FDA Approves First Biosimilar Drug, New Indication for Lenalidomide, and more

FDA Approves First Biosimilar Drug
Zarxio (filgrastim-sndz), a biosimilar product of filgrastim, was recently approved by the U.S. Food and Drug Administration (FDA). This is the first biosimilar drug – a biological product that is approved based on demonstrations that it is highly similar to an already-approved biological product, known as the reference product – to receive approval. Filgrastim-sndz is approved for all of the indications of the reference product, which was initially licensed in 1991. The FDA’s approval of filgrastim-sndz is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data, and other clinical safety and effectiveness data that demonstrate its similarity to the reference product. “Biosimilars will provide access to important therapies for patients who need them,” said FDA Commissioner Margaret A. Hamburg, MD. “Patients and the health-care community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy, and quality standards.”

Source: FDA News Release


FDA Expands Indications for Lenalidomide
Lenalidomide plus dexamethasone is now approved for the treatment of patients with newly diagnosed multiple myeloma. The U.S. FDA had previously approved this combination in June 2006 for the treatment of patients with multiple myeloma (MM) who had received at least one prior therapy. The recent decision to expand the treatment’s indication was based on results from multiple phase 3 studies, including the randomized, open-label, three-arm FIRST trial (MM-020/IFM 07-01). In this study, continuous lenalidomide + dexamethasone (Rd Continuous) until disease progression was compared with melphalan, prednisone, and thalidomide (MPT) administered for 18 months. Researchers also evaluated a fixed duration of 18 cycles of lenalidomide + dexamethasone in 1,623 newly diagnosed patients who were not eligible for stem cell transplant. The primary endpoint was median progression-free survival. Compared with MPT, the Rd Continuous combination resulted in significantly longer PFS (25.5 months vs. 21.2 months; HR = 0.72; p = 0.0001), median overall survival (58.9 months vs. 48.5 months; HR = 0.75; 95% CI 0.62–0.9), and a 25 percent reduction in the risk of death. The most common adverse events reported in both groups included diarrhea, anemia, neutropenia, fatigue, and back pain.

Source: FDA News Release


Panobinostat Approved for the Treatment of Relapsed MM
The U.S. FDA recently approved panobinostat for the treatment of patients with MM, making it the first histone deacetylase (HDAC) inhibitor approved for this condition. The drug works by inhibiting the activity of HDAC enzymes, which may slow the production of plasma cells in multiple myeloma patients or cause these cells to die. Panobinostat is intended for patients who have received at least two prior standard therapies – including bortezomib and an immunomodulatory agent – and is to be used in combination with bortezomib and dexamethasone. The safety and efficacy of the drug (in combination with bortezomib and dexamethasone; PBD) was demonstrated in a clinical trial of 193 patients with MM who were randomly assigned to receive PBD or bortezomib + dexamethasone (BD) alone. Patients in the PBD group had longer PFS (10.6 months vs. 5.8 months in the BD group; HR = 0.52; 95% CI 0.36-0.76). In addition, 59 percent of PBD-treated participants saw their cancer shrink or disappear after treatment, compared with only 41 percent in the BD group. The most common side effects of the drug were diarrhea, tiredness, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting and weakness. Panobinostat does carry a Boxed Warning about severe diarrhea and severe and fatal cardiac events, arrhythmias, and electrocardiogram changes that have occurred in patients receiving the medication.

Source: FDA News Release


Scientists Map the Human Epigenome
Using massive data analysis to understand how and why certain genes turn on and off in human cells, researchers have released the first comprehensive map of the human epigenome. Much as mapping the human genome laid the foundations for understanding the genetic basis of human health, researchers hope that this new epigenomic roadmap will further unravel the complex links between DNA and disease. The findings were recently published in Nature.

Almost all human cells have identical genomes that contain instructions on how to make the many different cells and tissues in the body. With support from the National Institutes of Health Common Fund’s Roadmap Epigenomics Program, scientists compared the epigenomic signatures across 111 types of cells and tissues, providing new insight into which parts of the genome are used to make a particular type of cell.

The resulting information can help scientists understand how changes to the genome and epigenome can lead to conditions such as Alzheimer’s disease, cancer, asthma, and fetal growth abnormalities.

“What the Roadmap Epigenomics Program has delivered is a way to look at the human genome in its living, breathing nature from cell type to cell type,” said Manolis Kellis, PhD, professor of computer science at the Massachusetts Institute of Technology, and senior author of the paper.
Researchers can now take data from different cell types and directly compare them. “These 111 reference epigenome maps are essentially a vocabulary book that helps us decipher each DNA segment in distinct cell and tissue types,” explained Bing Ren, PhD, co-author of the Nature paper. “These maps are like snapshots of the human genome in action.”

Sources: NIH news release; Roadmap Epigenomics Consortium. Integrative analysis of 111 reference human epigenomes. Nature. 2015;518:317-30.


Engineering Platelets on Demand?
A team led by researchers at Tufts University School of Engineering and the University of Pavia has developed a three-dimensional tissue system that can generate functional human platelets. This first-of-a-kind system successfully reproduces the complex structure and physiology of human bone marrow using a biomaterial matrix of porous silk. The new system is capable of producing platelets for future clinical use and also provides a laboratory tissue system to advance study of blood platelet diseases, according to the researchers’ report, recently published in Blood.

“New insight into the formation of platelets would have a major impact on patients and health care. In this tissue system, we can culture patient-derived megakaryocytes – the bone marrow cells that make platelets – and also endothelial cells, which are found in bone marrow and promote platelet production, to design patient-specific drug administration regimes,” said Alessandra Balduini, MD, a co-corresponding author on the paper.
The bioreactor combines microtubes spun of silk, collagen, and fibronectin surrounded by a porous silk sponge. Megakaryocytes – some of which were derived from patients – were seeded into the engineered microvasculature.

Laboratory tests showed that the platelets generated and recovered from the tissue system were able to aggregate and clot. While the number of platelets produced per megakaryocyte was lower than that normally made in the body, the researchers were able to increase platelet production by embedding the silk with active endothelial cells and endothelial-related molecular proteins that support platelet formation.

The new system can also provide an in vitro laboratory tissue system with which to study mechanisms of blood disease and to predict efficacy of new drugs — providing a more precise and less costly alternative to in vivo animal models. The researchers also hope that the platelets produced can be used as a source of growth factors for wound healing in regenerative medicine, including healing of ulcers and burns, and stimulation of bone tissue regeneration in dentistry and maxillofacial plastic surgery.

Source: Di Buduo CA, Wray LS, Tozzi L, et al. Programmable 3D silk bone marrow niche for platelet generation ex vivo and modeling of megakaryopoeisis pathologies. Blood. 2015 January 9. [Epub ahead of print]

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