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Oncology

AbbVie's Investigational Brain Tumor Drug Receives Orphan Drug Designation from US and European Regulators

AbbVie

The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have granted orphan drug designation to AbbVie’s investigational brain tumor drug.

The drug, ABT-414, is being evaluated for safety and efficacy in patients with glioblastoma multiforme, the most common and most aggressive type of malignant primary brain tumor.

“The orphan drug designation is an important regulatory advancement as we further our development in recurrent glioblastoma multiforme, a disease that is uniformly fatal with limited treatment options,” said Gary Gordon, MD, vice president, oncology clinical development, AbbVie. “We are pleased to continue developing ABT-414 in Phase II clinical trials in patients with glioblastoma multiforme based on the results of our Phase I program.”

Glioblastoma multiforme is the most common and most aggressive type of malignant primary brain tumor. Before diagnosis, most patients experience a serious symptom of glioblastoma multiforme, such as seizure. Most patients succumb to the disease about 15 months after being diagnosed, since no long-term treatments are currently available. Standard treatment for the disease is surgical resection, radiotherapy and concomitant adjunctive chemotherapy. Each year in the US and Europe, two to three out of every 100,000 people are diagnosed with glioblastoma multiforme, which has a five year survival rate of approximately four percent.

AbbVie’s ABT-414 is an investigational anti-epidermal growth factor receptor antibody drug conjugate (ADC) being evaluated for the treatment of patients with various cancer and tumor types. The drug is designed to be stable in the bloodstream and only release the potent cytotoxic agent once inside targeted cancer cells. In addition to glioblastoma multiforme, ABT-414 is in clinical trials for the treatment of patients with squamous cell tumors.

Results from a Phase I clinical program evaluating ABT-414 in patients with recurrent or unresectable glioblastoma multiforme were presented at the 50th American Society of Clinical Oncology (ASCO) meeting in Chicago earlier this year.

Source: AbbVie Inc.

Last updated: 8/4/14; 3:45pm EST

Ziopharm Grants Solasia Exclusive Worldwide Rights to Anticancer Drug Zinapar

Ziopharm Oncology

US drug developer Ziopharm Oncology and Japan’s Solasia Pharma recently announced an amendment and restatement of their license and collaboration agreement for Ziopharm’s anticancer drug darinaparsin (Zinapar or ZIO-101). 

The amendment is expanding on a deal made back in March of 2011, under which Ziopharm granted Solasia exclusive rights to darinaparsin in the territories of Japan, China, Hong Kong, Macau, Republic of Korea, Taiwan, Singapore, Australia, New Zealand Malaysia, Indonesia, Philippines and Thailand.

The new deal grants Solasia an exclusive worldwide license agreement to develop and commercialize darinaparsin and related organoarsenic molecules in both intravenous and oral forms in all indications for human use. In exchange, Ziopharm will be eligible for up to $72.2 million from Solasia in development and sales-based milestones, a royalty on net sales of darinaparsin once commercialized, and a percentage of any sublicense revenues generated by Solasia.  Solasia will be responsible for development, manufacturing and commercialization costs for darinaparsin.

“As our strategic focus has shifted towards DNA therapeutics and immuno-oncology, Solasia, with whom Ziopharm has had a longstanding partnership, is the natural choice to advance the development of darinaparsin on a global basis,” said Ziopharm’s Chief Executive Officer Jonathan Lewis, MD, PhD. “Through a collaboration that began in 2011, Solasia has built a meaningful scientific and clinical value. Further, by expanding this agreement to all global territories, there exists now an additional strong incentive for Solasia to rapidly and strategically develop this potentially important product candidate in areas of unmet medical need in oncology.”

Darinaparsin is a novel mitochondrial-targeted agent (organoarsenic) being developed for the treatment of various hematologic and solid cancers. The drug has been granted Orphan Drug Designation in the US and EU for treatment of peripheral T-cell lymphoma (PTCL).

“Solasia stands to benefit greatly from the acquisition of exclusive global development and commercialization rights to darinaparsin from Ziopharm,” said Yoshihiro Arai, President and Representative Director of Salasia Pharma K.K. “Our initial Asian clinical studies with darinaparsin in the clinical setting of PTCL have been very exciting and encouraged us to expand our longstanding partnership with Ziopharm in order to maximize our opportunity with the darinaparsin program throughout the world. We presently plan to start pivotal clinical trials in Asia early in 2015.”

Source: Ziopharm Oncology, Inc.

Last updated: 8/4/14; 11:50am EST

Amgen's Multiple Myeloma Drug Meets its Primary Endpoint in a Late-Stage Trial

Amgen

Today, Amgen announced that its blood cancer drug helped patients live significantly longer without the disease worsening compared with standard treatment.

The company said that patients with relapsed multiple myeloma treated with Kyprolis (carfilzomib) in combination with Celgene’s Revlimid (lenalidomide) and low-dose dexamethasone (KRd) beat out Revlimid and KRd alone in a head-to-head Phase III study, meeting the primary endpoint of progression-free survival.

In Amgen and its subsidiary, Onyx Pharmaceuticals, Inc.’s, planned interim analysis, patients treated with injectable Kyprolis plus Revlimid and KRd demonstrated a median progression-free survival (PFS) of 26.3 months, compared to a median of 17.6 months in patients treated with Revlimid and KRd alone. The improvement in PFS was considered statistically significant. Following the announcement, Amgen’s shares rose as much as 4.3 percent in premarket trading.

In 2012, the US Food and Drug Administration (FDA) granted the drug accelerated approval for use in multiple myeloma, the second most common form of blood cancer, which has limited treatment options. The accelerated approval was based on positive data from initial trials. With accelerated approval, manufacturers are required to conduct larger trials to support initial findings.

Results from the Phase III study, known as ASPIRE, will be submitted for presentation at the upcoming 56th Annual Meeting of the American Society of Hematology later this year. Data from the secondary endpoint, overall survival (OS), are not yet mature. However, the analysis showed a trend in favor of KRd that did not reach statistical significance. No new safety signals were identified in the study to date.

“We are excited about these clinical results and the positive prospects they suggest for patients with multiple myeloma,” said Robert A. Bradway, chairman and chief executive officer of Amgen. “Our mission at Amgen is to serve patients by advancing medicines that address serious disease. Kyprolis is an important building block in our robust, differentiated pipeline.”

According to Amgen, results from the late-stage study form the basis for regulatory submissions throughout the world beginning in the first half of 2015. The data may support the conversion of accelerated approval to full approval and expand the current indication.

Amgen gained rights to Kyprolis in its $10.4 billion buyout of Onyx. When Amgen purchased Onyx last August, Kyprolis has been approved as a third-line therapy for patients who had already failed two treatments.

“In the treatment of patients with multiple myeloma, periods of remission become shorter following each treatment regimen, underscoring the need for new options. The results of the ASPIRE study demonstrate the Kyprolis can significantly extend the time patients live without their disease progressing,” said Pablo J. Cagnoni, MD, president, Onyx Pharmaceuticals, Inc. “The ability of the novel therapies to produce deep and durable responses may, one day, transform this uniformity fatal disease to one that is chronic and manageable.”

Source: Amgen

Last updated: 8/4/14; 10:45am EST

Scientists Discover Cause of Rare Childhood Cancer

RMS

Scientists have made a breakthrough in understanding the cause or Rhabdomyosarcoma (RMS), a rare childhood muscle cancer.

A collaborative effort from an international group of scientists has revealed for the first time the key role that a protein called Yap plays in triggering the disease. The discovery could lead to the development of improved drugs to treat RMS and other types of cancer in the future.

Findings from the study, led by scientists from Harvard University and involving experts from the University of Aberdeen, were published in the journal Cancer Cell.  

RMS is a very rare cancer, with around 60 and 350 new cases diagnosed in the UK and Europe/US respectively, each year. Most RMS tumors occur in children younger than ten years old. RMS tumors can arise almost anywhere, however the most common location for these tumors to develop are in the head and neck structures, accounting for nearly 40 percent of all cases.

“The current therapies for RMS, although relatively efficient, are aggressive and drastically alter the quality-of-life of the children who survive. Indeed, most of the survivors will suffer life-altering consequences ranging from loss of mobility and/or vision, to life-long hormone replacement therapies only to go through puberty and live a normal life,” said Dr. Annie Tremblay from Harvard University.

During normal muscle development, stem cells turn into developmental muscle cells called myoblasts. The myoblasts divide, before finally fusing together to form long muscle fibers in the body. The Yap protein is essential to this process, with the myoblasts experiencing a marked increase in its activity during the division stage. Once enough myoblasts are present, Yap gets turned off, allowing them to stop dividing and fuse together to form functional muscles.  

“We discovered that in cases of the disease, excessive activity of a protein called Yap causes muscle stem cells to permanently divide instead of stopping and becoming normal muscle tissue. Yap does that by inhibiting the activity of muscle determination proteins, which are key to the formation of muscle tissue. In contrast to normal muscle stem cells, the high Yap muscle stem cells fail to develop into normal muscle tissue and Rhabdomyosarcoma develops as a consequence.”

Researchers at the University of Aberdeen, the Swiss bioinformatics institute and the Institute of Cancer Research combined the results from animal models with histological and bioinformatical approaches using human RMS samples. They found that Yap is hyper-active in a large proportion of human RMS cases.

“Our identification of the Yap protein’s crucial role in the development of Rhabdomyosarcoma is the first step on the road towards understanding how we can target this rare disease,” said Dr. Henning Wackerhage. “Our work will now focus on how the Yap protein works in cancer and how its activity can be controlled. If we can achieve the inhibition of inhibit Yap locally in the tumors, we could cause the cancer to stop and regress by turning the RMS into normal muscle instead. This would most likely produce significantly fewer side effects than the current therapies.”

According to Dr. Wackerhage, since other research has shown that Yap is active in a variety of cancers, including liver and skin cancers, results of this study could enhance the global understanding of Yap’s role in cancer.

Source: University of Aberdeen

Last updated: 8/1/14; 2:00pm EST

Incyte Enters Immuno-Oncology Deal with Genentech

Incyte

Today, Incyte Corporation announced that it has partnered with Roche’s Genentech for a clinical trial evaluating the combination of two novel cancer immunotherapies.

The company said that it has entered into a clinical trial agreement with Genentech to evaluate the safety, tolerability and preliminary efficacy of the combination of Incyte’s oral indoleamine dioxygenase-1 (IDO1) inhibitor, INCB24360, and Genentech’s PD-L1 immune checkpoint inhibitor, MPDL3280A, in patients with non-small cell lung cancer (NSCLC).

Under the deal, Incyte and Genentech will collaborate on a non-exclusive basis to evaluate the combination. Unlike many of Roche’s previous collaboration deals, Incyte will be responsible for conducting the study and the companies will use the results to determine whether to continue clinical development of the combination. Financial details of the agreement were not disclosed.

Both INCB24360 and MPDL320A are part of the new class of cancer drugs known as immunotherapies, designed to utilize the body’s own immune system to fight cancer.

“This collaboration with Genentech is a further illustration of our desire to investigate the therapeutic value of our IDO1 inhibitor in multiple tumor types as rapidly as possible,” said Hervé Hoppenot, President and Chief Executive Officer of Incyte. “We believe the combination of INCB24360 with other novel immunotherapies represents a promising new approach to treating cancer, and research collaborations such as this have the potential to accelerate our understanding and support our goal of addressing the needs of patients with a wide range of cancers.”

In addition to Genentech, Incyte has entered into deals with Bristol-Myers Squibb, AstraZeneca’s biologics research and development arm MedImmune, and Merck for clinical trials combining Incyte’s IDO1 inhibitor with other cancer drugs.

Source: Incyte Corporation

Last updated: 7/30/14; 12:00pm EST