News Summaries-September 2010
Additional news items are summarized in the News Module and News Archives (Requires Login).
The FDA issued a Refuse to File letter for accelerated approval for the Biologics License Application (BLA) of Genentech's anticancer agent trastuzumab-DM1 (T-DM1), an antibody-drug conjugate (ADC) in development for HEr2-positive breast cancer. Genentech will continue with EMILIA, the ongoing phase III registrational trial (protocol ID: TDM4370g; 2008-005 713-22; NCT00829166) with T-DM1, work with the FDA, and submit a new T-DM1 BLA in mid-2012.
After meeting with regulatory agencies in the USA and Europe, Bavarian Nordic is planning to initiate a registrational phase III clinical trial in 2011 to evaluate Prostvac in 1,200 patients with asymptomatic or mildly symptomatic hormone-refractory prostate cancer (HRPC). The FDA has granted Prostvac fast track designation and the company plans to file for a special protocol assessment (SPA) later in 2010.
According to topline results, the phase III clinical trial (protocol ID: A6181087; SUN1087; NCT00457392) with Pfizer's anticancer drug sunitinib (Sutent) in combination with erlotinib versus erlotinib monotherapy in patients with previously treated advanced non-small cell lung cancer (nsclc), failed to meet its endpoint of overall survival (OS) although a statistically significant improvement was noted in progression-free survival (PFS), a secondary endpoint. No new or unexpected types of adverse events were observed in the trial. A presentation of the results of this trial has been submitted to the European Society for Medical Oncology (ESMO) Congress, October 8-12, 2010 in Milan, Italy.
According to top-line results, SPECTRUM, a phase III clinical trial (protocol ID: 20050251; 20050251; NCT00460265) to compare Amgen's anticancer agent Vectibix (panitumumab) as a first line treatment in 658 patients with recurrent and/or metastatic squamous cell head and neck cancer randomized to a standard cisplatin plus 5-FU regimen, with or without Vectibix (9 mg/kg), failed to meet its primary endpoint of overall survival (OS). The addition of Vectibix to platinum-based chemotherapy did not result in a statistically significant improvement in OS compared to chemotherapy alone; median OS was 11.1 months with Vectibix compared to 9.0 months with chemotherapy alone for a hazard ratio (HR) of 0.87.
Investigators at Hokkaido University Graduate School of Medicine (Sapporo, Japan) developed a fluorescence resonance energy transfer (FRET)-based biosensor for the measurement of Bcr-Abl activity and its response to drugs such as imatinib in living cells that represents a quick and practical method for the prediction of both current and future therapeutic responses in patients with chronic myelogenous leukemia (CML). This novel method may also be used to develop biomarkers for early cancer detection, cancer prognosis, and to identify drug targets (Pubmed link).
In vitro Assessments/Novel Targets
BRCA2
Scientists purified the protein expressed by the BRCA2 gene paving the way for the creation of antibodies to BRCA2 to be used as improved diagnostics and for the development of therapeutics that activate or inhibit the interaction between BRCA2, RAD51 and DNA. (login for more)
Polycomb group ring finger 4 (PCGF4), Bmi-1
Bmi-1, a member of the polycomb family of transcription factors, has been implicated in the maintenance of self-renewal of cancer stem cells. Bmi-1 is overexpressed in various epithelial tumors, including lung, breast, prostate, colorectal, liver, and CNS cancer, as well as in hematologic malignancies, and plays a role in drug resistance and treatment failure. Elevated levels of Bmi-1 in cancer cells correlate with advanced tumor grade and a poor prognosis. Because Bmi-1 is a factor necessary for tumor stem cell survival, reduction of this protein is likely to increase susceptibility of tumors to prevailing chemotherapy and radiotherapy treatments. Currently, inhibitors of Bmi-1 are in early development and it is also being considered as a target for immunotherapy.
B-cell CLL/lymphoma 6 (BCL6)
B-cell CLL/lymphoma 6 (BCL6) is a zinc finger transcription factor critical for the development of a diverse primary B-cell repertoire. BCL6, the most commonly involved oncogene in diffuse large B-cell lymphoma (DLBCL), is frequently translocated and hypermutated in DLBCL, and may be involved in the pathogenesis of this disease. Investigators at Weill Cornell Medical College, the University of Maryland, and the University of Toronto, funded by a grant from the Samuel Waxman Cancer Research Foundation, used an integrated biochemical and computational approach to design a small molecule inhibitor of BCL6 as a novel treatment for DLBCL (article).
Neuropilin (NRP1)
Neuropilin 1 (NRP1) is a membrane-bound (transmembrane) glycoprotein, a co-receptor to a tyrosine kinase receptor for both vascular endothelial growth factor (VEGF) and semaphorin family members, primarily SEMA3A. NRP1 plays versatile roles in angiogenesis, axon guidance, cell survival, migration, and invasion. NPR1 is overexpressed in various malignancies including breast, ovarian, colorectal, brain, and pancreatic cancer and osteosarcoma and leukemia, among others. NRP1 inhibition appears to sensitize tumors to vascular endothelial growth factor (VEGF) blockade, enhancing the latter's antiangiogenesis effects. Antagonists of NRP1 are in preclinical and clinical stage of development.
CD200, a negative regulator of the immune system
Normally expected innate immune responses against malignant cells are prevented by negative regulation of the immune system by the tumor itself. CD200 has been identified among effectors used by tumors to suppress T-cell-mediated immune responses in both hematologic malignancies and solid tumors. Therefore, inhibition of CD200 appears to be a potential therapeutic strategy for a variety of malignancies and is currently being evaluated in clinical trials.
In vitro tests (IVT) in ovarian cancer
Over 30 companies are developing in vitro tests in ovarian cancer for early diagnosis and further assessment of disease status, to select patients and/or assess tumor sensitivity for certain treatments, for treatment/disease monitoring, etc. In addition, many trials evaluating novel targeted agents in clinical development in ovarian cancer are using some type of biomarker to select patients, assess drug effectiveness, and interpret results.
Additional items are summarized in the In Vitro Assessments/Novel Targets page.
Special Report
Inhibition of ALK for the Treatment of Cancer
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) found at high levels in cancer cells, where it is believed to play an important role in tumor cell growth and survival. Genetic activation of ALK can result from gene amplification, kinase-domain point mutations, or by fusion of the kinase domain to structural genes. A number of chromosomal rearrangements leading to enhanced ALK activity have been described to date that are implicated in a number of different malignancies, including anaplastic large cell lymphoma (ALCL), breast, ovarian and non-small cell lung cancer, and hereditary and sporadic neuroblastoma. Despite the rarity of ALK-related malignancies, thousands of patients would be candidates for such a treatment annually worldwide. Therefore, ALK inhibitors targeting certain ALK translocations in cancer cells may duplicate the success of imatinib (Gleevec) by addressing a highly specific target found in a small percent of malignancies that nevertheless represent significant populations worldwide.
ALK recently came to prominence as a result of a positive outcome of a phase II clinical trial with crizotinib, a specific ALK inhibitor, in patients with non-small cell lung cancer (nsclc) with the ELM4-ALK rearrangement. Because ALK is generally not expressed in normal adult tissues, it represents a highly promising molecular target for cancer therapy. A number of small molecule Alk inhibitors are also in development that are addressing ALK mutations that confer resistance to first generation drugs like crizotinib and future developments may include immunotherapies and gene silencing approaches. In addition in vitro tests are in development to detect ALK and its manifestations in patients with various malignancies suspected of harboring ALK. (login for more. . .)
NICE Final Appraisal Determinations (FAD)
UK's National Institute of Health and Clinical Excellence (NICE) has approved 2 anticancer drugs for reimbursement and rejected 2 others. Denial of many well accepted anticancer treatments in the rest of the developed world to England's patients has prompted politicians and doctors to lobby the coalition government to introduce a proposed £200 million program to fund life-prolonging anticancer drugs not covered by NICE. (login for more. . .)
The I-SPY 2 Trial and Other Novel Clinical Trial Approaches
In a unique collaboration, the National Cancer Institute (NCI) and the FDA, led by the the Foundation for the National Institute of Health, have initiated the I-SPY 2 (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2) phase II clinical trial in patients with breast cancer to speed up the development of promising treatments (trial link).
All in all, the trial will test up to 12 investigational drugs belonging to different therapeutic classes in combination with a standard chemotherapy regimen of paclitaxel, doxorubicin, and cyclophosphamide. Results will be shared by all the participants, and will be broadly available to the entire cancer R&D community. The trial will combine clinical and biomarker data on a comprehensive scale and it is hoped it will aid in the design of advanced, smaller, and less expensive phase III trials that test the right drug in the right patients. Patients are selected using MammaPrint to score the tumor and TargePrint to identify HEr2-positive disease. The first phase is testing three drugs, veliparib (ABT-888), a PARP inhibitor under development by Abbott, and 2 Pfizer drugs, figitumumab (CP-751871), an IGF1r inhibitor and neratinib (HKI-272), a pan-ErbB inhibitor. Among the remaining novel agents to be evaluated are two Amgen drugs, AMG 655 (conatumumab), an APO/TRAIL inhibitor, and AMG 386, an angiogenesis inhibitor. These drugs will be tested in the neoadjuvant setting in women with locally advanced high risk, fast growing tumors (~2.5 cm), to see if the combination administered over 12 weeks can reduce the size of the tumor before surgery. This indication accounts for about 10% to 15% of all cases of breast cancer and leads to a higher mortality than smaller, mammography-detected malignancies. Because the drugs are administered in the neoadjuvant setting, their effect will be immediately known when the tumor is removed during surgery. Investigators will observe the treatment's effectiveness on the tumor itself instead of waiting to see how the patient fares over a period of time, sometimes several years. The trial is to enroll about 800 patients. Principal investigators (PI) of the trial are Laura Esserman MD, at the University of California San Francisco, and Donald Berry, PhD, at the University of Texas M. D. Anderson Center.
In another innovation in clinical trial design, Pier Paolo Pandolfi, MD, at Beth Israel Deaconess Medical Center (Boston, MA) is concurrently evaluating a drug in patients in a clinical trial and in animal models (mouse) of the same disease. The project, funded with a $4.2 million economic stimulus grant from the National Cancer Institute (NCI), is attempting to integrate bedside/bench results to streamline and accelerate the development of anticancer agents. In addition to the stimulus grant, Dr. Pandolfi also received a 5-year, $3.75 million grant to create a blueprint for how to best employ this clinical trial approach. In the pilot project, mice carrying gene mutations associated with human prostate or lung cancer are treated with the same drug(s) administered to patients. Coordinating treatment results between patients and animals should reveal the molecular profile most effectively addressed by the drug being tested. Also, emergence of resistance in mice may lead to the discovery of more effective combinations in humans (news link).
Yet another clinical trial (protocol ID: SO-BCA-001; NCT01074814), based on technology developed by George Mason University researchers, is customizing treatment in patients with metastatic breast cancer by choosing approved drugs based on their mechanism of action as it relates to the pathways activated in each patient's tumors.
Braf, BrafV600E and related pathway inhibitors
The complexities of targeted anticancer treatment were once again brought to the forefront as researchers report that in patients with malignant melanoma harboring wild type Braf, treatment with Braf inhibitors may spur tumor growth (news link). Although Braf inhibitors have resulted in dramatic responses in some patients in early stage clinical trials, two research groups found that in laboratory tests the drugs spurred the growth of some tumors. Current inhibitors primarily target the V600E Braf mutation that activates the mitogen-activated protein kinase (MAPK) signaling pathway. This mutation is present in about 50% of cases of malignant melanoma and at lower rates in many other malignancies. In preclinical trials, the BrafV600E inhibitors appeared to activate signaling in melanoma tumors with wild type (wt) Braf and mutations in the Ras gene, which is part of the Braf pathway. Also there may be another player, Craf (RAF1) that activates the ERK1/2 pathway in wt Braf cells that are resistant to Braf(V600E) inhibitors (Halaban R, etal, Pigment Cell Melanoma Res, 10 Feb 2010; epub ahead of print). These findings imply that direct inhibition of one or more targets may be insufficient or even harmful depending on the complete molecular profile of the cancer cell harboring the intended target. For instance, the behavior of the inhibitor of a specific target may vary depending on other mutations/activated pathways in a given cancer cell. Such a scenario renders highly targeted approaches impractical favoring more generalized anticancer treatments that target processes shared by most cancer cells as in the case with cytotoxics, angiogenesis, etc. For instance, the HSP90 inhibitor geldanamycin effectively promotes the degradation of Craf to overcome resistance to RAF inhibition in a subset of BRAF-mutant tumors. Currently, the Braf findings could have implications for the multi-targeted anticancer agent sorafenib (Nexavar; Bayer), the only approved documented Braf inhibitor, and for the various novel Braf inhibitors in clinical and preclinical development, as well as drugs inhibiting the Ras/Raf/MEK/ERK pathway that is activated in approximately 30% of all human tumors.
Cancer Clinical Pipeline Updates
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The Clavis Pharma Pipeline
Clavis Pharma is evaluating in clinical trials two novel versions of approved cytotoxic agents with unique attributes and delivery approaches that promise to increase effectiveness and overcome resistance.
The Transgene Clinical Pipeline
The Transgene clinical pipeline in oncology focuses on therapeutic vaccines and immunotherapeutics for the management of various malignancies including non-small cell lung cancer (nsclc), primary and hepatocellular carsinoma (HCC), and cervical intraepithelial neoplasia (CIN) and cervical cancer, among others. The company is also developing oncolytics currently in the preclinical stage. Transgene is seeking a partner to develop TG3003, a humanized monoclonal antibody (MAb) targeting colony-stimulating factor 1 receptor (CSF1r), or CD115, expressed in a variety of tumors. Transgene also participates in the ADNA program seeking to discover and validate prognostic and predictive biomarkers associated with cancer and infectious and genetic diseases. (ADNA link)
The Facet Biotech Pipeline
In acquiring Facet Biotech, Abbott is gaining promising biologic agents in immunology and oncology, including daclizumab in phase II clinical trials in multiple sclerosis (MS) that is expected to enter phase III development in the second quarter of 2010, oncology compounds in early to mid-stage development, and a technology platform that is used to optimize monoclonal antibodies (MAb) for therapeutic indications.
The OSI Pharmaceuticals Pipeline
OSI Pharmaceuticals is evaluating 3 agents in clinical trials, all oral targeted drugs with one in phase III clinical trials.
The AVEO Pharmaceuticals Pipeline
Aveo Pharmaceuticals is evaluating 2 anticancer agents in clinical trials, including a phase III clinical trial with tivozamib, its lead antiangiogenesis inhibitor, in patients with refractory advanced or metastatic renal cell carcinoma (RCC).
The CytRx Pipeline in Oncology
As of January 2010, CytRx had 2 new and 1 marketed anticancer drug in clinical development and was planning multiple phase II clinical trials in both solid tumors and hematologic malignancies.
The Clavis Pharma Pipeline
Clavis Pharma is developing three distinct anticancer agents, two in clincial trials and one in preclinical evaluation. A recent partnering agreement with Clovis Oncology is accelerating development of its CP-4126, a lipid formulation of gemitabine for the treatment of pancreatic cancer. The mechanism of action of CP-4126 may overcome cancer cell resistance that commonly develops with gemcitabine. A test is in development to classify patients according to the expression of the hENT1 (human equilibrative nucleoside transporter 1) pancreatic tumor protein, a cell membrane transporter believed to be critical for gemcitabine entry into tumor cells; CP-4126 enters and kills tumor cells in a hENT1-independent manner.
The AstraZeneca Oncology Pipeline
AstraZeneca has a well balanced clinical pipeline in oncology with 15 novel agents in clinical development, mostly targeted small molecule and biologic inhibitors. Targets include aurora B (STK12/Aurora-1); CD22; checkpoint 1 (Chk1); endothelin receptor type A (EDNRA), ETAr; ephrin type A receptor 2 (EphA2); epidermal growth factor receptor (EGFr ); HEr2/neu; HEr3; insulin-like growth factor 1 (IGF1); insulin-like growth factor 2 (IGF2); mammalian target of rapamycin (mTOR); mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinases (MEK); platelet-derived growth factor receptor alpha (PDGFrA); poly (ADP-ribose) polymerase (PARP); Src (c-src, ASV); Abl; vascular endothelial growth factor receptor (VEGFr) and VEGFr2; RET; glial cell-line derived neurotrophic factor receptor (GDNFr); and c-Kit. The pipeline consists of agents in all stages of development with one, Zactima (vandetanib), having been filed with the FDA and the EMEA, but sinsce withdrawn, for use in combination with chemotherapy for the treatment of advanced non-small cell lung cancer (nsclc) in patients previously treated with one anticancer therapy (second line); AstraZeneca will await results from ongoing trials to decide refiling for approval. The pipeline includes 3 agents having advanced to phase III development; 8 of the 15 agents are in early phase I development.
The NeoPharm Pipeline
Additional items are summarized in the Cancer Pipeline Updates (Requires Login).
Novel Anticancer Agents
The enrollment target of 500 patients was reached in TIVO-1, the global, randomized, controlled phase III clinical trial evaluating Aveo Pharmaceuticals' anticancer agent tivozanib compared to sorafenib (Nexavar; Onyx Pharmaceuticals) in patients with clear cell renal cell carcinoma (RCC).
Based on positive results from the phase IIb clinical trial (protocol ID: PX-171-003; PX-171-003-A1; NCT00511238) of single agent carfilzomib in patients with relapsed or refractory multiple myeloma, Onyx Pharmaceuticals plans to submit an NDA to the FDA for accelerated approval of carfilzomib for this indication. A phase III clinical trial has been initiated in this indication and a second phase III clinical trial is to be initiated later in 2010.
A team at the University of Western Australia, in collaboration with Novasel, investigated in mice with non-melanoma skin cancer the effects of tea tree oil (news link), a natural substance from Melaleuca alternifolia, a tree native to New South Wales. Tea tree oil shrunk skin cancer in mice in just one day and eliminated them within three days (article). Further experiments indicated that the anticancer effect of the tea tree oil formulation may involve activation of the immune system. The team is looking for funding to conduct a clinical trial in about 50 individuals with precancerous lesions to test the agent's ability to prevent the development of skin cancer.
Crizotinib (PF-2341066, PF-1066), under development by Pfizer, is an orally bioavailable, ATP-competitive, small molecule inhibitor of hepatocyte growth factor receptor (HGFr)/c-Met and anaplastic lymphoma kinase (ALK) with cytoreductive antitumor properties in vivo. The drug is currently in several clinical trials in solid tumors and lymphoma with a phase III clinical trial being conducted in patients with non-small cell lung cancer harboring the ELM4-ALK translocation.
Neratinib, a novel HEr2 and EGFr inhibitor under development by Pfizer, appears to be a promising treatment for refractory HEr2-positive breast cancer, as indicated by results of phase I/II clinical trials presented at the 2010 IMPAKT Breast Cancer Conference. In a phase I/II clinical trial in combination with paclitaxel the overall response rate (ORR) was 69% (CR=5% and PR=64%). The ORR was better in women with hormone receptor positive tumors (84% versus 50%; p<0.05). Based on these results, a phase III trial is planned for the combination of neratinib and paclitaxel in the first line setting. In a phase I/II clinical trial with neratinib in combination with vinorelbine, among the 18 patients evaluable for efficacy, the ORR was 43% in lapatinib-naïve patients and 25% in those exposed to lapatinib. Tumor reductions were seen in 15/18 patients. In both trials, diarrhea was the most common toxicity that could be severe in some cases. Neratinib is also one of the drugs to be investigated in the I-SPY clinical program.
Ridaforolimus (MK-8669), under evaluation by Merck and Ariad Pharmaceuticals, blocks cancer cell growth and proliferation by inhibiting the mammalian target of rapamycin (mTOR). A phase III clinical trial with oral ridaforolimus was recently completed in patients with metastatic soft-tissue and bone sarcoma that responded favorably to chemotherapy. Ridaforolimus in various phase I and II clinical trials as monotherapy in non-small lung cancer expressing mutant Kras, and endometrial cancer and in combination with other targeted therapeutics, including trastuzumab in breast cancer and MK-0646 in solid tumors. Merck has undertaken a biomarker research program to design rational combinations with deforolimus, identify responder profiles, and inform decisions in alignment with the clinical trial program.
Figitumumab (CP-751871), under development by Pfizer, is a fully human IgG2 antibody with high affinity for human insulin-like growth factor (IGF) 1 receptor (IGF1r). There are over 16 agents in clinical development targeting IGF/IGF1r. Clinical evaluation of figitumumab was initiated in mid-2005, and the drug quickly moved to late stage development entering phase III clinical trials in non-small cell lung cancer in March 2008. ADVIGO (ADVancing IGF-IR in Oncology), an ambitious program was established at that time to evaluate fugitumumab, in combination with various standard chemotherapy regimens, in several major cancer types. However, in the past 5 years the clinical development of fugitumumab was dealt numerous setbacks and, currently, the drug is being evaluated only in phase I clinical trials in combination with standard chemotherapy in breast cancer and various solid tumors including Ewing's sarcoma and is slated to enter phase II clinical trials in extensive-stage small cell lung cancer (sclc). Fugitumumab is also one of the 3 novel agents to be originally evaluated in the I-SPY 2 clinical trial, an innovative adaptive trial that will determine which new drug agents are most effective with which types of breast cancer tumors and identify early indicators of response predictive of treatment success.
The new year has not been kind so far to developers of novel cytotoxics. Three new drugs, 2 about to be reviewed by ODAC, and one with recent results from late stage clinical trials seem to have to overcome significant hurdles in their quest for regulatory approval. Cell Therapeutics' pixantrone (Pixvuri) and ChemGenex Pharmaceutical's omacetaxine (Omapro) are to be reviewed by ODAC in the near future and Poniard Pharmaceuticals is planning FDA meetings to establish a regulatory path for its platinum drug picoplatin as a neuropathy-sparing platinum agent in metastatic colorectal cancer. More (Log in to continue)
In a report published in the journal Natural Products, investigators at Uppsala University, in Sweden, report that cardiac glycosides, among them oleandrin, proscillaridin A, digitoxin and digoxin, exhibit cytotoxic activity against colon cancer in combination with any of four clinically relevant cytotoxic drugs, 5-fluorouracil, oxaliplatin, cisplatin, or irinotecan.
Aflibercept (VEGF Trap), under development by Regeneron Pharmaceuticals and sanofi-aventis, is an inhibitor of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in late stage development in various malignancies. As of November 2009, three phase III clinical trials, in lung, colorectal and prostate cancer were >80% enrolled with results anticipated by mid-2010 and early 2011. Regeneron and sanofi-aventis also expanded and extended their existing global collaboration to discover, develop, and commercialize fully human therapeutic monoclonal antibodies (MAb) with the annual funding commitment by sanofi-aventis to increase from $100 million to $160 million beginning in 2010, and the research funding to extend through 2017.
Supportive Care
Denosumab (Prolia), under development by Amgen, is the first fully human monoclonal antibody (MAb) in late stage clinical development that specifically targets RANK Ligand (RANKL), an essential regulator of osteoclasts, the cells that break down bone. Among other indications, Prolia is being investigated for the treatment and prevention of bone loss resulting from hormone ablation in patients with breast and prostate cancer, as well as for its potential to delay bone metastases and inhibit and treat bone destruction in patients with multiple myeloma and across many stages of cancer. In direct evaluation against zoledronic acid (Zometa; Novartis), the current standard of treatment of bone loss associated with cancer metastasized to the bone, denosumab was superior to Zometa in preventing skeletal related events (SRE) and delayed worsening of bone pain in a phase III clinical trial of 2,046 patients with advanced breast cancer. In addition, denosumab also presented some potential tolerability advantages for many patients, including a lower incidence of renal toxicity and acute phase reactions, combined with the convenience of a monthly SC injection. Similarly, in another phase III clinical trial, denosumab was non-inferior to Zometa in the treatment of bone metastases in 1,776 patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma and superior to Zometa in delaying the time to the first on-trial skeletal related event (SRE) for a hazard ratio (HR) of 0.82, and reducing the rate of multiple SRE (HR=0.82) in patients with hormone-refractory prostate cancer (HRPC). In May 2010, Amgen submitted a BLA to the FDA for denosumab based on approximately 5,700 patients with advanced metastatic cancer who were enrolled in 3 pivotal, phase III clinical trials (protocol ID: 20050244; NCT00330759, 20050136; NCT00321464, and: 20050103; NCT00321620) evaluating denosumab versus zoledronic acid (Zometa; Novartis). In May 2010, Prolia was approved in the European Union (EU) for the treatment of osteoporosis in postmenopausal women at increased risk of fractures, and for the treatment of bone loss associated with adrogen deprivation therapy (ADT) in men with nonmetastatic prostate cancer at increased risk of fractures. The FDA also approved Prolia for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients with refractory disease or who cannot tolerate other available osteoporosis treatments.
Technology Update
Plastic antibodies
In June 2010, Kenneth Shea, PhD, professor of Chemistry at the University of California Irvine and colleagues, after 20 years of research, have developed 'plastic' antibodies constructed from polymers that mimic their biological counterparts to create a new class of inexpensive therapeutics. In animal tests, these small plastic particles behaved similarly to natural antibodies. In 2008, Shea's group, working with researchers from the Tokyo Institute of Technology, demonstrated for the first time that plastic antibodies made using a technique called molecular imprinting bound to a target as strongly and specifically as natural antibodies. Molecular imprinting involves synthesizing a polymer in the presence of a target molecule. The polymer grows around the target, imprinting it with the target's shape. In order to reproduce the properties of natural antibodies, the investigators tailored their method for making polymers to specifically target large proteins in biologic solutions. In addition to structure-based affinity, researchers incorporate chemical and electrical properties in the polymer while avoiding any potential interactions with other, more common blood proteins. (news link) |
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