In Type 2 Diabetes, Bariatric Surgery Is Tops for Vascular Risk Reduction

Bariatric surgery reduced microvascular disease risk in patients with type 2 diabetes compared with usual care, according to new research.

In a large retrospective cohort study, only 16.9% of adults with type 2 diabetes who underwent bariatric surgery developed microvascular disease 5 years postoperatively, compared with 34.7% who received only usual diabetes care (adjusted HR 0.41, 95% CI 0.34-0.48), reported David Arterburn, MD, MPH, of the Kaiser Permanente Washington Health Research Institute in Seattle, and colleagues.

As noted in the team’s study in the Annals of Internal Medicine, individuals who underwent bariatric surgery — including gastric bypass, sleeve gastrectomy, or adjustable gastric banding — had a lower risk for several microvascular conditions 5 years after surgery:

• Diabetic Neuropathy: 7.2% [surgery] versus 21.4%; HR 0.37 (95% CI 0.30-0.47)
• Nephropathy: 4.9% versus 10.0%; HR 0.41 (95% CI 0.29-0.58)
• Retinopathy: 7.2% versus 11.2%; HR 0.55 (95% CI 0.42-0.73)

These reductions in microvascular disease risk were significantly lower even just 1 year after surgery, with a 62% reduction in risk for incident microvascular disease seen among those who underwent bariatric surgery (HR 0.38, 95% CI 0.33-0.44), the team said. Even only after 1 year, these patients saw a significant risk reduction for incident diabetic neuropathy (HR 0.28, 95% CI 0.23-0.35), nephropathy (HR 0.29, 95% CI 0.21-0.42) and retinopathy (HR 0.64, 95% CI 0.52-0.79).

Interestingly, the researchers said, these reductions in microvascular disease risk were largely maintained even 7 years after surgery, with a 60% risk reduction for incident microvascular disease (HR 0.40, 95% CI 0.30-0.53). The risk for incident diabetic neuropathy, nephropathy, and retinopathy were also still significantly lower after 7 years compared with usual care — marked by a 52% (95% CI 0.34-0.67), 55% (95% CI 0.29-0.71) and 63% (95% CI 0.24-0.58) reduced risk, respectively.

The matched cohort study included 4,024 adults with type 2 diabetes and severe obesity, marked by a body mass index (BMI) of 35 or greater, who underwent bariatric surgery. The majority of these patients underwent gastric bypass (76%), while 17% underwent a sleeve gastrectomy and 7% received an adjustable gastric band. These individuals were matched with 11,059 individuals from four integrated U.S. health systems who also had type 2 diabetes and severe obesity but received usual care.

Arterburn and co-authors said that although not all patients will be initially interested in bariatric surgery to treat their type 2 diabetes, healthcare providers can engage all patients who have type 2 diabetes and a BMI of 35 or greater in a “shared decision-making conversation about the benefits and risks of bariatric procedures.”

“Our results add to a growing body of evidence suggesting that bariatric surgery not only improves glucose, blood pressure, and lipid control but is likely to reduce macrovascular and microvascular complications, as well as improve survival, in patients with severe obesity and [type 2 diabetes],” the team wrote, adding that the findings add to the 5-year outcomes of the STAMPEDE trial, which reported similar risk reductions in microvascular outcomes for these patients.

The study was praised in an accompanying editorial by Carel le Roux, MD, PhD, of the University College Dublin, and Philip Schauer, MD, of the Cleveland Clinic, who noted that the mortality rate from type 2 diabetes is largely driven by related complications, such as microvascular disease.

Limitations of the study, le Roux and Schauer added, were the use of electronic health records and that it was not randomized. They called for a randomized controlled trial and suggested that future studies look at new surgical procedures, medical devices, and other combinations of medications plus devices, beyond simply improving glycemic control.

“We can now consider surgery a treatment of diabetes beyond glycemia,” the editorialists concluded. “Bariatric surgery can now be intended to prevent complications of type 2 diabetes.”

The study was supported by an award from the National Institute of Diabetes and Digestive and Kidney Diseases. Schroeder and O’Connor were also supported by awards from the National Institutes of Health.

Arterburn reported grants from the Patient-Centered Outcomes Research Institute during the conduct of the study, grants from the National Institutes of Health outside the research and relationships with the Michigan Bariatric Surgery Collaborative outside the study.

Le Roux reported relationships with the Science Foundation Ireland, Health Research Board, NovoNordisk, GI Dynamics, Eli Lilly, Johnson and Johnson, Sanofi Aventis, Astra Zeneca, Janssen, Bristol-Myers Squibb, and Boehringer-Ingelheim.

Schauer reported relationships with Ethicon, Medtronic, Pacira, Novo Nordisk, The Medicines Company, Neurotronic, and AMAG.

• Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine (Retired), Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse Planner

• Primary Source

  Annals of Internal Medicine

  Source Reference: Arterburn D, et al “Microvascular Outcomes in Patients With Diabetes After Bariatric Surgery Versus Usual Care” Ann Intern Med 2018; DOI: 10.7326/M17-2383.

• Secondary Source

  Annals of Internal Medicine

  Source Reference: Le Rou, C, Schauer P “Prevention Is Better Than Cure: The Next Frontier for Bariatric Surgery?” Ann Intern Med 2018; DOI: 10.7326/M18-2114.

https://bit.ly/2LUkdIi

Mapmygenome Partners With Blockchain Startup Digital DNAtix

 Indian consumer genomics company Mapmygenome is partnering with blockchain genetics startup Digital DNAtix to provide extra security and privacy for its direct-to-consumer genetic tests. The blockchain technology also will allow researchers to access anonymous data for their work, the companies said.

Digital DNAtix, of Ramat Gan, Israel, will provide Mapmygenome with a platform to offer its genome testing, analysis, and related personalized medicine services in a faster, more secure environment than previously available.

“Anyone can anonymously upload partial and/or full genome sequences onto the DNAtix platform, and then have access to to their genomic data which they can use to make informed decisions,” Digital DNAtix CEO Ofer Lidsky said in a statement.

“It opens doors to a much larger audience base, and adds another layer of security with the promise of blockchain in addition to our secure lab information management systems,” added Anu Acharya, CEO of Hyderabad, India-based Mapmygenome. “By utilizing DNAtix’s blockchain-based platform for furthering the availability and accessibility to genomic services globally, we are taking yet another step towards empowering the masses with the promise of personal genomics — a doorway to preventive, predictive, personalized, precise medicine.”

Mapmygenome, which launched in 2013, raised $1.1 million in an early financing round in 2015. The company reportedly raised an additional $20 million in 2016.

https://bit.ly/2ngHwgJ

Lawsuit Against Illumina, Thermo Fisher, Others Alleges Fraud, Trade Secre Theft

A lawsuit filed last Friday has made sweeping claims of trade secret theft and fraud against Illumina, Thermo Fisher Scientific, Affymetrix, and individuals in the genomics industry.

Monib Zirvi of Weill Cornell Medicine; Matthew Lubin, now an internist but previously director of medical genetics at Strang Cancer Prevention Center; and Maria Kempe of Lund University filed the suit in the US District Court for the Southern District of New York.

In the lawsuit, the plaintiffs allege that the defendants misappropriated technology the plaintiffs developed including improved primers and probes for various types of PCR reactions and ligase detection reactions, as well as universal arrays for identifying nucleic acids or DNA changes.

Zirvi, while a doctoral student in Francis Barany’s lab at Weill Cornell Medicine originally developed “zip code” sequences to be used in universal DNA arrays that he and other researchers, including Lubin, described in a grant proposal to the National Cancer Institute. Kempe, meantime, according to the suit, developed technology relating to surface and linker chemistry for arrays while she was a postdoctoral researcher in George Barany’s lab at the University of Minnesota.

The lawsuit first accuses Stephen Fodor, who at the time was chief technology officer at Affymetrix and was one of the peer reviewers of the Barany team’s grant proposal, of obstructing the researchers from getting the grant and of then trying to re-patent the idea at Affymetrix. In addition, it alleges, that Affymetrix went on to submit and obtain a $30 million grant from the National Institutes of Standards and Technology soon after reviewing the Barany team’s proposal.

The suit further accuses the founders of Illumina of also submitting multiple patent applications that appropriated the plaintiffs’ technology. The suit describes in detail efforts by Zirvi to track down instances in Illumina patent applications where it alleges Illumina changed words in order to obfuscate that the claimed invention originated from the Barany team. And it alleges that Illumina’s SNP genotyping arrays as well as its AmpliSeq for Illumina reagents infringe on the zip code sequence technology as well as a number of patents originally assigned to Barany.

A number of the patents included in the suit were also the subject of a prior lawsuit jointly brought by Cornell and Thermo Fisher against Illumina. Illumina and Thermo Fisher settled the suit last year, but Cornell is seeking to rescindthat settlement.

In total, the lawsuit includes 12 counts, alleging the defendants violated the Defend Trade Secrets Act, misappropriated trade secrets, committed racketeering, breached fiduciary duties, submitted false and misleading patent applications, and deprived the plaintiffs of economic advantages, and committed civil conspiracy.

The plaintiffs have requested a trial by jury and for the defendants to disclose all cases in which they are using the plaintiffs’ trade secrets and to return all information related to those trade secrets. In addition, they have requested compensatory damages, punitive damages, and for the defendants to be liable to the plaintiffs.

https://bit.ly/2MmkxeZ

Jazz, MD Anderson Collaborate to Evaluate Blood Cancer Treatments

 Jazz Pharmaceuticals, Inc. (Nasdaq: JAZZ) and The University of Texas MD Anderson Cancer Center today announced a five-year collaboration agreement with a goal of evaluating therapies for multiple hematologic malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndromes.

The joint effort brings together MD Anderson’s translational medicine and clinical research capabilities with Jazz’s hematology/oncology portfolio, including its FDA-approved medicines as well as current and potential future investigational therapies.

“This collaboration represents a significant opportunity to efficiently develop innovative therapies and therapeutic combinations,” said Tapan Kadia, M.D., associate professor of Leukemia at MD Anderson. “Our aim is to always provide leading-edge care for our leukemia patients, and it is our hope that this joint effort will result in new treatment solutions.”

Jazz and MD Anderson will pursue research opportunities in areas of high unmet need. The initial focus of the collaboration is to evaluate and generate additional data for Vyxeos^®(daunorubicin and cytarabine) liposome for injection, in new patient populations and in combination with other therapies.

“Jazz is committed to providing meaningful medicines for people with hematologic cancers, particularly those with serious unmet clinical needs,” said Allen Yang, M.D., Ph.D., vice president and acting chief medical officer of Jazz Pharmaceuticals. “We look forward to collaborating with MD Anderson to help advance treatment options for patients as part of our growing hematology oncology therapeutic area.”

Vyxeos received FDA approval in August 2017 for the treatment of adults with newly-diagnosed therapy-related (t-AML) or AML with myelodysplasia-related changes (AML-MRC), which represents part of high-risk or secondary AML populations. AML-MRC is more common in older patients who often do not respond well to intensive chemotherapy; while t-AML can occur as a result of previous chemotherapy or radiation therapy.

https://bit.ly/2OhEBQn

Teva move lower attributed to Celltrion inspection letter

Shares of Teva Pharmaceutical moved lower heading into the close, which is being attributed to an FDA inspection letter that was sent to Celltrion following an inspection conducted on July 9-17. RBC Capital analyst Randall Stanicky has previously said on March 26 that he was concerned about fremanezumab given Celltrion’s outstanding warning letter. In October of 2016, Celltrion and Teva had announced that the companies entered into an exclusive partnership to commercialize two of Celltrion’s mAb biosimilar candidates in the U.S. and Canada.

https://bit.ly/2Mlr1eo

Gemphire: FDA asks for additional data regarding partial clinical hold

Gemphire Therapeutics announced that the U.S. Food and Drug Administration has requested that the company produce data from a sub-chronic toxicology study to provide information to support lifting the partial clinical hold on gemcabene with respect to clinical trials of longer than six months in duration. The FDA also informed the Company that the End of Phase 2 meeting, and consequently the initiation of Phase 3 trials investigating gemcabene in dyslipidemia indications and long-term safety exposure trials needed for registration, will not take place until the partial hold has been lifted. Gemphire’s ongoing Phase 2a proof-of-concept studies investigating gemcabene as a treatment for familial partial lipodystrophy and for pediatric NAFLD are not affected by the FDA’s request for additional data and the Company continues to expect that these studies will produce top-line interim data in late 2018 and in the first half of 2019, respectively. In addition, the Company continues to be free to conduct clinical trials that do not extend beyond six months in duration. Beginning in 2004, the FDA began issuing partial clinical holds to all sponsors of PPAR agonists or agents deemed to have PPAR-like properties from preclinical studies. The FDA takes the position that PPAR agonists are potential liver toxins, but recognizes that rodent observations are often not relevant to humans. In 2004, the FDA determined that gemcabene has PPAR agonist properties and issued a partial clinical hold. In response the FDA has requested that, as part of a complete response, Gemphire must provide additional data including a subchronic (13 week) study in PPARalpha knock-out mice and PPAR transactivation assays using monkey and canine PPAR isoforms, to further understand the human relevance of the preclinical findings. The Company has initiated plans to conduct these required studies and expects to submit the additional results to the FDA in the second quarter of 2019. “We are working closely with the FDA to release the partial clinical hold on gemcabene, with the goal of proceeding to an End of Phase 2 meeting and reaching agreement on the design of a Phase 3 clinical program,” said Dr. Steven Gullans, CEO of Gemphire. “Our confidence in gemcabene’s safety profile is supported by the fact that it has been observed to be safe in nearly 1,200 human subjects in 24 Phase 1 and 2 clinical trials. In fact, gemcabene’s safety performance in previous human clinical provided the basis for the FDA to allow the agent to be evaluated in a multi-center, investigator-led ongoing NAFLD trial in pediatric patients. “In the meantime, we are continuing to execute on our ongoing Phase 2a POC clinical trials of gemcabene in NAFLD/NASH. Gemphire is well capitalized, with $28 million cash on hand as of June 30 2018. Based on current projections, taking into account the delay of significant cash expenditures for clinical trials and manufacturing and the amended terms of the loan agreement with SVB, we believe we have sufficient resources to fund operations into the fourth quarter of 2019.”

https://bit.ly/2OhAuUr

ObsEva initiated at Wedbush

ObsEva initiated with an Outperform at Wedbush

https://bit.ly/2OJnhVs