Cannabis Showing Promise for IBD

Cannabis could be considered to treat inflammatory bowel disease (IBD), investigators said here over the weekend, but the limited evidence on the plant’s efficacy and potential adverse effects necessitates much more research before cannabis becomes a mainstream medicine got IBD.

In addition, a preliminary study showed that consuming cannabis for 8 weeks helped ulcerative colitis (UC) patients.

Speaking at Digestive Disease Week, Mark Silverberg, MD, PhD, of Sinai Health System in Toronto, led a review of evidence on cannabis and IBD, concluding that “when you have exhausted other treatments, it isn’t unreasonable” to try cannabis.

But cannabis can yield adverse effects, he cautioned, especially when consumed by children and adolescents: “It’s not a completely harmless substance.

“It is not clear if cannabis can be used to induce remission in IBD. Further research is warranted to determine if cannabis can be used as an adjunctive therapy to treat symptoms such as nausea, pain, and anorexia,” and to examine the long-term effects.

Right now “we don’t fully understand the endocannabinoid system,” Silverberg said, so it is difficult to manipulate the system with cannabis.

Regarding available evidence, he noted that only three studies have been published to date about cannabis and Crohn’s disease (CD), and one on cannabis and UC. Researchers conducting the CD studies found a higher clinical response rate in the cannabis group, compared with a placebo group, after 8 weeks. There was no difference in clinical remission rates and there was a higher rate of adverse events among cannabis patients. He added that regarding the UC study, the researchers did not divulge any clinical differences after 10 weeks and also recorded more adverse events among cannabis patients.

Silverberg said that cannabis could be an alternative to narcotic medications for IBD patients. In addition, panelists noted after Silverberg’s presentation, cannabis has not caused some of the caustic side effects that narcotics have.

Silverberg said that practitioners should ask themselves if they are aiding their patients: “Are we providing patients what they want? If not, that’s the reason they are seeking out” cannabis independently.

He also cited the following as reasons justifying the use of cannabis to treat IBD:

• There is significant morbidity in young patients with systemic and local symptoms
• Current therapies are effective, but require immune suppression and are often accompanied by adverse events
• A “substantial number” of patients have a desire for complementary and alternative treatments
• There is “ubiquitous” use of cannabis — about one-half of IBD patients use it in some areas, he said
• Cannabis is often applied to reduce abdominal pain, diarrhea, nausea, and anorexia symptoms

Also at DDW, Timna Naftali, MD, of Meir General Hospital and Tel Aviv University in Israel, presented preliminary results of her group’s randomized placebo-controlled trial on cannabis and patients with “moderately active” UC. The researchers divided 28 UC patients who did not respond to conventional medical treatment into placebo and control groups (receiving twice-daily “cigarettes” featuring 0.5 g of cannabis, or about 11.5 mg of THC), and assessed the Disease Activity Index (DAI), Mayo endoscopic scores, and laboratory parameters before and after 8 weeks of treatment.

The control group reported significantly better changes in DAI and Mayo endoscopic scores than the placebo group did. Control patients also reported significantly better improvements in appetite, behavioral change, pain relief, and general satisfaction; placebo respondents reported significantly better improvement in sleep. The laboratory parameters, however, did not improve.

There were no “serious” side effects, the researchers reported, although they did observe statistically insignificant differences in memory decline and dizziness.

The study included 17 males, with a mean age of 33. Patients did not change other medication regimens during the study period.

“Tetrahydrocannabinol-rich cannabis is safe and can induce clinical as well as endoscopic improvement in moderately active UC,” the team concluded.

The study launched in 2010 and just finished, Naftali told MedPage Today, which demonstrates the amount of time it can take to perform the human studies needed to examine cannabis’ potential as a treatment for digestive diseases. She pointed out that numerous animal studies have been conducted, but human studies have been severely lacking.

The results “didn’t surprise me,” she said, explaining that she started the study because she had several patients who were already self-medicating with cannabis and figured she may as well examine it.

She said she hopes the results will fuel future research into medical cannabis for IBD. “It’s not a magic bullet, but it certainly does have an effect, and I think should be explored further.”

• Primary Source

  Digestive Disease Week

  Source Reference: Naftali T, et al “Cannabis induces clinical and endoscopic improvement in moderately active ulcerative colitis” DDW 2018; Abstract Sa1744.

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#ASCO18: Don’t write off IDO yet, says NewLink

At last year’s ASCO, IDO inhibitors were being hailed as the next big thing in cancer immunotherapy, but a series of trial setbacks took that optimism down a notch. Now, armed with new data on its lead IDO drug indoximod, NewLink Genetics insists there is still hope for the class.

Today, the company revealed data from a single-arm phase 2 trial of indoximod given alongside checkpoint inhibitor drugs in 102 patients with advanced melanoma, suggesting that the combination achieved an overall response rate of 56%, with 19% of patients achieving a complete response. The median progression-free survival was greater than one year.

Out of the total group, 70 patients were treated with indoximod alongside Merck & Co’s Keytruda (pembrolizumab), with a small number also receiving Bristol-Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilumumab).

It’s a welcome bit of positive news for NewLink, which has been one of the pathfinders for the IDO inhibitor class. It saw enthusiasm wane however, after a failed phase 3 trial of rival Incyte’s candidate epacadostat paired with Merck & Co’s Keytruda (pembrolizumab)—as well as negative data from other studies including a breast cancer trial with indoximod—was followed by the shuttering of IDO programs at Merck and Bristol-Myers Squibb, among others. It also cost NewLink a $1 billion partnership with Roche on indoximod follow-up navoximod.

While the run of bad news prompted a rethink at NewLink, which is in the midst of a review of all its clinical programs, it would be premature to write off IDO as target, the firm’s chief medical officer Eugene Kennedy, M.D., tells FierceBiotech from the side-lines at ASCO.

The results of the new melanoma trial as well as earlier data in acute myeloid leukemia (AML) and diffused intrinsic pontine glioma (DIPG), a form of brain cancer, are all cause for optimism about the program, he suggested.

“A sizable amount of data has been generated over approximately 20 years describing the central role of the IDO pathway in immune response,” according to Kennedy. “We continue to believe that indoximod, with its unique mechanism of action, may show efficacy in multiple combination therapies across a broad range of cancer indications.”

So what makes indoximod different? According to NewLink, it’s because the drug has a mechanism of action that differs from direct enzymatic inhibitors—a group that includes epacadostat—and may explain its efficacy where other drugs have failed.

“Our work on the MOA of indoximod presented at AACR 2018 suggests indoximod mimics tryptophan, causing the immune cells to sense a normal level of tryptophan and remain active,” said Kennedy. “In so doing, indoximod increases the proliferation of effector T cells, appears to re-program the regulatory T-cells towards helper T-cells, and, finally, downregulates the IDO expression in dendritic cells—activity not seen in the presence of direct IDO inhibitors.”

Kennedy said it is notable that there was a lower percentage of PD-L1 positive patients in the trial, and higher response rates in the PD-L1 negative cohort, than those seen in trials with direct enzymatic inhibitors for patients with advanced melanoma.

Looking ahead, he says the next data read-out will be an update on the phase 1b study of indoximod in combination with radiation and maintenance chemotherapy for pediatric patients with DIPG at ISPNO in July. It will also be presenting updated data from its phase 1b/2 study of indoximod plus standard-of-care chemotherapy for patients with AML at a medical conference at the end of 2018.

“NewLink has generated data in a number of clinical trials suggesting an improvement in response rates and patient outcomes when indoximod is administered in combination with multiple treatment regimens across a number of cancer indications thus far, including PD-1 inhibitors, chemotherapy, and radiation,” according to Kennedy.

“We believe that indoximod’s mechanism may be a contributing factor to the differentiated outcomes of cancer patients.”

https://bit.ly/2kPpyRq

Sony Micronics Gets FDA Clearance for MDx System, E. Coli Test

Sony subsidiary Micronics announced today that its PanNAT microfluidic molecular diagnostics system and related test for Shiga toxin-producing Escherichia coli (STEC) have received US Food and Drug Administration clearance.

PanNAT is a fully automated PCR-based instrument designed to run single and multiplexed nucleic acid amplification cartridges, providing results within an hour without the need for sample preparation. Micronics noted that the battery powered, benchtop-sized platform is designed for use in a diverse range of centralized laboratories.

The STEC test cartridge simultaneously detects and differentiates the stx1 and stx2 Shiga toxins and E.coli O157.

Micronics said the STEC test is its first to receive FDA clearance. CE marking for both the test and PanNAT system is planned, the company added, although it provided no timeframe.

“Micronics believes that the PanNAT system is poised to take advantage of the expanding use of low to medium multiplex assays for timely diagnosis across a diverse group of customers, while also being responsive to the reimbursement environment,” Micronics President Karen Hedine said in a statement.

Sony acquired Micronics in 2011.

https://bit.ly/2kN7OWB

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