Chain Drug Review, March 16th, 2020

DIABETES CARE REPORT Human Stem Cells Converted to Produce Insulin in Mice ST LOUIS Researchers have converted human stem cells into insulin producing cells and demonstrated in mice infused with such cells that blood sugar levels can be controlled and diabetes functionally cured for nine months The findings from researchers at Washington University School of Medicine in St Louis were published online in the journal Nature Biotechnology These mice had very severe diabetes with blood sugar readings of more than 500 milligrams per deciliter of blood levels that could be fatal for a person and when we gave the mice the insulin secreting cells within two weeks their blood glucose levels had returned Blood glucose stayed at normal levels for months to normal and stayed that way for many months said principal investigator Jeffrey Millman assistant professor of medicine and biomedical engineering at Washington University Several years ago the same researchers discovered how to convert human stem cells into pancreatic beta cells that make insulin When such cells encounter blood sugar they secrete insulin Still previous Jeffrey Millman and a close up of insulin secreting beta cells its surrounding environment converting physical cues into biochemical signals Its a completely different approach fundamentally different in the way we go about it Millman said Previously we would identify various proteins and factors and sprinkle them on the cells to see what would happen As we have better understood the signals weve been able to make that process less random Understanding that process has allowed the team to produce more beta cells Importantly the new technique works efficiently across stem cells from multiple sources greatly expanding the ability of this technique in the study of disease We were able to make more beta cells and those cells functioned better in the mice some of which remained cured for more than a year Millman said He explained that there still is much to do before this strategy can be used to treat people with diabetes Researchers will need to test the cells over longer periods of time in larger animal models and work to automate the process to have any hope of producing beta cells that can help the millions of people who require insulin injections to control their diabetes But the research is continuing Forecast Rybelsus a Blockbuster PHILADELPHIA Novo Nordisk AS Rybelsus semaglutide for type 2 diabetes has been listed among 11 new drugs predicted to achieve annual sales of 1 billion or more i e blockbuster status by 2024 The annual Cortellis Drugs to Watch list from Clarivate Analytics PLC includes drugs that are scheduled to enter the market in 2020 The Cortellis team at Clarivate applied its proprietary technologies to produce the list from among drugs that advanced to phase II trials or beyond early this year In January the European Medicines Agencys EMAs Committee for Medicinal Products for Human Use CHMP recommended granting a marketing authorization in the European Union for Rybelsus for the treatment of adults with insufficiently controlled type 2 diabetes to improve glycemic control as an adjunct to diet and exercise It is the first glucagon like peptide GLP 1 receptor agonist treatment a class of non insulin medicines for people with type 2 diabetes developed for oral use providing patients with another option to treat the disease without injections The active substance in Rybelsus semaglutide acts in the same way as the incretin hormone GLP 1 It reduces blood glucose by stimulating pancreatic secretion of insulin and lowering the secretion of glucagon a hormone that works to raise blood sugar concentration when blood sugar is high The safety and efficacy of Rybelsus were studied in eight clinical trials that included patients at various stages of the disease In three of these studies Rybelsus was compared to a placebo In the development program it was either used on its own added to the standard treatment or compared to an injection treatment of its same class GLP 1 receptor agonist The most common side effects observed during the clinical trials were gastrointestinal such as nausea and diarrhea Hypoglycemia may occur when used in combination with insulin or sulphonylurea The opinion adopted by the CHMP is an intermediate step on Rybelsuss path to patient access The CHMP opinion will be sent to the European Commission for the adoption of a decision on an EU wide marketing authorization Once a marketing authorization has been granted decisions about price and reimbursement will take place at the level of each member state taking into account the potential role and use of this medicine in the context of the national health system of that country Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively Most people with diabetes have this form of diabetes Possible complications of diabetes include heart attack stroke kidney failure leg amputation vision loss and nerve damage Rybelsus and the other drugs on the Cortellis list scrutinized by in house analysts researched and evaluated in its individual context by interrogating annual filings drug pipelines clinical trials patents chemistry deals conferences and company announcements and regulatory status This year editors and writers examined the various disease landscapes from all angles analyzed the pricing strategies explored the science underpinning the new medicines to provide reality checks via the ultimate test patients and advocacy groups who will seek beneficiary outcomes from the new drugs The medications listed have been almost universally accelerated in their development by orphan drug status or other designation intended to speed their path to market There is a high level of expectation of commercial success for each despite the fact that most drugs on the list are entering or are poised to enter markets already crowded with competitors meaning theyll face substantial pressures to differentiate themselves Many are expected to tout improved safety versus alternative therapies especially regarding cardiovascular risk while others will seek to highlight novel mechanisms of action or even curative potential work has had its limitations and had not effectively controlled diabetes in mice The researchers have now shown a new technique they developed can more efficiently convert stem cells into insulin producing cells that more effectively control blood sugar A common problem when youre trying to transform a human stem cell into an insulinproducing beta cell or a neuron or a heart cell is that you also produce other cells that you dont want Millman said In the case of beta cells we might get other types of pancreas cells or liver cells Off target pancreas and liver cells dont hurt anything when implanted into a mouse but they dont fight diabetes either The more off target cells you get the less therapeutically relevant cells you have he said You need about a billion beta cells to cure a person of diabetes But if a quarter of the cells you make are actually liver cells or other pancreas cells instead of needing a billion cells youll need 125 billion cells It makes curing the disease 25 more difficult Using the new technique Millmans team found far fewer off target cells were produced while the beta cells that were made had improved function The technique targets the cells internal scaffolding called the cytoskeleton The cytoskeleton is what gives a cell its shape and allows it to interact with Abbott Partners on New Delivery System ABBOTT PARK Ill Abbott will integrate its glucose sensing technology with Insulet Corp s tubeless system the Omnipod Horizon Automated Insulin Delivery AID System to offer personalized automated insulin delivery and care for people living with diabetes Controlled through an app on a users personal smartphone device a unique feature that will be offered with the Omnipod Horizon System the integrated platform will consist of the tubeless insulin delivery pod and Abbotts FreeStyle Libre sensor Through a simple intuitive design glucose data from the sensor will be sent directly to the pod which is embedded with an algorithm to automatically adjust insulin delivery without the need for an additional device connection or tubing This integrated system will be designed to always remain in automated insulin delivery mode and can be controlled through an app on the users smartphone to manually take a dose of fast acting insulin or bolus before meals for optimal performance Additionally the integrated platform is expected to be the first combined system with a fully disposable wearable sensor and pump Abbott is focused on creating future forward health technologies that simplify how people living with diabetes manage their condition so they can live their best lives said Jared Watkin the companys senior vice president of diabetes care As diabetes care becomes more interoperable were developing more connected approaches to improve care Through this partnership Abbott and Insulet will offer an integrated digital health platform that is simple and accurate and will provide a best in class user experience Insulet is excited to expand its partnership with Abbott by building on the Omnipod Horizon platform which offers unparalleled simplicity accuracy and now sensor choice for consumers said president and CEO ShaceyPetrovic Chain Drug Review March 16 2020 59