FDA Expands Approval of Imbruvica for Rare Blood Cancer

gYik8JVToday, the US Food and Drug Administration (FDA) announced that it has expanded approval of Johnson & Johnson and Pharmacyclics’ Imbruvica (ibrutinib) for a rare form of blood cancer.

The agency approved Imbruvica for patients with Waldenstrom’s macroglobulinemia (WM), a rare form of cancer that begins in the body’s immune system. WM is a type of non-Hodgkin lymphoma (NHL), which usually gets worse slowly over time and causes abnormal blood cells, called B lymphocytes (B-cells), to grow within the bone marrow, lymph nodes, liver and spleen. Additionally, in WM abnormal B-cells overproduce a protein known as immunoglobulin M or IgM (macroglobulin) that can lead to excess bleeding, problems with vision and with the nervous system.

Imbruvica was granted Breakthrough Therapy Designation for WM from US health regulators. In addition to WM, Imbruvica is approved for three other indications in the US, including patients with mantle cell lymphoma (MCL) who have received at least one prior therapy, chronic lymphocytic leukemia (CLL) patients who have received at least one prior therapy and CLL patients with 17p deletion.

The FDA’s decision to approve Imbruvica for treatment of WM is based on results from a 63-patient study, which showed that 62 percent of participants had their cancer shrink after treatment, with the duration of response ranging from 2.8 months to approximately 18.8 months.

“Since the first description of Waldenstrom’s macroglobulinemia more than 70 years ago, there has been no approved treatment for this cancer. Rather, doctors relied on therapies borrowed from similar cancers to treat these patients. I am truly grateful to the FDA for their work and dedication of scientists and clinicians at various leading medical centers who diligently worked on the clinical trial that supports Imbruvica as a safe and effective therapy for patients with Waldenstrom’s macroglobulinemia,” said Steven P. Treon, MD, PhD, Director of the Bing Center for Waldenstrom’s Macroglobulinemia at the Dana-Farber Cancer Institute and Associate Professor at Harvard Medical School, and, who led the trial.

In addition to Breakthrough Therapy, the FDA granted Imbruvica priority review and orphan drug designation for treatment of WM. The agency’s approval comes more than two months ahead of its prescription drug user fee goal date.

“Waldenstrom’s macroglobulinemia patients and physicians have been waiting for a treatment specifically studied and approved to treat this rare disease,” said Carol Harrington, President of the International Waldenstrom’s Macroglobulinemia Foundation. “The approval of Imbruvica is an important milestone for the entire global WM community and has the potential to positively impact our patients, their physicians and caregivers.”

Source: US Food and Drug Administration; Janssen Biotech, Inc.

Roche receives FDA clearance for next generation cobas MRSA/SA Test

PLEASANTON, Calif. – Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the US Food and Drug Administration (FDA) has provided 510(k) clearance for the cobas® MRSA/SA Test for the early, simultaneous detection of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (SA) directly from nasal specimens. The cobas® MRSA/SA Test detects both organisms from a single specimen, providing accurate and reliable results for effective prevention and control of MRSA/SA infections.

“Numerous successful surveillance programs have led to a significant decrease in the rate of MRSA clinical infection in many organizations, and a dramatic reduction in postoperative surgical infections when screening for SA is done.  Importantly, the fight against healthcare-associated infections continues to advance, as evidenced by this new test that can rapidly detect both MRSA and SA in a single assay,” said Lance R. Peterson, MD, Director of Microbiology and Infectious Diseases Research at NorthShore University HealthSystem and Clinical Professor of Pathology and Medicine at the University of Chicago, Pritzker School of Medicine. “The cobas® MRSA/SA Test demonstrated excellent performance in detecting both MRSA and SA strains in samples collected throughout the US. Compared to culture testing, the cobas® MRSA/SA Test offers confidence in identifying colonized patients the first time they are evaluated, aiding in the prevention of MRSA disease and post-operative SA surgical infections.”

“Healthcare-associated infections continue to be a leading cause of mortality in US medical settings,” said Paul Brown, Head of Roche Molecular Diagnostics. “With the addition of the cobas® MRSA/SA Test to our expanding menu of tests for the cobas® 4800 System,  Roche offers laboratories and clinicians a highly efficient molecular solution to aid in the overall management and prevention of healthcare-associated infections, leading to lower costs for hospitals and optimal patient care.”

The cobas® MRSA/SA Test, a polymerase chain reaction (PCR)-based assay that runs on the automated cobas® 4800 System, offers labs the most simplified workflow available with a simple de-cap and loading of the primary sample vial onto the cobas® 4800 System. This approach requires less hands-on-time, enabling laboratory staff to spend time on other critical tasks. In addition, this streamlined workflow can help labs reduce costs and improve turnaround time.

About methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA)
Approximately one third of the population carries Staphylococcus aureus as normal flora in the anterior nares, which can lead to opportunistic infections. Staphylococcus aureus has evolved resistance mechanisms due to frequent exposure to antibiotics in health care settings. Recent reports show up to 85% of invasive MRSA infections identified as healthcare-associated, resulting in over 90,000 infections and 18,000 deaths in 2005 alone1. Surgical site infections, ventilator assisted pneumonia, and blood stream infections attributed to colonized central lines are the most frequent manifestations of disease. Active surveillance to identify carriers is helping to mitigate the potential consequences of disease, providing relief to patients and healthcare institutions facing the challenges of escalating costs.

About the cobas 4800 System

The cobas 4800 System offers true walk-away automation of nucleic acid purification, PCR  set-up and real-time PCR amplification and detection to help laboratories achieve maximum efficiency. The expanding system menu in the U.S. currently includes the cobas® CT/NG Test (chlamydia/gonorrhea), cobas HPV Test, cobas BRAF V600 Mutation Test and cobas EGFR Mutation Test.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, infectious diseases, inflammation, metabolism and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2012, Roche had over 82,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 45.5 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

1. Klevens et al. Invasive Methicillin-Resistant Staphylococcus aureus Infections in the United States. JAMA. 2007;298:63–1771

Source: Roche

FDA Approves New Glucose Monitoring App for Data-Sharing Among Diabetic Patients and Caregivers

The US Food and Drug Administration (FDA) allowed marketing of the first set of mobile medical apps that allow diabetics to automatically and securely share data from a continuous glucose monitor (CGM) with other people in real-time.

The Dexcom Share Direct Secondary Displays system’s data-sharing capability allows diabetes patient caregivers to monitor an individual’s blood sugar levels remotely. Other CGMs are also available on the market, however Dexcom Share is the first to receive the FDA’s approval.

The app allows caregivers and families to keep an eye on a diabetes patient’s glucose levels remotely, in order to avoid complications, such as hyperglycemia. The Dexcom Share involves two apps, one which would be downloaded by the patient, who will be able to set up “followers” that can view their information and the second would be downloaded by the caregiver to view the CGM data in real time. The patient can share data with up to five followers.

The system includes a small, wire-like sensor which a patient would insert just under the skin. The device continuously transmits data to a monitor that is worn externally. When used along with a blood glucose meter, CGM information can help diabetes patients detect when blood glucose values are approaching dangerously high and dangerously low levels.

“This innovative technology has been eagerly awaited by the diabetes community, especially caregivers of children with diabetes who want to monitor their glucose levels remotely,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health. “Today’s marketing permission paves the way for similar technologies to be marketed in the United States.”

Dexcom said that it anticipates to ship the Share receiver to new patients in March. This is the first Dexcom system that is mobile compatible without the use of a docking system.

The app was approved under the FDA’s de novo process, which was created for low- to moderate-risk devices, which doesn’t require the same review process as more complicated products. It is the first to receive regulatory approval for US sales since the FDA began regulating mobile medical apps as devices in 2013.

“The Dexcom Share receiver represents a significant step forward for our company and our mobile strategy, but more importantly, it will provide a huge improvement for people managing their diabetes and for those parents and caregivers who help them each and every day,” said Kevin Sayer, President and Chief Executive Officer of Dexcom. “The FDA understands the importance of this type of innovation and the need to regulate it appropriately, and we could not be more pleased with the speed at which they reviewed and approved this important innovation.”

Sources: US Food and Drug Administration; DexCom, Inc.; Specialty Pharma Journal

Protein-based Therapy Shows Promise against Resistant Leukemia

Binding of the protein (green) to the surface of leukemia cells results in cell death via destruction of the cell’s nucleus (dark red) into pieces

LOS ANGELES (January 26, 2015) – Resistance of leukemia cells to contemporary chemotherapy is one of the most formidable obstacles to treating acute lymphoblastic leukemia (ALL), the most common form of childhood cancer.  Now researchers at Children’s Hospital Los Angeles (CHLA) have designed and developed a new protein-based therapy they believe will prove highly effective against drug-resistant leukemia cells.  It may also amplify the potency of standard treatment options such as chemotherapy and radiation therapy.

They successfully accomplished this unique assembly of the two proteins in a single “fusion protein” and named this protein therapeutic candidate “CD19L-sTRAIL.”  In their study, Uckun and collaborators have demonstrated that their engineering converted sTRAIL into a much more potent “membrane-anchored” form that is capable of triggering apoptosis, even in the most aggressive and therapy-resistant form of human leukemia cells.Their work, published online January 26 by the Journal of Clinical Investigation, demonstrated the efficacy and safety of the new fusion protein in mouse models of aggressive human leukemia using leukemia cells taken directly from patients with ALL.

Occurring at an annual rate of 35 to 40 cases per million people in the U.S., ALL represents approximately 25 percent of cancer diagnoses among children under the age of 15. Historically, ALL had a high mortality rate; nearly 80 percent of children who developed the disease did not survive long term. Today, those numbers have been reversed, with almost 80 percent of children affected by ALL achieving long- term survival.

“That’s great news, unless your child is one of the 20 percent,” said the study’s principal investigator Fatih M. Uckun, MD, PhD, of the Children’s Center for Cancer and Blood Diseases at CHLA and the Norris Comprehensive Cancer Center of the University of Southern California (USC). “Despite advances in available therapies, unmet and urgent needs remain in the fight against leukemia.  We still have children with disease that our drugs can’t help enough. And for patients who relapse, their chances of long-term survival are less than 20 percent. We’ve got to do better.”

TNF-related apoptosis-inducing ligand (TRAIL) is a protein functioning as a ligand that induces apoptosis, or cell death. Produced by the immune system cells, it has the potential to cause apoptosis in tumor cells by binding to two so-called “death receptors”, also known as TRAIL-receptor 1 and TRAIL-receptor 2.

“TRAIL is a naturally occurring part of the body’s immune system that kills cancer cells without toxicity to normal cells.  However, earlier clinical trials using TRAIL as a potential anti-cancer medicine candidate have not been successful, largely because of its propensity to bind, not only to cancer cells, but also to ‘decoy’ receptors,” explained Uckun, who is also a professor of pediatrics at Keck School of Medicine of USC.

Uckun and collaborators discovered a previously unknown protein – CD19-Ligand – a natural ligand of human CD19, which is expressed by almost all ALL cells.  They hypothesized that fusing it by genetic bioengineering to the portion of TRAIL (known as sTRAIL) that can kill cancer cells, would produce a powerful weapon against leukemia cells.  Unlike chemotherapy drugs, this precision medicine candidate would seek out, bind and destroy only leukemia cells carrying CD19 as the target docking site.
“Due to its ability to anchor to the surface of cancer cells via CD19, CD19L-sTRAIL was 100,000-fold more potent than sTRAIL, and consistently killed more than  99 percent of aggressive leukemia cells taken directly from children with ALL –  not only in the test tube, but also in mice,” said Uckun. Administering only two or three doses of CD19L-sTRAIL significantly improved the survival outcome of mice challenged with an otherwise invariably fatal dose of human leukemia cells, without side effects.  Its therapeutic potency in mice was superior to that of standard chemotherapy combinations as well as radiation therapy.

“The biggest challenge is to cure patients who experience a recurrence of their cancer, despite intensive chemotherapy,” Uckun concluded. “We are hopeful that the knowledge gained from this study will open a new range of effective treatment opportunities for children with recurrent leukemia.”

Additional contributors include Dorothea E. Myers, Zahide Ozer, Osmond J. D’Cruz and Hong Ma of the Children’s Center for Cancer and Blood Diseases and Children’s Hospital Los Angeles; Sanjive Qazi of CHLA and Gustavus Adolphus College, St. Paul, MN; and Rebecca Rose of Rose Pathology Services, St. Paul. The project was supported by a 2011 V-Foundation Translational Research Award and in part by DHHS grants R21-CA-164098, U01-CA-151837 and R01-CA-154471 from the National Cancer Institute, part of the National Institutes of Health.

About Children’s Hospital Los Angeles
Children’s Hospital Los Angeles has been named the best children’s hospital on the West Coast and among the top five in the nation for clinical excellence with its selection to the prestigious U.S. News & World Report Honor Roll. Children’s Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States. Children’s Hospital is also one of America’s premier teaching hospitals through its affiliation since 1932 with the Keck School of Medicine of the University of Southern California.

Source: All Children’s Hospital Los Angeles