Category Archives: Diseases

21st Century Cures Act Seeks to Expedite Bench to Bedside New Treatments

 

Author: Louis P. Sintasath, MS, MBA
ResearchDx, Director, Business Development

 
Recently this year the U.S. House of Representatives resoundingly passed a bipartisan resolution, H.R. 6, also known as the 21st Century Cures Act. So what is the 21st Century Cures Act and what is it trying to do? In short, the bill would reauthorize the National Institutes of Health (NIH) through FY2018 and provide $8.75 billion in additional funding through FY2020.

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For proponents of the 21st Century Cures Act, the mission is to improve the lives of every American by bringing innovation to the health care infrastructure, by reducing the time new therapies gets to the clinic, by paving the way for novel discoveries and cures, and by ultimately saving lives.
Internationally recognized as the “contract diagnostic organization,” ResearchDx specializes in the development of companion diagnostics and in vitro diagnostics for the pharmaceutical,biotechnology, research, and diagnostic industries, and is instrumental in new drug development.
According to Philip Cotter, PhD, FACMG, FFSc (RCPA), co-founder and Principal at ResearchDx, an Irvine, California based life sciences company, “The 21 Century Cures Act has long been needed to introduce the growing discipline of Translational Medicine.” Dr. Cotter further explains, “Translational Medicine is a rapidly growing discipline in biomedical research and aims to expedite the discovery of new diagnostic tools and treatments by using a multi-disciplinary, highly collaborative, “bench-to-bedside” approach. Within public health, translational medicine is focused on ensuring that proven strategies for disease treatment and prevention are quickly implemented within the community.”
Title I of the bill focuses on innovation and discovery. It promotes strategic planning for clinical research at the NIH as well as increase accountability at the NIH, reduce administrative burdens, and standardize data in the clinical trial registry data bank. It encourages collaboration among researchers and aims to remove barriers that discourage it. It supports emerging young scientists and establishes an Innovation Fund. The provision also promotes pediatric research through the establishment of the National Pediatric Research Network (NPRN).
The large bulk of the proposed bill lies in Title II. Title II revamps the regulatory processes for innovative drugs and medical devices. This involves the “development and use of patient experience data to enhance structured risk-benefit assessment framework,” says Dr. Cotter. It would also establish a new drug development tool that includes “(1) a biomarker; (2) a clinical outcome assessment; and (3) any other method, material, or measure that the Secretary determines aids drug development regulatory review.” To help advanced qualified drugs, there would be an accelerated approval development plan that includes agreement on surrogate endpoints. This provision has met with some resistance as some have raised concerns that an expedited process may result in increased risk to safety and efficacy.

Title II also lays out a provision on precision medicine, calling for two guidance documents to be added: “General agency guidance and precision medicine” and “Precision medicine regarding orphan-drug and expedited-approval programs.” Modern clinical trial design and evidence development would be implemented as well as a streamlined data review process.

Lawmakers also recognize the need for new antibiotic drug development, inserting a provision that allow for approval of certain drugs for use in a limited population of patients. For breakthrough medical devices where no approved alternatives exist, there will be a new priority review process for premarket approvals (PMA) as well as 510(k) devices. There will also be a formation of a third-party quality system assessment process. There will also be an easing of regulatory burdens for certain Class I and Class II devices.
Title III targets the disparate landscape of electronic health information technology. Title III calls for interoperability standards of electronic health information technology. In addition, the provision also expands the eligibility of telehealth coverage under the Medicare program and calls for the continuing education for physicians. Issues of price transparency are also addressed, along with patient safety and drug abuse prevention under Medicare.

Title IV proposes changes to Medicare and Medicaid to help offset costs of the program. The provision will establish for the first time an upper limit to the payment for durable medical equipment (DME) under the Medicaid program. There will be an incentive to move away from traditional X-Ray imaging to digital radiography. A provision that benefits drug manufacturers involves the ability to exclude authorized generics from the calculation of average manufacturer price (AMP). Because removing the low price of generics from the AMP, the price would be higher and thus the rebate to manufacturers would be higher on brand name drugs. The majority of funding for the program will come from a key provision to drawdown the Strategic Petroleum Reserve (SPR).
H.R. 6 has recently come under intense scrutiny over potential safety and efficacy concerns as well as loosening of FDA standards in the approval process. As the controversies play out in the media and the floor of the Senate, we will have to wait and see what provisions ultimately makes its way into law.

For the full text of H.R. 6, please visit: https://www.congress.gov/bill/114th-congress/house-bill/6/text

Tissue-Specific Molecular Biomarker Signatures of Type 2 Diabetes An Integrative Analysis of Transcriptomics and Protein–Protein Interaction Data

 

 

 

 

Type 2 diabetes mellitus (T2D) is a major global health burden. A complex metabolic disease, type 2 diabetes affects multiple different tissues, demanding a ‘‘systems medicine’’ approach to biomarker and novel diagnostic discovery, not to mention data integration across omics-es (Günther et al. 2014; Montague et al. 2014; Sahu et al. 2014). The two important key determinants of T2D are the failure of peripheral tissues (such as liver, muscle, and adipose tissue) to respond to insulin doses (so-called insulin resistance), and the failure of suitable insulin secretion by pancreatic betacells in response to increased blood glucose levels (Kaiser and Oetjen, 2014).

Mutual DEGs between only two different tissues/cells

Mutual DEGs between only two different tissues/cells

The duration of hyperglycemia caused by failure of betacells also affects insulin secretory capacity, mass, and apoptosis rate of beta-cells, resulting in additional alterations in several processes such as islet inflammation, amyloid deposition, critical B-cell phenotypic alterations (Prentki and Nolan, 2006). On the other hand, the state of hyperglycemia damages nerves and blood vessels, leading to major healthrelated issues such as cardiovascular diseases, stroke, blindness, dental problems, and diabetes-related amputations. Other complications of T2D include enhanced vulnerability to neurodegenerative diseases, presence of various cancer types, pregnancy problems, loss of mobility with aging, and depression (Musselman et al., 2003; Retnakaran et al., 2006).

Due to the high prevalence of T2D and its fateful complications, identifying the genes or genetic factors associated with the development of T2D and elucidating the mechanisms underlying the disease are crucial in prognosis, and development of personalized medicine and therapeutic strategies.

Since it is a polygenic disorder (i.e., multiple genes located on different chromosomes take active roles in the development of the disease), it is better to reveal that gene expression varies more across tissues than across individuals. Several studies reported findings on T2D gene expression profiles of different tissues individually (Kazier et al., 2007; Cangemi et al., 2011; Misu et al., 2010; van Tienen et al., 2012; Dominguez et al., 2011). Despite individual studies exploring T2D specific genes in various tissues, studies considering the meta-analysis of diverse transcriptomics datasets and integrating gene expression profiles with biological networks are very limited.

Keller and co-workers (2008) studied gene expression profiles in eight experimental groups of lean and obese mice.

This article originally appeared in http://www.genengnews.com.  To read the rest of this article click here.

Mutations That May Enable Earlier Diagnosis of Colorectal Cancer Recurrence Identified

A multidisciplinary team of doctors and scientists from Singapore has characterised the genetic changes associated with the spread of colorectal cancer to the liver. This finding is significant in helping to develop personalized diagnostic tests for patients with colorectal cancer based on the genetic changes present in each individual’s colon tumour. The research team comprises representatives from National Cancer Centre Singapore (NCCS), Singapore General Hospital (SGH), Duke-NUS Graduate Medical School (Duke-NUS), A*STAR’s Genome Institute of Singapore (GIS) and Cancer Science Institute Singapore (CSI Singapore) of the National University of Singapore (NUS). The findings were published online in Genome Biology.

Colorectal cancer is Singapore’s most common cancer and incidence rates continue to rise. Most patients are initially diagnosed with an early stage disease. However, a proportion of these patients will develop a recurrence of the cancer (metastasis), typically in the liver, one to three years after their colon surgery. If identified early, the liver metastasis may be amenable to surgical removal, and cure may still be possible.

The Singapore team used leading edge DNA sequencing tools, some of which were developed in-house, including specialised laboratory techniques and computational methods developed at Duke-NUS and GIS to characterise genetic alterations associated with the spread of colorectal cancer to the liver.

Out of 750 genes measured, they found that every individual’s cancer had a unique set of about 15 key genetic mutations. Whilst there was little overlap in the specific mutations present between 2 different patients, the large majority of the mutations found in each patient’s colon tumour were identical to the mutations present in the same patient’s liver metastasis. The team seeks to exploit this biological finding to develop new diagnostic tests in the search and identification of early spread of the cancer based on the genetic information found in the removed cancer from the colon surgery in the first instance.

Cancer survivors dread having their cancer recur. Even if this happens, we still have a chance to cure our colorectal cancer patients provided we diagnose it early. The research findings can have a significant impact on our patients’ quality of life, and improve the precision of the treatment they receive,” said co-author of the study, Assoc Prof Tang Choong Leong, Head, Department of Colorectal Surgery at SGH.

“Based on this study, we intend to customise a diagnostic test for each colorectal cancer individual. We will use the unique set of mutations present in that individual’s cancer, as a barcode or thumbprint that we can exploit as innovative diagnostics to monitor for cancer recurrence and diagnose it early,” explained Dr Iain Tan, co-lead author of the study who is a Consultant Medical Oncologist at NCCS and also a clinician scientist at GIS. The team has been awarded a grant from the National Medical Research Council (NMRC) to further develop this diagnostic test. Dr Tan cautioned that this R&D effort will take several years although he is optimistic that with this finding, further progress could be realized.

This study was performed in partnership with the POLARIS program, a strategic national program funded by A*STAR to translate local research findings towards “fit-for purpose” applications that improve the diagnosis and treatment of diseases in Singapore.

“POLARIS continues to seek opportunities to work with leading local researchers to enable the transition of their research findings from bench to bedside,” explained Prof Patrick Tan from Duke-NUS who is a co-lead author of the study and the Program Director of POLARIS.

Story Source: The above story is based on materials provided by SingHealth. Note: Materials may be edited for content and length.

Monitoring EGFR mutational status in lung cancer patients

SAN DIEGO—Trovagene Inc. announced recently that it has entered into a clinical collaboration with California-based City of Hope to conduct studies to determine the clinical utility of detecting and monitoring EGFR mutations in lung cancer patients using Trovagene’s Precision Cancer Monitoring platform.

Trovagene“Tracking various alterations in the EGFR oncogene, particularly emergence of the T790M mutation, has potential to improve therapeutic strategies for treating patients with non-small cell lung cancer,” said Dr. Mihaela Cristea, lead investigator and associate professor for the City of Hope Lung Cancer and Thoracic Oncology Program. “We look forward to evaluating Trovagene’s molecular diagnostics for the monitoring of circulating tumor DNA found in both urine and blood, with the goal of delivering highly personalized cancer treatment to improve patient outcomes.”

The clinical study is expected to enroll 75 patients with lung cancer. Primary objectives of the study include evaluating concordance between urinary circulating tumor DNA (ctDNA), blood ctDNA and tumor tissue for determining EGFR mutational status. Additionally, the study investigators will evaluate the quantitative and qualitative performance of longitudinal EGFR mutation monitoring using both urine and blood specimens, as they relate to response to therapy over time. Exploratory objectives include evaluating the feasibility of identifying the TKI-resistant mutation, T790M, in urinary and blood ctDNA at the time of progression.

“Enabling physicians to detect the emergence of problematic mutations in real-time is a key benefit of our Precision Cancer Monitoring platform, and one such mutation is EGFR T790M, which drives treatment resistance in non-small cell lung cancer patients,” said Dr. Mark Erlander, chief scientific officer of Trovagene. “This is an important part of our strategy to realize the full potential of our platform, as we partner with major cancer treatment centers in the U.S. to obtain clinical utility data and to integrate our technology into clinical practice.”