Heart Attack Redefined in International Guidelines

Guidelines issued by the major world cardiology associations to update and standardize just what is a heart attack have added the concept of “myocardial injury.”

The new 4th Universal Definition of Myocardial Infarction emphasizes troponin expression as the main trigger to determine if a person should go to the cath lab for chest pain that may be a heart attack, the authors of the 30-page guideline reported in the European Heart Journal.

Cardiac injury is defined as a rise in troponin without other symptoms or components of myocardial infarction.

“The term acute myocardial infarction should be used when there is acute myocardial injury with clinical evidence of acute myocardial ischemia and with detection of a rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit and at least one of the following:

• “Symptoms of myocardial ischemia”
• “New ischemic electrocardiogram (ECG) changes”
• “Development of pathological Q waves”
• “Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology”
• “Identification of a coronary thrombus by angiography or autopsy”

The guidelines are the 4-year work of a committee representing cardiologists and other healthcare professionals from the European Society of Cardiology, the American College of Cardiology, the American Heart Association, and the World Heart Federation.

“Unless there is clarity in the emergency room on what defines a heart attack, patients with chest pain may be wrongly labelled with heart attack and not receive the correct treatment,” said Kristian Thygesen, MD, of Aarhus University Hospital in Denmark.

“Many doctors have not understood that elevated troponin levels in the blood are not sufficient to diagnose a heart attack and this has created real problems,” said Thygesen, who was joint chair of the Task Force that wrote the document, together with Joseph Alpert, MD, of the University of Arizona in Tucson, and Harvey White, MD, MD, of Auckland City Hospital in New Zealand.

“It is important on several levels to know that what is called a heart attack in Cleveland is also considered a heart attack in London,” Russell Luepker, MD, of the University of Minnesota in Minneapolis, told MedPage Today. “We have tightened up definitions of heart attack categories.”

The new definition also touches on new technologies that include advances in imaging and development of ultra-sensitive troponin assays, noted Luepker, a member of the multi-person task force that worked on the project.

Richard Kovacs, MD, of Indiana University School of Medicine in Indianapolis and vice president of the American College of Cardiology, said the new heart attack definition is needed “because we use these definitions for so much of our quality improvement in our hospitals and clinics.”

He told MedPage Today, “It is important that they have brought back the concept of myocardial injury so we can have a diagnosis of injury not just infarction. That’s a big deal for the patients, because patients with an infarction are treated differently than those with an cardiac injury.”

Kovacs said that have a “crisp definition” of myocardial infarction is also a benefit to doctors, to payers, to regulators, and to researchers, so that when one talks about a heart attack in one institution, it is the same phenomenon occurring to a patient in another facility.

The guideline task force researchers acknowledged the ongoing controversy concerning what troponin assay should be considered to make determination of myocardial infarction.

“Clinicians should be aware that for all cardiac troponin assays, including high sensitivity cardiac troponin assays, there is still no expert opinion or consensus about specific criteria for how the 99th percentile upper reference level should be defined,” they noted.

“We endorse International Federation of Clinical Chemistry and Laboratory Medicine guidelines on the technical issues related to high sensitivity cardiac troponin assays, including how studies should be configured to determine 99th percentile upper reference levels.”

Luepker disclosed relevant relationships with Actelion and Bayer.

Alpert disclosed relevant relationships with AstraZeneca, Johnson & Johnson, Novo-Nordisk and Genzyme/Sanofi Aventis.

Thygesen disclosed relevant relationships with Abbott.

White disclosed relevant relationships with Pfizer, AstraZeneca, Omthera Pharmaceuticals, Eisai, Lultpold, CSL Behring, The Medicines Company, Sirtex Technology, SAHMRI, DalGen Products and Services, Eli Lilly and Company, Sanofi Aventis, and DalCor Pharma UK.

Kovacs disclosed no relevant relationships with industry.

• Primary Source

  European Heart Journal

  Source Reference: Thygesen K et al, “Fourth universal definition of myocardial infarction (2018)” Eur Heart J 2018; DOI: 10.1093/eurheartj/ehy462.

https://bit.ly/2MxDG1U

Affimed shares more than double after $96 million Genentech agreement

Shares of Affimed NV AFMD, +0.00% more than doubled in the extended session Monday after the Germany-based pharma company, which focuses on cancer immunotherapies, said it has entered into an agreement with Roche Holding’sROG, +0.56% Genentech to develop and commercialize immunotherapeutic treatments for multiple cancers. Affimed will apply a proprietary platform which enables antibodies, to “discover and advance” immunotherapeutics of interest to Genentech, Affimed said. Genentech will be responsible for clinical development and commercialization worldwide. American depositary shares of Roche rose 0.1%. “We are incredibly excited to work with Genentech, a leader in oncology with a long history of excellence in the discovery and development of medicines to treat cancer,” Affimed Chief Executive Adi Hoess said in a statement. “This strategic partnership marks an important step on our path to leverage the full potential of innate immune cells in oncology.” Affimed will receive $96 million in an initial upfront payment and other near-term committed funding, and may be eligible to receive up to an additional $5 billion over time, including payments upon achievement of specified development, regulatory and commercial milestones, and royalties on sales. The deal is subject to customary closing conditions, and it is expected to close in the third quarter.

https://on.mktw.net/2oh90n6

Ionis, Akcea hit as the FDA rejects volanesorsen

Ionis $IONS and its sister organization at Akcea have just been slammed with an unexpected rejection of volanesorsen, their drug for regulating plasma triglyceride for patients with rare cases of familial chylomicronemia syndrome.

What happened?

Simply put, we don’t know. All Ionis and Akcea $AKCA did was put out a statement repeating some of their earlier talking points in favor of the drug, which managed to pass muster at the expert panel meeting that was called to review it. They didn’t say why the drug was rejected or what they have to do to win regulators over.

But we can guess.

The agency’s internal review raised some daunting questions about their drug’s safety profile.

In a memo to the advisory committee meeting, James Smith, the deputy director of the Division of Metabolism and Endocrinology Products, spotlighted a general agreement that the drug has a clearly positive effect on regulating plasma triglyceride for patients with rare cases of familial chylomicronemia syndrome. That’s a surrogate endpoint for the disease.

But is the benefit really worth the risk of bleeding, after the drug was linked to sudden an unexpected drops in platelet counts?

Regulators were also somewhat perplexed by Akcea’s wish to switch the dosing regimen and their platelet monitoring strategy to something that was never tested in the clinical trials.

The agency’s expert panel considered those issues, and voted 12 to 8 in favor of an approval — the kind of endorsement that carries particularly heavy weight for rare diseases. As a result, investors weren’t expecting any of this. Akcea’s shares plunged 30% on the news, while Ionis’ stock dived more than 13%.

This morning Alnylam caught a relief rally as it became apparent that Pfizer would have to fight for every inch of their rare disease market niche in ATTR. That left Ionis’ and Akcea’s rival therapy in an uncomfortable third place post.

This day just keeps getting worse for these two closely allied companies, which are very unhappy this evening.

“We are extremely disappointed with the FDA’s decision. FCS is an ultra-rare and debilitating disease. Our disappointment extends to the patient and physician community who currently do not have a treatment available to them. We continue to feel strongly that WAYLIVRA demonstrates a favorable benefit/risk profile in people with FCS as was reflected in the positive outcome from our Advisory Committee hearing in May. We will continue to work with the FDA to confirm the path forward,” said Paula Soteropoulos, Akcea’s chief executive.

https://bit.ly/2wrbML5

Quest unit to buy assets of Provant Health

Hooper Holmes, Inc. d/b/a Provant Health (OTCQX:HPHW) (“Provant Health” or the “Company”), the largest publicly traded, pure-play health and well-being provider in the U.S., today announced that it has entered into an asset purchase agreement with Summit Health, Inc., a subsidiary of Quest Diagnostics (“Quest”), the world’s leading provider of diagnostic testing, information, and services.

Under the asset purchase agreement, Quest will acquire substantially all of Provant Health’s assets and will continue the Company’s service offerings as it has in the past. Throughout the transaction process, Provant Health will continue to serve its customers, remaining focused on meeting customer and partner obligations in the busy fourth quarter season. Upon completion of the transaction, Quest will lend its history, expertise, and resources in the health care space to enhance the experiences of Provant Health’s customers and partners.

Mark Clermont, president of Provant Health, commented, “We believe that the purchase of Provant Health by Quest will extend greater value to our customers and partners than ever before. Quest recognized that Provant Health’s comprehensive services add valuable programs, people and technology to its offerings. Quest’s reach in its space is unrivaled, and its knowledge, resources, and capabilities will only enhance the experiences of those we serve.”

To support Provant Health in meeting its working capital requirements during the sale process, the Company has signed definitive agreements with its two primary lenders, SWK and CNH, to provide up to $13.6 MM, that will allow the Company to continue to operate the business through closing of the sale which is anticipated to be on or before the tenth of October. The Quest asset purchase agreement is valued at $27 million dollars and takes the form of a “stalking horse” bid, with the sale to be completed after an auction process carried out under the terms of section 363 of the bankruptcy code. The Quest asset purchase agreement also contains a transition services agreement “TSA” through December 31, 2018, to ensure a smooth client transition and seamless continued operations.

“After the merger of Hooper Holmes and Provant in 2017, the combined company was saddled with a significant working capital shortfall, an over-leveraged balance sheet and experienced significant losses in 2017. Through this acquisition by Quest, the Company is now positioned for success,” noted Jim Fleet, chief restructuring officer/senior executive in charge of Provant Health.

In conjunction with the sale process, the Company petitioned for Chapter 11 bankruptcy on Monday, August 27, 2018, to facilitate a rapid 363 sale process with an anticipated transaction close date on or before of the tenth of October 2018.

Provant Health underscores its continued commitment to serving its customers and employees as it undergoes this strategic transition.

https://bit.ly/2ws3ykN

Hanger: Amputees meaningful prosthetic mobility not prevented by comorbidities

Published in the American Journal of Physical Medicine and Rehabilitation, MAAT II evaluates largest lower limb prosthetic data set to date

Hanger, Inc. today announced results of the second part of its landmark study of lower limb amputees known as the Mobility Analysis of Amputees (MAAT II). The largest analysis of its kind, the MAAT II study investigated the impact of those comorbidities comprising the Functional Comorbidities Index (FCI) and other notable comorbidities, and their influence on mobility among people living with lower limb loss. MAAT II findings demonstrated a person’s overall comorbid health has little impact on mobility with a lower limb prosthesis as patients with multiple co-morbidities still benefit from a prosthetic device which provides meaningful mobility. The clinical research was peer reviewed and published in a Medline indexed journal, the respected American Journal of Physical Medicine and Rehabilitation.

‘The continued rise in lower limb amputations is creating a need for improved means of identifying patients who will benefit from prosthetic rehabilitation and technology,’ stated James Campbell, PhD, CO, FAAOP, chief clinical officer, Hanger Clinic. ‘In the absence of strong research support to guide prosthetic rehabilitation, decision makers have been restricted in their options for identifying prosthetic candidates. Historically, comorbid health has been among the factors utilized, despite a lack of strong evidence to support this application, which necessitated further research.’

Colleagues in the clinical and scientific affairs department of Hanger Clinic, including James Campbell, PhD, CO, FAAOP, Shane R. Wurdeman, PhD, CP, FAAOP, and Phil M. Stevens, MEd, CPO, FAAOP, performed a retrospective review of outcomes data collected within multiple clinics. The primary endpoint included within the analysis was the Prosthetic Limb Users Survey of Mobility (PLUS-M). Analysis included 596 current prosthetic users, aged 18 or older, with varying amputation levels, including both unilateral and bilateral lower limb amputation.

The results of the MAAT II study found only four factors to be significant predictors of mobility: age, history of stroke, presence of peripheral vascular disease (PVD), and anxiety/panic disorders (R=0.388). With compounding comorbid health conditions, mobility declines.

https://bit.ly/2oe2pJT

Illumina Receives Approval of Sequencing System in China

Enabling Growing Genomic Applications in Chinese Clinical Market

Illumina, Inc. (NASDAQ:ILMN) today announced that its MiSeq™Dx Sequencing System received the approval certificate from the China National Drug Administration (CNDA). This is Illumina’s first CNDA-cleared, next-generation sequencing (NGS) system in China. In accordance with the clearance, Illumina can now market and sell the MiSeqDx Sequencing System to hospitals and other medical institutions for in-vitro diagnostic (IVD) testing throughout China.

Designed specifically for the clinical laboratory environment, the MiSeqDx Sequencing System is a benchtop sequencer that incorporates an easy-to-use workflow and data output tailored to the diverse needs of clinical labs. Taking advantage of proven Illumina sequencing by synthesis (SBS) chemistry, the MiSeqDx Sequencing System provides IVD developers the tools to create accurate diagnostic testing. Additionally, integrated software enables run setup, sample tracking, user management, audit trails and data interpretation.

“The clearance of the MiSeqDx in China is a significant milestone for Illumina because it provides more opportunities for NGS,” said Garret Hampton, Executive Vice President of Clinical Genomics at Illumina. “More medical institutions and patients will now have access to the latest NGS technology. We are encouraging more clinical companies to select the MiSeqDx System to develop new clinical assays and to help provide needed solutions to some of China’s greatest health challenges.”

The MiSeqDx Sequencing System now has regulatory approval in the United States, China, Canada, Argentina, European countries recognizing the CE-IVD mark, Australia, South Korea, Singapore, Thailand and the Philippines.

https://bit.ly/2Pb0DVu

Amgen applies to FDA for once-weekly myeloma combo

Amgen (NASDAQ:AMGN) today announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) to expand the Prescribing Information for KYPROLIS^® (carfilzomib) to include a once-weekly dosing option in combination with dexamethasone (Kd) for patients with relapsed or refractory multiple myeloma. The sNDA is based on data from the Phase 3 A.R.R.O.W. trial, demonstrating KYPROLIS administered once-weekly at 70 mg/m² with dexamethasone (once-weekly Kd) achieved superior progression-free survival (PFS) and overall response rates (ORR), with a comparable safety profile versus the twice-weekly KYPROLIS at 27 mg/m² and dexamethasone (twice-weekly Kd).

The FDA is reviewing the application under the Oncology Center of Excellence Real-Time Oncology Review and Assessment Aid pilot programs, which aim to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible.

https://bit.ly/2oe5MRh