Posts Tagged AMD
Posted by Darshana V. Nadkarni, Ph.D. in Biotech - Medical Device - Life Science - Healthcare on February 12, 2013
Dr. Mark Shusterman, Medical Director at Oraya Therapeutics, discussed new treatment options for Wet Age Related Macular Degeneration, at http://www.bio2devicegroup.org .
AMD is a leading cause of blindness for seniors, worldwide. In the US, it impacts more people than cataracts and glaucoma combined. It affects 9.1 million people in the U.S. and 10 to 30 million people worldwide. Almost entire medical budget could be consumed by AMD, if the current paradigm for AMD is not solved, said Shusterman.
Biology of the eye is interesting. Normal human eye has two chambers, the anterior and the posterior chamber. Retina has photoreceptors, with the highest concentration of cons that allow us to see color. These are lined at the back of the eye and create electrical impulses that travel through the optic nerve to the brain. The Macula is an oval shaped spot near the center of the retina and is responsible for high resolution central vision. More specifically, it is the fovea, a dimple shaped central part of the macula that produces the highest resolution vision. Retina is the thinnest at this region and most serious forms of macular degeneration affects this area. Risk factors for macular degeneration include, age (60+ years), race (Caucasians and Asians are at greater risk), gender (women are at higher risk), genetics (probability increases, if someone in the family has it), and life style issues (smoking, diet, obesity, and high blood pressure).
Wet form of macular degeneration is a more serious form which is preceded by Dry AMD. Dry AMD is characterized by drusen in the retina and takes years or even decades to develop. It can remain stable or can progress to Wet AMD. About 10-15% of Dry Amd converts to Wet AMD. In Wet AMD, abnormal blood vessels behind the retina start to grow under the macula and these vessels are very fragile and leaky. The oozing blood and fluids accumulate, eventually scarring the rods and the cons. If untreated, it progresses to loss of central vision within 2 years. Signs and symptoms of AMD include, wavy appearance of straight lines, foggy or blurry central vision, difficulty distinguishing colors, development of central blind spot, difficulty reading, and difficulty recognizing faces. Some of the possible ways to prevent AMD are, eating diet rich in vitamins C & E, selenium and carotenoids, taking prescription vitamins indicated for eye health that includes antioxidants and zinc, exercise, not smoking, and maintaining normal BP, weight, and cholesterol.
Often however, there is a disease progression and until now few viable and cost effective treatment options existed. Initially, there were attempts to treat AMD with laser. But it seemed that laser did not just burn scarred tissue, but some good tissue and nerves as well. It appeared, that with laser, slightly less vision loss in the immediate future was traded with more significant vision loss, a year or two later. Another photodynamic therapy or PDT is still around but only seems to work well in certain forms of AMD, but is not effective for most forms of AMD. Anti-VEGF injections, Lucentis, Avastin, Macugen, and Eylea are all in use and have been a standard form of suggested treatment for AMD, since Lucentis was introduced in 2006. Anti-VEGF drugs work by targeting VEGF (Vascular Endothelial Growth Factor), a protein responsible for creation of new blood vessels. But cost and frequency of injections required are major inhibiting factors. For instance, an injection of Avastin costs $50. An injection of Lucentis costs between $1200 and $1400. Most of these anti-vitreal injections work best when given routinely on a monthly basis. Eylea can be given bi-monthly. While the efficacy of anti-VEGF compounds has prolonged and saved the eyesight of millions of patients worldwide, it has also placed a huge new burden on patients who require costly, regular injections, as well as on the ophthalmic practice and on the healthcare systems. And cost constraints render this form of treatment unavailable to many people, across the world. Additionally, although greatly beneficial in stabilizing the progression of wet AMD, and decreasing resulting vision loss, the use of anti-VEGF agents carries significant known risks, such as infection (endopthalmitis), increase in intraocular pressure (glaucoma), stroke and others.
Oraya therapy is a new breakthrough treatment, intended as one-time, non-invasive procedure for Wet AMD. Oraya Therapy uses highly targeted, low-voltage X-rays to inhibit and prevent the growth of abnormal blood vessels under the macula (choroidal neo-vascularization) that is most often associated with wet AMD. Radiation is a useful modality because it targets rapidly proliferating and late responding tissues and cells and unlike ablative therapies like laser photocoagulation, it can deliver small amount of energy to the targeted area like the Endothelium (anti-angiogenic), Fibroblasts (anti-fibrotic), and Inflammatory cells (anti-inflammatory). Non-mitotic cells (such as nerve cells) are left largely unaffected. Slowly replicating cells (such as normally proliferating vascular endothelial cells) generally have time to repair the damage or to be replaced by recruitment from outside the target region.
Oraya Therapeutics I-Ray System comprises of Precision-controlled X-ray tube, Patient interface, patented Eye stabilizing device, Eye tracking module, and Intuitive operator interface. The IRay System is designed to deliver three overlapping X-ray beams to the macula, each 4 mm in diameter. The beams are directed into the eye while the patient sits comfortably in a chair, with the head positioned on a chin rest. The entire procedure takes about 20 minutes and the patient can go home after the appropriate post-treatment evaluations are made. Clinical data indicates that the use of radiation in conjunction with existing pharmacologic therapies may have beneficial results in terms of improved disease control with a decreased need for recurrent intra-ocular injections. Examination of the effects of radiotherapy on wet AMD, in more than one thousand patients, indicated that patients treated with radiotherapy were two times more likely to require no further injections and were overall more likely to require fewer than 4 treatments in a year. The radiotherapy was delivered using high-energy external beam systems (with the exception of one study that used brachytherapy), and doses ranged from 7.5 to 24 Gy. The analysis also determined that no patients suffered radiation retinopathy, optic neuropathy, or malignancy. The presentation was followed by Q&A.
Posted by Darshana V. Nadkarni, Ph.D. in Biotech - Medical Device - Life Science - Healthcare on January 13, 2013
EPPIC 2013 Annual Life Science Conference Highlights
The annual EPPIC Life Science Conference (www.eppicglobal.org) takes place on the day before the start of the J. P. Morgan Healthcare Conference, each year, and offers a forum for information, networking, and mentoring. This year, the conference took place at the Westin SF Airport Hotel on January 6, 2013 and was jointly chaired by Ramani Aiyer, EPPIC President & Principal at Shasta Bio Ventures and Geetha Rao, CEO of Springborne Life Sciences and VP of Corporate Development at Triple Ring Technologies. The Gold sponsors of the event were Global Industry Analysts http://www.strategyr.com, Camargo http://www.camargoblog.com, Merchant & Gould http://www.merchantgould.com, Morrison Foerster http://www.mofo.com, Vivo http://www.vivoventures.com, and WSGR http://www.wsgr.com. Below are the highlights from the conference.
Plenary Talk – Carlos Olguin
The conference opened with plenary remarks by Carlos Olguin, Head of Bio/Nanotechnology/Programmable Matter Group at Autodesk and was moderated by John Cumbers, Head of Synthetic Biology & Resource Utilization in Space at NASA Ames. If you are wondering what has Autodesk to do with life sciences, the talk was an eye opener about interesting things happening on the boundary between bio-nano technology with 3D visualization, simulation, and design. Autodesk professionals bring design and engineering knowledge and look at ways to program matter, through scan, modify, and print pattern, said Olguin. Scan in the case of molecular biology is akin to sequencing DNA, modify refers to modeling, simulation, and optimization and print alludes to synthesizing the DNA. Looking beyond molecular biology, design and engineering in manufacturing as a whole may shift from being top down to self assembled, from being inert to being alive, from being generic to personalized, and from being product oriented to being service oriented, said Olguin. The talk was a clear indication that interesting, cutting edge stuff is happening on the boundaries between disciplines and that is where we will see some breakthrough advances take place in the years to come.
Personalized Medicine Panel
Personalized Medicine Panel was moderated by Sara Kenkare-Mitra, SVP of Development Sciences at Genentech. Brian Naughton, Founding Scientist, 23 and Me, Eric Sasso, VP of Medical and Scientific Affairs at Crescendo Bioscience, and Deborah Kilpatrick, Chief Commercial Officer at CardioDx discussed the implications of efforts in personalized medicine for chronic diseases.
Crescendo Bioscience is a molecular diagnostics laboratory focused on rheumatology. Currently, assessment of rheumatoid arthritis disease activity depends on subjective clinical indicators and is a time consuming process. Crescendo is developing quantitative, objective, biology-based tests intended to provide rheumatologists with deeper clinical insights, said Naughton. The blood test, commercially available since 2010, integrates the concentrations of 12 serum proteins associated with rheumatoid arthritis disease activity into a single objective score to help physicians make more informed treatment decisions.
CardioDx offers Corus CAD blood test that can quickly and safely identify symptomatic patients unlikely to have obstructive coronary artery disease (CAD). However, getting physicians to think differently about using these tests versus imaging based tools, is a challenge, and “we are asking them to trust biology and not just an image”, said Kilpatrick. Currently, 75% of its commercial use is by primary care physicians and about 25% by cardiologists. Cardio Dx works the referral channel from an advocacy standpoint. An additional benefit observed by CardioDx is that after the test, the compliance to statins among patients is dramatically improved. Thus the test leads to a behavior change that would not otherwise occur.
23 and Me has an exciting story and it will again be covered in greater detail in my JPM post. The exciting development is in dramatic reduction of cost. Naughton shared that now it is within the reach of everyone and for $99, any consumer can get all sorts of information about their genetics, including increased risks for diseases like AMD, Alzheimer’s and others The panelists discussed their strategies for broadening the use of their tests with partnership opportunities and for other indications. Hearing about advances in personalized medicine, beyond oncology, was exciting.
Panel on Repurposing of Drugs
Mahendra Shah, partner with Vivo Ventures, moderated the panel that focused on repurposing of drugs. While new drugs cost upwards of $1.1B to develop and bring to market, and take over 10 years, once approved, there is no guarantee that they would be commercially successful, said Shah. The knowledge accumulated, can be analyzed to see the effectiveness of old drug for new usage. NIH is also planning to make an extensive database of old drugs available, to enable scientists to look for new indications.
Ken Phelps, CEO of Camargo Pharmaceutical Services, talked about the regulatory pathway in repurposing of drugs. Camargo specializes in FDA’s 505(b)(2) drug approval process. In 2011, more 505(b)(2) NDAs were approved than 505(b)(1) compounds, said Phelps. Sharing the history of 505(b)(2), Phelps emphasized that currently over 3000 drugs are still on the market that were introduced prior to 1962, when they were not required to be shown to be efficacious, and they are for taking. There are also compounds with new chemical entities and new indications that are available. He observed that it is important to identify compelling commercial differentiation and then take the knowledge available in the public domain, think outside the box, and use it effectively.
Warren Cooper, President at Coalescence was CEO of Prism Pharmaceuticals, a venture backed company that he led from inception to sale of the company to Baxter in 2011. According to Cooper, in repurposing a drug, same criteria should be used as NCE; identification of well defined clinical need, market value, and willingness to adopt and obtain reimbursement, technical feasibility, ability to protect from generics for meaningful period of time, and positive financial justification. What is different from NCE is that compound has a history and sometimes that is helpful and sometimes a hindrance. The deeper the history, the higher the challenge it may cause in the regulatory pathway of repurposing. Cooper discussed the example of injectable amiodarone that was originally developed for use in cardiac arrhythmias and was transferred at Prism Phrama, into NEXTERONE, from IV to ready to use pre-mixed product. The regulatory challenges required rewriting of the label and negotiations with FDA on labeling.
Jaisim Shah, Board Director at Igdrasol, discussed the key drivers for drug repurposing that include, reduction in cycle time, lower cost, better success rate, and quicker ROI for investors. Drug repurposing sales are up, to $20 B this year, said Shah. In 2012, as Chief Business Officer of Elevation Pharma, Shah led the sale of the company to Sunovian for upto $430 million, contingency based deal. The company took glycoyrrolate, a generic drug, approved decades ago by the FDA, and reformulated the compound for use with a nebulizer for chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis. It is found to be a well tolerated, tasteless, and stable formulation.
Panel on Technology Innovations that Shorten Therapeutic Product Development Life-Cycles
Moderated by Mohan Srinivasan, Director at Bristol-Myers Squibb, the panel discussed diverse and new technology adaptations aimed at compressing lifecycle and boosting success rates for drug development. Currently, for each new therapeutic, the product life-cycle ranges between 9 to 15 years and costs over a billion dollars. Can this be significantly shortened by adapting technology advancements in other sectors?
Chunlin Wang is Senior Scientist & Director of Informatics at Stanford Genome Technology Center. In last several years, Wang has been analyzing sequencing data generated by 454 FLX, I1-lumina GAIIx, HiSeq, MiSq, Ion Torrent and Pacific Bioscience platforms for various projects including drug-resistant mutation detection, whole genome sequencing, immune repertoire sequencing, high resolution high-throughput HLA genotyping and new virus discoveries. Using novel sequencing approaches to speed up drug development is one of the best ways to reduce costs, said Wang.
Scott Turner is EVP of R&D at Kinemed Inc. focused on the field of stable isotope research. Turner is leading the research into novel in vivo applications of stable isotopes in diseases. With its patented isotopic tracer technology, Kinemed enables its clients to track key chemical pathways within living systems and look at bio-chemical processes that are targets of drugs. Focusing on study in intact organism provides integrated systems biology information underlying the root causes of disease, said Turner.
Nikesh Kotecha is CEO of Cytobank Inc., a company focused on providing scientific, informatics and software solutions for cytometry. Cytobank focuses on analyzing single cell technologies and has created Cytobank, a cloud-computing platform for flow cytometry data. The Cytobank project grew out of Kotecha’s focus in Dr. Garry Nolan’s lab at Stanford University in developing a diagnostic for juvenile myelomonocytic leukemia and on analysis methods for single cell assays. Thus they take an interdisciplinary approach to address biological and clinical problems to help companies bring together their laboratory bench work and informatics needs. Cytobank is taking this beyond flow cytometry to mass cytometry, for identifying biomarkers, useful in personalized medicine, said Kotecha.
Pradeep Fernandes, co-founder and President of Cellworks Group, was most recently VP and GM of Synthesis Solutions at Cadence Design Systems, following its very successful $120M acquisition of Get2Chip in 2003. Currently, a great deal of data is being generated. Software is a tool that can be leveraged to manage and visualize large data, extract trends, generate insightful data and eventually predict information from large data sets, said Fernandes. CellWorks takes in vivo and in vitro data and clinical trends and tries to build dynamic models that simulate disease phenotypes in computers and can be used to perform mechanistic studies. This information is used to predict effects of new therapy and gain new biological insights regarding toxicity and biological efficacy of drugs. CellWorks has an internal pipeline of therapies and is in collaboration with Astra Zeneca, Genentech and other companies interested in driving selection of therapies.
Speed Pitch, Accent on Youth, Speed Networking
In Speed Pitch, early stage life sciences companies were given the stage for a quick 5-minute pitch about their idea, technology, or company. The companies presented to the entire audience and obtained quick feedback from the distinguished VC panel and gained exposure to showcase to various potential collaborators, partners, and investors. Selected presentations are highlighted on the EPPIC website and other promotional material.
The Youth Panel was An Eppic Annual Conference First. This panel gave an opportunity to budding high school and college age scientists to showcase their outstanding research and later ask questions of each other’s research and future goals etc. The purpose of this panel was to inspire excellence among young people but these exceptionally bright, charming youngsters inspired the audience and left everyone spell bound.
Finally the Speed Networking event gave an opportunity to meet conference attendees in quick three-minute introduction and card exchange rounds.
This was a great conference that provided wonderful networking opportunity and was followed by more relaxed networking and wine reception.