeting the transcription machinery and impairing DNA repair in cancer cells, thus inducing tumor cell death. It is approved in 80 countries in North America, Europe, South America and Asia. Indications vary by country and include the treatment of advanced soft tissue sarcomas and relapsed ovarian cancer in combination with DOXIL/CAELYX (doxorubicin HCl
liposome injection). Under a licensing agreement with PharmaMar, Janssen Products, L.P. has the rights to develop and sell YONDELIS globally except in Europe, where PharmaMar holds the rights, and in Japan, where PharmaMar has granted a license to Taiho Pharmaceutical Co., Ltd.

CBMG to Present Phase IIa Results from CAR-T CD20 Immuno-Oncology

On October 23, 2015 Cellular Biomedicine Group Inc. (NASDAQ: CBMG) ("CBMG" or the "Company"), a biomedicine firm engaged in the development of effective treatments for degenerative and cancerous diseases, reported that it would provide a meaningful update on a Phase IIa Trial of it’s CD20 Chimeric Antigen Receptor T-cell (CAR-T) therapy in Advanced, Refractory or Relapsed Diffuse Large B-Cell Lymphoma (DLBCL) at the upcoming 4th International Conference on Translational Medicine to be held on October 26-28, 2015 in Baltimore, Maryland, USA (Press release, Cellular Biomedicine Group, OCT 23, 2015, View Source [SID:1234507846]).

Title: Treatment of CD20-directed chimeric antigen receptor-modified T cells in patients with relapsed or refractory B-cell Non-Hodgkin’s lymphoma: An early Phase IIa trial report
Scientific Program: October 26, 2015 16:15-16:40 EDT
Location: DoubleTree by Hilton Hotel Baltimore – BWI Airport, Chesapeake Hall
Presenter: Yihong Yao, Ph.D., Chief Scientific Officer, Cellular Biomedicine Group

Full details of the presented data will be available on the Company’s website following the presentation.

Acceleron Highlights Phase 3 Studies, New Clinical Results and Research Strategies at Research and Development Day Event

On October 23, 2015 Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutic candidates that regulate cellular growth and repair, reported the phase 3 clinical trial designs for the luspatercept program in myelodysplastic syndromes ("MEDALIST" study) and beta-thalassemia ("BELIEVE" study), phase 1 preliminary results from the ACE-083 program, and its new IntelliTrap drug discovery platform (Press release, Acceleron Pharma, OCT 23, 2015, View Source [SID:1234507775]).

"We are extremely excited to present the plans for Acceleron’s first phase 3 clinical trials, the unprecedented increases in muscle mass demonstrated in the ACE-083 phase 1 clinical trial supporting its advancement into phase 2 trials next year and our new IntelliTrap drug discovery platform which is already generating promising new therapeutic candidates such as ACE-2494," said John Knopf, Ph.D., Chief Executive Officer of Acceleron. "Acceleron is making great strides across its entire pipeline from our late stage phase 3 programs to our highly productive discovery organization and I am proud of the tremendous progress we are making."

Luspatercept Phase 3 Clinical Trials in Myelodysplastic Syndromes (MDS) and Beta-Thalassemia

Acceleron announced that the phase 3 MDS trial will be a double-blind, randomized, placebo-controlled study of luspatercept in 210 very low to intermediate risk MDS patients (the "MEDALIST" study). The primary endpoint is the proportion of patients that become red blood cell transfusion independent (≥ 8 weeks) during the first 24 weeks of the study.

The phase 3 beta-thalassemia trial will be a double-blind, randomized, placebo-controlled study of luspatercept in 300 regularly transfused beta-thalassemia patients (the "BELIEVE" study). The primary endpoint is the proportion of patients with ≥ 33% reduction in transfusion burden from weeks 13 to 24 compared to the 12 weeks preceding treatment.

Both the MEDALIST and BELIEVE studies are planned to begin by the end of the year.

ACE-083 Phase 1 Preliminary Results

Acceleron reported positive top-line data from the phase 1 randomized, double-blind, placebo-controlled, dose-ranging study in healthy volunteers. ACE-083 is designed to selectively increase muscle mass and strength in the muscles in which the drug is administered. The results showed a dose dependent increase in muscle volume, assessed by MRI, with the highest dose level generating a 14% increase in volume of the injected muscle, the rectus femoris, in the thigh.

Based on these exciting results, Acceleron announced it intends to advance ACE-083 into a phase 2 clinical trial in patients with facioscapulohumeral muscular dystrophy in mid-2016.

IntelliTrap Drug Discovery Platform

Acceleron introduced its new IntelliTrap drug discovery platform from which it is creating a large and diverse library of new, selective therapeutic candidates targeting the TGF-beta superfamily. This platform has already generated several new therapeutic candidates including ACE-2494, a systemic muscle therapeutic and the first clinical candidate to emerge from this platform. Acceleron aims to initiate its first clinical trial of ACE-2494 by the end of 2016.

A replay of the live webcast of the Research and Development Day event will be accessible from the "Investors & Media" section of the company’s website, www.acceleronpharma.com.

FDA approves new therapy for certain types of advanced soft tissue sarcoma

On October 23, 2015 The U.S. Food and Drug Administration reported that it has approved Yondelis (trabectedin), a chemotherapy, for the treatment of specific soft tissue sarcomas (STS) – liposarcoma and leiomyosarcoma – that cannot be removed by surgery (unresectable) or is advanced (metastatic) (Press release, , OCT 23, 2015, View Source [SID:1234507774]). This treatment is approved for patients who previously received chemotherapy that contained anthracycline.

According to the National Cancer Institute, STS is a disease in which cancer cells form in the soft tissues of the body, including the muscles, tendons, fat, blood vessels, lymph vessels, nerves and tissues around joints. Liposarcoma and leiomyosarcoma are specific types of STS that occur in fat cells (liposarcoma) or smooth muscle cells (leiomyosarcoma). STS can form almost anywhere in the body, but is most common in the head, neck, arms, legs, trunk and abdomen. In 2014, an estimated 12,000 cases of STS were diagnosed in the United States.

"The treatment of advanced or metastatic soft tissue sarcoma represents a difficult challenge with few effective therapeutic choices available for patients," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. "Today’s approval of Yondelis provides a treatment option for advanced or metastatic liposarcoma and leiomyosarcoma."

The effectiveness and safety of Yondelis were demonstrated in 518 clinical trial participants with metastatic or recurrent leiomyosarcoma or liposarcoma. Participants were randomly assigned to receive either Yondelis (345 patients) or dacarbazine (173 patients), another chemotherapy drug. Participants who received Yondelis experienced a delay in the growth of their tumor (progression-free survival), which occurred on average about 4.2 months after starting treatment, compared to participants assigned to dacarbazine, whose disease progressed an average of 1.5 months after starting treatment.

The most common side effects among participants who received Yondelis were nausea, fatigue, vomiting, diarrhea, constipation, decreased appetite, shortness of breath (dyspnea), headache, tissue swelling (peripheral edema), a decrease in infection-fighting white blood cells (neutropenia), low blood platelet counts (thrombocytopenia), low red blood cell count (anemia), elevated liver enzymes and decreases in albumin, a protein found in blood.

Yondelis carries a warning alerting health care providers of the risk of severe and fatal blood infections (neutropenic sepsis), muscle tissue breakdown (rhabdomyolysis), liver damage (hepatotoxicity), leakage around the vein or catheter (extravasation), tissue necrosis (breakdown) and heart failure (cardiomyopathy). Patients with known hypersensitivity to trabectedin, a drug used to treat cancer, should not take Yondelis.

Health care providers are also encouraged to advise women of potential risks to a developing fetus when taking Yondelis. Women who are taking Yondelis should not breastfeed.

Yondelis is marketed by Janssen Products of Raritan, New Jersey.

U.S. FDA Approves YONDELIS® (trabectedin) for the Treatment of Patients with Unresectable or Metastatic Liposarcoma or Leiomyosarcoma, Two Common Subtypes of Soft Tissue Sarcoma

On October 23, 2015 Janssen Biotech reported that the U.S. Food and Drug Administration (FDA) has approved YONDELIS (trabectedin) for the treatment of patients with unresectable (unable to be removed with surgery) or metastatic liposarcoma (LPS) or leiomyosarcoma (LMS) who received a prior anthracycline-containing regimen (Press release, Johnson & Johnson, OCT 23, 2015, View Source [SID:1234507776]). The approval was based on recently published clinical efficacy and safety data from the Phase 3, randomized, open-label, controlled study (ET743-SAR-3007), which evaluated YONDELIS versus the chemotherapy agent dacarbazine, in patients with unresectable or metastatic LPS or LMS previously treated with an anthracycline and at least one additional chemotherapy regimen.

While approved for both LPS and LMS, YONDELIS is the first treatment to be specifically approved for LPS in the U.S.

"Our academic teams are dedicated to finding new treatments with scientific merit and the promise to improve outcomes for patients with sarcomas. Today’s announcement marks a meaningful event built upon years of research, offering new hope for people living with two of the most prevalent subtypes of this serious disease – liposarcoma and leiomyosarcoma – where there are limited available alternatives," said George D. Demetri, M.D.,† Director of the Ludwig Center at Harvard and Director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute, and principal investigator of the Phase 3 registration trial. "In the clinical trial, YONDELIS significantly increased progression free survival compared to dacarbazine; this is an important endpoint for these patients, in whom rapid worsening of the disease can lead to worse symptoms and life-threatening situations."

The pivotal Phase 3 study enrolled over 500 patients and demonstrated an improvement in progression free survival (PFS) for patients treated with YONDELIS. The median PFS among the YONDELIS treatment group was 4.2 months (n=345; 95% confidence interval (CI): 3.0 – 4.8 months), while the median PFS in the dacarbazine treatment group was 1.5 months (n=173; 95% CI: 1.5 – 2.6 months), representing a 45% reduction in the risk of disease progression or death with YONDELIS (HR=0.55; 95% CI: 0.44 – 0.70; p<0.001). The final analysis of overall survival (OS) demonstrated a median OS of 13.7 months for the YONDELIS arm and 13.1 months in dacarbazine arm, which was not significant (HR=0.93; 95% CI: 0.75, 1.15; p=0.49).

LPS and LMS are subtypes of soft tissue sarcoma (STS) and represent more than 35% of all STS cases.2 LMS is an aggressive type of STS where smooth muscle cells become cancerous. LMS typically occurs in the uterus, abdominal cavity or blood vessels but can also arise in any part of the body.3, 4 LPS is comprised of several subtypes and develops in fat cells that become cancerous in any part of the body.5, 6

Since YONDELIS was first approved in Europe in 2007, approximately 50,000 patients in close to 80 countries have benefited from this therapy across all indications. "The U.S. approval for YONDELIS exemplifies our commitment to improving the health of people living with cancer and addressing unmet needs," said Roland Knoblauch, M.D., Ph.D., Clinical Leader, YONDELIS, Janssen Research & Development, LLC. "We are proud that our Phase 3 study is the largest ever conducted in this patient population and we’re delighted that patients in the U.S. can now benefit from the treatment."

The safety profile of YONDELIS in the Phase 3 study was consistent with previous clinical studies. The most serious risks associated with YONDELIS are neutropenic sepsis (severe infections due to decreased white blood cells), rhabdomyolysis (severe muscle problems), cardiomyopathy (heart muscle problems, including heart failure), hepatotoxicity (liver problems, including liver failure), anaphylaxis, and extravasation (leakage of YONDELIS out of the vein during infusion) leading to tissue necrosis (tissue cell damage or death) and embryofetal toxicity. Among the 378 patients who received at least one dose of YONDELIS in the randomized trial, the most common (≥20%) adverse reactions were nausea (75%), fatigue (69%), vomiting (46%), constipation (37%), decreased appetite (37%), diarrhea (35%), peripheral edema (28%), dyspnea (25%) and headache (25%). The most common (≥5%) Grade 3-4 laboratory abnormalities were neutropenia (43%), increased alanine transaminase (ALT) (31%), thrombocytopenia (21%), anemia (19%), increased aspartate aminotransferase (AST) (17%) and increased creatine phosphokinase (6.4%).

The recommended dose of YONDELIS is 1.5 mg/m2 administered as an intravenous infusion over 24 hours through a central venous line every 21 days (3 weeks) until disease progression or unacceptable toxicity in patients with normal bilirubin and AST or ALT, less than or equal to 2.5 times the upper limit of normal.