Insulet gets FDA OK on insulin management system

Insulet Corporation (NASDAQ: PODD) today announced FDA510(k) clearance of the Omnipod DASHTM Insulin Management System (Omnipod DASH). This clearance lays the foundation for a steady cadence of innovation that furthers Insulet’s mission to empower users to enjoy simplicity, freedom, and healthier lives with their differentiated technology.

“Omnipod DASH was inspired by Podders and embodies what users on multiple daily injections have been asking for in a diabetes management system,” said Patrick Sullivan, Chairman and Chief Executive Officer. “Our number one priority is to continue to minimize the daily strain on those impacted by diabetes and we are confident this system, and eliminating the system’s upfront cost, do just that.”

Omnipod DASH was built to be simple, discreet and easy-to-use. The system features Bluetooth wireless technology for connectivity between the color touch-screen Personal Diabetes Manager (PDM), tubeless waterproof pump (Pod), and is optimized for use with the CONTOUR® NEXT ONE Blood Glucose (BG) Meter for the seamless transfer of blood glucose readings to the PDM’s bolus calculator. Bluetooth functionality also provides connectivity to the Omnipod DISPLAY™ and Omnipod VIEW™ apps. The DASH PDM will be offered at no cost with the purchase of Pods.

The Omnipod DISPLAY and Omnipod VIEW apps will provide users and their caregivers quick and easy access to their insulin therapy information on their smartphones. Omnipod DISPLAY allows users to discreetly monitor their PDM data on their smartphones along with other Podder-inspired features including “Find my PDM”. Omnipod VIEW allows parents and caregivers to monitor their loved ones’ diabetes more easily and with greater peace of mind. The iOS Today View widget allows users and their care teams to see their or their loved ones’ PDM and continuous glucose monitor (CGM) data on one smartphone screen with one swipe.

Insulet would like to thank the Centers for Devices and Radiological Health (CDRH) branch of the FDA for its collaborative efforts, timely review and ultimate clearance of the Omnipod DASH Insulin Management System submission. Insulet looks forward to working with Captain Alan Stevens and his team as the Company continues to work on its robust innovation pipeline.

Submission for FDA 510(k) clearance of the Omnipod DASH was announced in January, and while today’s clearance allows Insulet to commercialize this product in the United States, the Company is taking a measured approach through a limited market launch to ensure an ideal user experience at full market release. Full market release is estimated to begin in early 2019 in the United States.

https://bit.ly/2Hlq569

Competition on its heels, Blueprint takes three cancer drugs to China

Blueprint Medicines $BPMC is cashing in on the chance to take three of its investigational cancer therapies to China, inking a deal with CStone Pharmaceuticals that gives the Shanghai-based company rights to develop and commercialize the drugs regionally.

The deal gets Blueprint an upfront payment of $40 million, along with $346 million in potential milestones. CStone gets the OK to develop and sell the meds in China, Hong Kong, Macau, and Taiwan — both as standalone therapies or combos.

The three therapies — avapritinib, BLU-554, and BLU-667 — are all investigational kinase medicines that have demonstrated clinical proof-of-concept in certain genomically-defined cancers. BLU-667, an inhibitor designed to target RET fusions to treat NSCLC, had impressed analysts early on. But the drug has recently had to stand up to comparison with Loxo’s rival LOXO-292. Side-by-side comparisons knocked back Blueprints stock at AACR and again during the ASCO preview.

In China, CStone will take on development of these drugs, shouldering the expenses for most of the programs. But the duo are sharing expenses for one trial that will evaluate BLU-554 in a combo with CS1001, a clinical-stage anti-PD-L1 being developed by CStone as a first-line therapy for patients with hepatocellular carcinoma.

“Founded by seasoned executives with deep global and regional development experience and with a growing portfolio of potentially complementary cancer therapies, CStone Pharmaceuticals is an ideal partner in China,” said Jeff Albers, CEO of Blueprint, in a statement. “With recent regulatory reforms in China and the emergence of innovative companies like CStone Pharmaceuticals, we believe this forward-looking collaboration has the potential to expand our ability to address significant patient needs in Greater China while supporting global development of avapritinib, BLU-554 and BLU-667. In particular, we are excited to announce the expansion of the BLU-554 clinical development program in China, where more than half of all new cases of hepatocellular carcinoma worldwide occur each year.”

https://bit.ly/2JhCnOU

FDA reports five more deaths related to intragastric balloons

The U.S. Food and Drug Administration on Monday notified healthcare providers that it had received reports of five more deaths in patients using liquid-filled intragastric balloon systems to treat obesity, bringing the total death toll to 12 since 2016.

The balloon systems associated with the reports are made by ReShape Lifesciences and Apollo Endosurgery, the FDA said.

Shares of Apollo Endosurgery and ReShape were both down about 10 percent in late-afternoon trade.

The FDA said that it was working with the device manufacturers to better understand the issues, and had approved labeling changes last week to reflect information about possible deaths associated with the devices.

Apollo said four deaths had occurred in patients who received the company’s Orbera Intragastric Balloon device since August 2017, when the regulator issued a letter warning healthcare providers of seven patient deaths.

ReShape said there has been one reported death of a patient implanted with a ReShape Balloon since the FDA issued the letter last year.

ReShape said it has not received any product liability-related claims in connection with the death.

https://reut.rs/2LX2cFT

#ASCO18: Pfizer lung cancer med extends survival

Pfizer Inc. (NYSE:PFE) today announced overall survival (OS) data from the ARCHER 1050 trial evaluating dacomitinib as a first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-activating mutations compared to gefitinib. The trial showed a median OS of 34.1 months for patients receiving dacomitinib (95% CI: 29.5, 37.7), representing a more than seven-month improvement compared to 26.8 months with gefitinib (95% CI: 23.7, 32.1). The OS data from ARCHER 1050 were presented today as an oral presentation [Abstract #9004] at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago and have been published simultaneously in the Journal of Clinical Oncology.

“Overall survival is an important measure to assess efficacy of investigational compounds. These data presented today are particularly significant as dacomitinib is the first EGFR tyrosine kinase inhibitor in a Phase 3 head-to-head study comparing two tyrosine kinase inhibitors to show an improvement in overall survival,” said Professor Tony Mok, Chair of Department of Clinical Oncology, The Chinese University of Hong Kong. “I look forward to having dacomitinib as a potential first-line treatment option for non-small cell lung cancer patients with EGFR-activating mutations.”

Overall survival was a secondary endpoint of ARCHER 1050, a randomized, open label Phase 3 study comparing the efficacy and safety of dacomitinib to gefitinib for the first-line treatment of locally advanced or metastatic NSCLC in subjects with EGFR-activating mutations. At the OS data cutoff, median OS was 34.1 months with dacomitinib (95% CI: 29.5, 37.7) compared to 26.8 months with gefitinib (95% CI: 23.7, 32.1). Patients receiving dacomitinib had a 56.2 percent survival rate at 30 months compared with 46.3 percent for patients who received gefitinib. Subgroup analyses were consistent with the primary OS analysis across most baseline characteristics, including patients with common sub-mutations exon 19 and 21.

The adverse events (AEs) observed with dacomitinib in the study were consistent with findings from previous dacomitinib trials. The most common AEs were diarrhea (87%), nail changes (62%), rash/dermatitis acneiform (49%) and mouth sores (44%). The most common Grade 3 AEs with dacomitinib were rash (14%) and diarrhea (8%). Grade 4 AEs occurred in two percent of dacomitinib-treated patients. There was one case of Grade 5 diarrhea and one case of Grade 5 liver disease. The discontinuation rate due to treatment-related AEs for dacomitinib was 10 percent compared to seven percent for gefitinib.

“What is most encouraging about these results is that patients with non-small cell lung cancer harboring EGFR-activating mutations who received dacomitinib achieved a median overall survival of nearly three years, a marked improvement compared to an established treatment in this setting,” said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. “With today’s podium presentation at the American Society of Clinical Oncology annual meeting and the U.S. Food and Drug Administration Priority Review granted earlier this year, we are encouraged by these data and committed to deliver this promising investigational medicine to patients as quickly as possible.”

In April 2018, the U.S. Food and Drug Administration (FDA) granted priority review for dacomitinib for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR-activating mutations. The FDA Prescription Drug User Fee Act (PDUFA) target action date is in September 2018. The European Medicines Agency also accepted the Marketing Authorization Application for dacomitinib for the same indication.

https://bit.ly/2LjDpuq

Potential ‘Achilles heel’ in brain cancer

Paul B. Fisher, M.Ph., Ph.D., F.N.A.I., Thelma Newmeyer Corman Endowed Chair in Cancer Research and member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center

Scientists at Virginia Commonwealth University believe they have uncovered an “Achilles heel” of glioblastoma multiforme (GBM), the most common and deadly form of brain cancer. Their study published this week in the Proceedings of the National Academy of Sciences details how a mechanism that protects glioma stem cells can potentially be exploited to develop new and more effective treatments for GBM.

Autophagy is a process in which cells get rid of unnecessary or dysfunctional components. It can be toxic to the cells, or it can serve a protective role. The researchers demonstrated that protective autophagy allows glioma stem cells to resist anoikis, which is a form of programmed cell death (apoptosis) that occurs when cells detach from the extracellular matrix, or the collection of molecules that helps support and protect cells within the body. The study found that this protective mechanism is regulated by the gene MDA-9/Syntenin.

“We discovered that when we blocked the expression of MDA-9/Syntenin, glioma stem cells lose their ability to induce protective autophagy and succumb to anoikis, resulting in cancer cell death,” says Paul B. Fisher, M.Ph., Ph.D., F.N.A.I., Thelma Newmeyer Corman Endowed Chair in Cancer Research and member of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, chairman of the Department of Human and Molecular Genetics at VCU School of Medicine and director of the VCU Institute of Molecular Medicine. Fisher originally discovered the MDA-9/Syntenin gene, and he and others have shown it to be overexpressed in a majority of cancers.

Fisher, in collaboration with Webster K. Cavenee, Ph.D., Distinguished Professor, Ludwig Institute for Cancer Research, University of California San Diego (UCSD) and other colleagues, found that MDA-9/Syntenin maintains protective autophagy by activating BCL2, a gene that regulates cell death. Additionally, they showed that MDA-9/Syntenin suppresses high levels of autophagy that would be toxic to the cell through epidermal growth factor receptor (EGFR) signaling. Excessive EGFR signaling has been shown to contribute to tumor growth in a wide variety of cancers.

“In the absence of MDA-9/Syntenin, EGFR can no longer maintain protective autophagy. Instead, highly elevated and sustained levels of toxic autophagy ensue that dramatically reduce cancer cell survival,” says Fisher. “This is the first study to define a direct link between MDA-9/Syntenin, protective autophagy and anoikis resistance. We’re hopeful we can exploit this process to develop new and more effective treatments for GBM and possibly other cancers.”

Using GBM cells from patients who underwent surgical removal of their tumors, the scientists demonstrated the loss of these protective biological functions in the absence of MDA-9/Syntenin through laboratory experiments involving glioma stem cell cultures. These findings were then tested in mouse models of human stem cells, where an increase in survival occurred following MDA-9/Syntenin inhibition.

This study builds on an extensive line of research by Fisher and his colleagues into the role of MDA-9/Syntenin in cancer development and progression. Moving forward, they hope to determine if the process they uncovered in this research applies to stem cells from other cancer types. They also plan to continue developing new ways to block the expression of MDA-9/Syntenin. Fisher described one such approach in a recent study demonstrating the effectiveness of an experimental inhibitory drug known as a PDZ1i in reducing MDA-9/Syntenin’s ability to promote invasion of GBM cells in vitro (outside of a living organism) and in vivo (in a living organism).

More information: Sarmistha Talukdar et al. MDA-9/Syntenin regulates protective autophagy in anoikis-resistant glioma stem cells, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1721650115

https://bit.ly/2HkfYyL

#ASCO18: Rare gain for tough-to-treat pancreatic cancer

Patients with pancreatic cancer that hadn’t spread lived substantially longer on a four-drug combo than on a single standard cancer drug, a rare advance for a tough-to-treat disease, researchers reported Monday.

The results indicate the powerful chemotherapy treatment known as folfirinox will likely become standard of care for the minority of patients whose pancreatic canceris diagnosed early enough to be removed by surgery, experts not involved in the study said.

After an average three years of follow-up, almost 40 percent of the folfirinox patients were disease-free compared with about 20 percent who had the standard drug, Gemzar. Overall, almost two-thirds of folfirinox patients were still alive compared with almost half of Gemzar patients, unexpectedly good results, said Dr. Thierry Conroy, the lead author and a cancer specialist at the Cancer Institute of Lorraine in Vandoeuvre-les-Nancy, France.

Results were presented Monday at an American Society of Clinical Oncology conference in Chicago.

Dr. Richard Schilsky, the group’s chief medical officer, called the research an “immediately practice-changing study” and said it’s the biggest advance for pancreatic cancer in 25 years.

Folfirinox is already standard treatment for patients whose pancreatic cancer has spread.

The outlook has been bleak for patients with pancreatic cancer , an uncommon disease for which there is no screening. Symptoms including fatigue, weight loss and abdomen pain often don’t occur until late, after the disease has spread.

About 330,000 cases are diagnosed each year worldwide, including about 55,000 in the United States. About half are diagnosed after the disease has spread; most die within a year of diagnosis and only about 6 percent survive for five years.

About 15 percent of patients are candidates for surgery; generally their disease was detected early and has not spread widely beyond the pancreas.

The new results are “reassuring for a disease where unfortunately on average people only live several months rather than several years. This is a new standard of care for this illness,” said Dr. Andrew Epstein, an expert at Memorial Sloan Kettering Cancer Center in New York.

Nearly 500 patients at 77 centers in France and Canada were enrolled in the study from spring 2012 through fall 2016. They either received the four-drug combo through an IV every two weeks for about six months or Gemzar three times a month for six months. The study was funded by philanthropic groups in France and Canada.

Participants had early ductal tumors, the most common kind of pancreatic cancer.

Side effects are common for both drugs including low blood counts, fatigue and diarrhea, and they occurred more often in folfirinox patients. There was one death in the study in the Gemzar group.

Folfirinox and Gemzar are available as generics. Schilsky said both treatments are “pretty inexpensive” since the drugs are available as generics. Insurance typically covers both for metastatic cancer and gemcitabine for operable cancer, and it’s likely it would cover folfirinox for operable cancer if guidelines are revised and it becomes standard of care, which several experts say is expected.

https://bit.ly/2JfFgzA

Agios leukemia data ‘support frontline use’: Piper

Agios’ ivosidenib combo data support use in frontline AML, says Piper Jaffray. Piper Jaffray analyst Tyler Van Buren noted that the combo of ivosidenib plus Vidaza demonstrated “robust” clinical activity, including the rough doubling of ORR and CR rates compared to Vidaza monotherapy, and he believes the data shared at ASCO are supportive of the combination being used in the frontline AML setting. If these earlier trial results are replicated in the AGILE Phase 3 study, Van Buren sees a high probability of this combo being approved and used in the frontline AML setting, he tells investors. He maintains an Overweight rating on shares of Agios Pharmaceuticals, which are down 5% to $91.92 in afternoon trading.

https://bit.ly/2syoqpm