Building a biologics boom

Fifth-generation anticancer biologics poised to enter $120-billion market

Lloyd Dunlap
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BOSTON—Advances in formulation and delivery will helppharmaceutical firms modify proven drugs by targeting molecules now off patent,besides developing fifth-generation drugs designed to activate stem cells tofight diseases such as cancer.
Fourth-generation biologics, with improved delivery andpharmacokinetics, will continue to drive the overall biologics industry, whichis already worth more than $120 billion, according to a recent Lux Research report,"Of Biologics and Cells: Are Formulation and Delivery Technologies Keeping Upwith the Progression?"
"With advances in cloning and assay development, thetherapeutics industry has managed to artificially engineer these molecules toaddress therapeutically important targets," says Yan Xiang Yang, a Lux Researchanalyst and the lead author of the report. "Fifth-generation biologics deliverywill focus on manipulating molecular switches that turn on specific cellulardifferentiation and metabolic pathways. Initial switch regulators will bemonoclonal antibodies designed to up-regulate, as opposed to down-regulate,pathways and cellular interactions. To that extent, the ability to maskimmunogenicity and extend circulating half-life, either through direct proteinengineering or via encapsulation or coating, will be important for chronic,on-demand administration."
Looking longer term, the movement towards patientconvenience and at-home healthcare delivery via self-injectable devices willnecessitate improvements in cold-chain processing, protein stabilization,emulsion and penetrants, as well as encapsulation and coatings. As more physiobiologicalinformation is gained about targets, it may be possible to engineer shorterproteins for greater bioactivity and loading, Yan states.
"The possibility also exists for positive up-regulation ofcellular activity by fifth-generation biomolecular drugs that may be used toactivate stem cells or boost immune system functions for diseases such ascancer," Yan adds.
Underscoring both Yan's analysis and the buzz about cancerimmunotherapy heard at this summer's American Society of Clinical Oncologyconference, Immunovaccine Inc., a clinical-stage vaccine company, is advancingits ovarian cancer vaccine into Phase II clinical trials with its newcollaborator, NCIC Clinical Trials Group, a Canadian academic clinical trialscooperative. The study will enroll approximately 250 patients in order toevaluate response to Immunovaccine's DPS-Survivac in combination with low-doseoral cyclophosphamide. In a second Phase II study based in Rome, DPX-Survivacwill be tested in newly diagnosed glioblastoma patients.
And in a third recently announced development, a projectsupported by an $8-million European Union Framework 7 program grant will aim atdeveloping a novel class of therapeutic cancer vaccines. The Glioma ActivelyPersonalized VAccine Consortium (GAPVAC) is the first EU-funded initiativeaimed at clinically developing biomarker-guided actively personalized vaccines(APVACs) to treat cancer. The consortium consists of 14 organizations from thebiotech industry and academia led by immatics biotechnologies GmbH(coordinator) and BioNTech AG (vice coordinator). Both companies are located inGermany and are dedicated to a biomarker-guided approach to fight cancer. APhase I clinical trial that will enroll 30 newly diagnosed glioblastomapatients is expected to start in 2014.
Putting numbers to the current market, Lux Research reportsthat autoimmune and inflammatory biologics lead, followed by hematologicdisorders, metabolic disorders (which is dominated by insulin analogs) andcancer, which together account for more than $100 billion in sales. The mostlucrative indication is autoimmune diseases; the top-four drugs sharing morethan $25 billion in sales and the next seven adding another $14 billion. Thehematologic disorders market, worth $21.5 billion, is slightly larger than the$20.5-billion cancer drug market.
Roche/Genentech, Novo Nordisk, Amgen and Sanofi/ Genzyme areclear leaders in this game, Yan states, with Abbvie holding onto blockbusterHumira. The top-10 best-selling biologics in 2012 were Humira, Enbrel, Rituxan,Lantus, Herceptin, Avastin, Remicade, Neulasta/ Neupogen, Copaxone and Lucentis.
Several factors place antibodies at the forefront of thebiologicals wave, including the depth and breadth of knowledge supporting theiruse, as well as innate properties such as stability and targeting ability.Blockbuster successes such as Herceptin and Lucentis have also driven others inthe industry to follow suit with a likely glut of such therapies on thehorizon.
Challenges remain for other biologics. Physical instability,chemical degradability, enzymatic digestibility and the inability to penetratebarriers are some key hurdles facing developers of nucleic acid technologies. Also,with only one active cellular therapy trial in the United States, progress incell-based therapeutics will remain slow, leaving protein therapeutics thedominant biologic therapy.
"Based on what we are observing, there is exciting ongoingwork enabling the delivery of these biologics via more convenient routes, suchas subcutaneous delivery or even oral," Yan notes. "Achieving this would be abreakthrough in the biologics sector, enhancing patient compliance and ease ofuse. Some ongoing examples include subcutaneous delivery of Herceptin in a Halozyme/Rochelinkup, and the long-awaited progress in oral insulin."

Lloyd Dunlap

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