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Boehringer Ingelheim's Breakthrough Cancer Drug Demonstrates Promising Results in a Mid-Stage Study

Boehringer Ingelheim

German drugmaker Boehringer Ingelheim recently announced that its breakthrough treatment for a rare form of leukemia prolonged survival and beat out chemotherapy in a mid-stage study.

The company said that results from a Phase II study showed that patients with previously untreated acute myeloid leukemia (AML) aged 65 or older and ineligible for intensive remission induction therapy, lived longer when treated with volasertib combined with low dose cytarabine (LDAC) compared to LDAC alone. Data on overall survival showed that the addition of volasertib to LDAC increased the percentage of older AML patients who achieved remission. Results from the Phase II study were published in the American Society of Hematology journal, Blood.

AML is an aggressive and devastating blood cancer. Despite being a rare disease, AML is one of the most common leukemias in adults and predominantly affects people over the age of 60. Currently, the established approach to treat younger AML patients is an intensive chemotherapy regimen, called intensive induction therapy. However, many older patients cannot tolerate these chemotherapy doses, and have very limited treatment options and poor prognosis.

“These clinical trial results that evaluated volasertib in combination with a lower intensity chemotherapy are important and have informed future research for this rare disease, where new treatment options are greatly needed,” said Prof. Döhner from the Department of Internal Medicine III of the University Hospital Ulm and principal investigator of the Phase II trial.

The Phase II trial evaluated 87 patients with a median age of 75 years. Results showed that patients treated with volasertib in combination with LDAC had a median overall survival (OS) of 8 months compared to 5.2 months in patients treated with LDAC alone. Additionally, data showed that the cancer was absent in 31 percent of patients after being treated with volasertib with LDAC compared to 13.3 percent of patients who were treated with LDAC alone. The most common non-hematological adverse events reported in patients receiving volasertib were decreased white blood cells with fever and infections and gastrointestinal side effects. These side effects were clinically manageable and were expected, due to volasertib’s mechanism of action.

Volasertib inhibits enzymes called Polo-like kinases (Plks) to spur cancer cell death. The drug’s inhibition of Plk1 activity should block the extremely high cell division that is a characteristic of AML, which may result in cancer regression. The US Food and Drug Administration (FDA) granted volasertib Breakthrough Therapy Designation in 2013 and Orphan Drug Designation in 2014. Boehringer Ingelheim is currently evaluating the drug in combination with LDAC in the Phase III POLO-AML-2 clinical trial for treatment of AML.

“As with other rare and life threatening diseases, the need for new treatment options in AML is very high. Boehringer Ingelheim is committed to research in areas of unmet medical need, including those in rare diseases,” said Prof. Klaus Dugi, Chief Medical Officer, Boehringer Ingelheim. “We are pleased to see that volasertib has shown promising overall survival results in this clinical trial and we are optimistic that the drug will further demonstrate its potential benefit in this rare disease in the ongoing Phase III study.”

Source: Boehringer Ingelheim Pharmaceuticals, Inc.

Last updated: 7/9/14; 11:35am EST

CASI Pharmaceuticals' Liver Cancer Drug Receives Orphan Drug Designation

CASI Pharmaceuticals

Today, CASI Pharmaceuticals, Inc. announced that the Food and Drug Administration (FDA) has granted Orphan Drug designation to its investigational hepatocellular carcinoma (HCC) drug.

The agency granted orphan drug status to CASI’s ENMD-2076, an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. The FDA grants orphan drug designation to therapeutics treating rare diseases, affecting less than 200,000 people in the US.

ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. Aurora kinases are key regulators of mitosis and are often overexpressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases, which have been shown to play key roles in the pathology of various cancers.

HCC is the most common form of liver cancer, accounting for approximately 75 percent of all liver cancers. The disease starts in the main type of liver cells, known as hepatocellular cells. Most HCC cases are a result of infection with hepatitis B or C, or cirrhosis of the liver caused by alcoholism.

“We are pleased with the Orphan Drug designation as it confirms our belief in the versatility of ENMD-2076 as a promising treatment for HCC, and for other tumor types that we are currently evaluating in the clinic. Orphan drug status also enhances the commercial value of ENMD-2076 to treat HCC, a disease which is difficult to treat. We are finalizing our next steps for ENMD-2076 in HCC and/or fibrolamellar carcinoma, a subset of HCC and for which there is no treatment available and look forward to advancing our overall development plan for ENMD-2076,” said Dr. Ken Ren, Chief Executive Officer of CASI.

The FDA has also granted Orphan Drug designation to ENMD-2076 for the treatment of ovarian cancer, multiple myeloma and acute myeloid leukemia. The drug has shown promise in early-stage clinical trials in solid tumor cancers including ovarian, breast, liver, renal and sarcoma, as well as in leukemia and multiple myeloma.

Shares rose more than three percent in premarket trading.

Source: CASI Pharmaceuticals, Inc.

Last updated: 7/7/14; 3:10pm EST

Novartis' Personalized Cell Therapy Awarded Breakthrough Therapy Designation


The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to Novartis AG’s investigational chimeric antigen receptor (CAR) therapy for treatment of leukemia.

The agency awarded the status to Novartis’ CTL019 for the treatment of pediatric and adult patients with relapsed/refractory acute lymphoblastic leukemia (r/r ALL). This marks Novartis’ fifth Breakthrough Therapy designation from the FDA.

“This Breakthrough Therapy designation underscores the potential of CTL019 as a life-saving therapy for patients with relapsed/refractory ALL, who are in desperate need of new treatment options,” said David Epstein, Division Head, Novartis Pharmaceuticals. “Novartis welcomes increased dialogue with the FDA and a potentially expedited review to streamline the development of CTL019 and hopefully bring this promising therapy to patients as quickly as possible.”

In 2012, Novartis and the University of Pennsylvania (Penn) entered into an exclusive global research and licensing agreement to further study and commercialize novel cellular immunotherapies using CAR technologies. CTL019 is a personalized immunotherapy that was developed at the University of Pennsylvania and is the first personalized cellular therapy for the treatment of cancer to receive Breakthrough Therapy designation. In early-stage trials at the Hospital of the University of Pennsylvania, 89 percent of ALL patients who were not responding to conventional therapies went into complete remission after receiving CTL019.

“Our early findings reveal tremendous promise for a desperate group of patients, many of whom may have been able to return to their normal lives at school and work after receiving this new, personalized immunotherapy,” said the Penn research team’s leader, Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of Translational Research in the Abramson Cancer Center of the University of Pennsylvania.

Novartis holds the worldwide rights to CARs developed through its collaboration with Penn for all cancer indications, including CTL019. The University of Pennsylvania’s Perelman School of Medicine submitted the filing and is currently conducting the CTL019 Phase I/II clinical trials. The drug works by engineering a patient’s own T-cells to hunt and attack cancer cells that express specific proteins, called CD19.

ALL is the most common cancer diagnosed in children, accounting for 25 percent of cancer diagnoses among children younger than 15 years. Additionally, the disease can occur in adults. In ALL patients, the bone marrow makes too many abnormal white blood cells, also known as lymphocytes. If the disease is not treated, it typically progresses quickly and can be fatal within a few months.

Sources: Novartis AG; Penn Medicine

Last updated: 7/7/14; 2:10pm EST 

Japanese Regulators Approve the First PD-1 Drug for Treatment of Melanoma

Ono Pharmaceutical

Ono Pharmaceutical Co. has become the first company in the world to receive approval for a programmed death-1 (PD-1) checkpoint inhibitor.

The company recently announced that it has received manufacturing and marketing approval in Japan for the human anti-human PD-1 monoclonal antibody nivolumab for the treatment of unresectable melanoma. Nivolumab is now approved for use in patients with melanoma in Japan, marketed as Opdivo. Ono Pharmaceutical picked up Japanese rights to the drug in 2005 under a collaboration deal with Medarex, which was acquired by Bristol-Myers Squibb (BMS) in 2009. Outside of Japan, Korea and Taiwan, BMS owns rights to nivolumab.  

Ono Pharmaceutical said that it will provide Opdivo to patients free of charge as soon as it is ready in order to help individuals who need early treatment with the drug. Currently, only chemotherapy dacarbazine is available as standard drug therapy for the treatment of advanced melanoma in Japan. Opdivo will be offered free of charge until the product is listed on the national health insurance (NHI) price list.

Due to the limited number of patients treated with the drug in Japanese clinical trials, Ono Pharmaceutical is required to perform a post-marketing use-results survey covering all-case surveillance until data on a certain minimum number of patients have been collected.

“We are delighted to obtain a manufacturing and marketing approval as a drug targeting PD-1, which receives a lot of attention in tumor immunity, for the first time in the world,” said Gyo Sagara, the President and Representative Director of Ono. “ONO would like to obtain approvals for additional indications on ongoing development for other cancers to bring many patients Opdivo as soon as possible.”

PD-1 is a receptor expressed on the surface of lymphocytes and plays a role in a regulatory pathway that suppresses activated lymphocytes in the body. Evidence suggests that cancer cells use this pathway to escape from immune responses. In addition to melanoma, nivolumab has demonstrated efficacy in several other tumor types and is currently being tested by BMS in several different studies. Nivolumab was granted breakthrough therapy designation for the treatment of patients with Hodgkin’s lymphoma after failure of autologous stem cell transplant and brentuximab.

Source: Ono Pharmaceutical Co., Ltd.

Last updated: 7/7/14; 12:35pm EST

FDA Provides Early Approval to Spectrum's Rare Lymphoma Drug

Spectrum Pharmaceuticals

Spectrum Pharmaceuticals’ blood cancer drug was granted accelerated approval by the US Food and Drug Administration (FDA).

The agency granted accelerated approval of Spectrum’s Beleodaq (belinostat) for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), a rare and aggressive form of non-Hodgkin’s Lymphomas (NHL). The accelerated approval is based on Tumor Response Rate and Duration of Response.

The approval of Beleodaq, a histone deacetylase inhibitor (HDAC), comes more than a month ahead of the PDUFA date of August 9th. The news sent Spectrum’s shares up more than six percent.

“This FDA approval enables us to help address this unmet medical need, and provide a new treatment option for patients with this difficult-to-treat and ultimately fatal disease,” said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. “First with Folotyn (pralatrexate injection) and now with Beleodaq, we are very proud to be able to offer patients and clinicians two approved treatment options for R/R PTCL, and be a leader in the treatment of T-cell lymphomas. We will be able to effectively leverage our existing Hematology clinical and sales infrastructure to expedite the launch of Beleodaq. Now with a total of five approved Hematology/Oncology drugs and a strong and maturing development pipeline, Spectrum is well positioned for continued future growth.”

The agency approved Beleodaq based on data from the BELIEF study, consisting of 120 evaluable patients, refractory to or who had failed at least one prior systemic therapy. The study’s primary efficacy endpoint was overall response rate (ORR). In the study, Beleodaq was shown to have an ORR of 25.8 percent with a high response rate (45.5%) in patients with Angioimmunoblastic T-cell Lymphoma. The most common side effects were nausea, fatigue, fever, low red blood cells and vomiting.

PTCL comprises of a group of rare and aggressive NHLs that develop from mature T-cells. PTCL accounts for approximately 10 – 15 percent of all NHL cases in the US. Generally, PTCL patients have a poor prognosis with a low response rate to available treatment options, and commonly experience repeated treatment failures until individuals become resistant to the drug or die.

“Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin’s lymphoma with no accepted standard of care,” said Owen A. O’Connor, MD, PhD, Director of Lymphoid Malignancies, Professor of Medicine and Experimental Therapeutics at Columbia Medical Center, New York Presbyterian Medical Center, one of the lead investigators in the BELIEF study. “Relapse is common after initial treatment, and there are limited options for patients in 2nd line and beyond. Histerone deacetylase inhibitors have emerged as one promising class of drugs for patients faced with this disease. One interesting observation in the study was the tolerability of Beleodaq in these heavily treated patients. Beleodaq was associated with myelosuppression with an overall rate of anemia 32%, thrombocytopenia of 16.3% and neutropenia of 9.3% and Grade 3/4 adverse reactions were reported in 10.9%, 7.0% and 6.2% of patients, respectively. The associated severity of hematologic toxicities may prove to be useful in previously treated patients who have poor bone marrow reserve.”

The approval triggered a milestone payment of $25 million in cash to Spectrum’s partner Topotarget of Denmark.

Source: Spectrum Pharmaceuticals, Inc.

Last updated: 7/7/14; 11:30am EST