Jennifer Barrett, Assistant Editor

Hepatocellular carcinoma (HCC) accounts for more than 90% of all liver cancers. Because of its limited treatment options and poor prognosis, there is currently an unmet need for alternative, more effective therapies. In a new study, researchers have developed a novel peptide drug called FFW that could potentially reduce tumor growth and slow progression of the cancer.

Previous studies have examined SALL4, a protein related to tumor growth, as a prognosis marker and drug target for HCC, as well as other cancers. However, it has been previously classified as an “undruggable target,” according to the researchers.

“In our earlier research, we found out that the SALL4 protein works with another protein, NuRD, to form a partnership that is crucial for the development of cancers such as HCC,” Daniel Tenen, PhD, director of the Cancer Institute of Singapore, said in a press release.

Drug molecules that act on protein interactions such as SALL4-NuRD often require the target proteins to have a small “pocket” in their 3D structure in which the drug molecule can reside and take effect, the researchers wrote.

“Instead of looking for ‘pockets’ on SALL4, our research team designed a bio-molecule to block the interaction between SALL4 and NuRD,” Dr Tenen said in the press release. “In our lab experiments, blocking his interaction has led to tumor cell death and reduced movement of tumor cells.”

This bio-molecule, peptide FWW, is a small chain of amino acids that can interfere with these interactions and effectively block the huge protein-protein interaction surface, without needing a “pocket” to take effect. Additionally, the researchers found that FWW could reduce the growth of Sorafenib-resistant HCC, when used in combination with Sorafenib. 

Targeting the SALL4-NuRD interaction could have important implications for the treatment of HCC, which could translate to a broader range of cancers with elevated SALL4.

“In our latest work, the research team has also demonstrated an effective strategy to accurately target oncogenes previously considered undruggable,” Dr Tenen concluded in the press release. “Moving forward, we hope to investigate how the targeting of these protein interactions might pan out in other cancer types.”

This article was originally published at 

Liu BH, Jobichen C, Chia CS, et al. Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide. 

. 2018. https://doi.org/10.1073/pnas.1801253115

Scientists develop novel drug that could potentially treat liver cancer more effectively [news release]. 2018. https://www.eurekalert.org/pub_releases/2018-08/nuos-sdn080218.php. Accessed August 2, 2018.

Articles

Researchers have developed a novel peptide drug called FFW that could potentially reduce tumor growth and slow progression of liver cancer.

Novel Drug May Help Reduce Tumor Growth, Slow Progression of Liver Cancer

As part of continuing efforts to increase access to generic medications, the FDA took several steps over the past year to promote competition in the market and reduce costs for patients. In 2017, the FDA reached new milestones with its highest number of generic drug approvals in a single month and a historic number of annual approvals, signaling promise for 2018.

Initiatives in the past year that focused on enhancing generic drug policies included published guidance on generic abuse-deterrent opioid development and a policy aimed at expediting the review of generic drug applications for certain products. Moving into 2018, the FDA is continuing to work toward speedier generic drug development and approvals. As part of its Drug Competition Action Plan, the agency has announced additional steps to encourage competition in the generic drug market, according to a statement from FDA Commissioner Scott Gottlieb, MD.

To help speed up the development and review of generic drugs, the FDA released 2 new documents in January 2018 aimed at streamlining and improving aspects of the submission and review process for generic drug applications. It takes the FDA 4 review cycles on average to approve a new drug, sometimes because the application is missing information needed to demonstrate that it meets approval standards, according to the statement. The new guidance will provide developers with key information about what is needed to avoid delays.

“Through today’s guidance, as well as others from the agency, we can achieve one of the FDA’s key goals in 2018, to reduce the number of review cycles, by helping applicants avoid these common deficiencies that lead to review delays and application cycling,” Gottlieb said in the statement.

In one of the published documents, the FDA is formalizing a more streamlined review process, including new templates to make each cycle more efficient. The document establishes practices designed to help guide applicants. For example, if the FDA determines that an Abbreviated New Drug Application cannot be approved in its current form, reviewers must provide more detail to applicants to explain why and outline how this information can be provided.

The goal of this is to guide the FDA’s staff members to work more efficiently in improving review times, according to the statement. “The policies we’ve announced today and those that we’re anticipating in early 2018 represent our ongoing work on the Drug Competition Action Plan, one of the FDA’s highest priorities in 2018,” Gottlieb said in the statement. “In the coming year, we’ll be taking additional steps to improve our own practices and to help guide industry to make sure their generic drug applications can be acted upon as efficiently as possible.”

The number of generic drugs approved by the agency has soared in recent months, with 87 approved in October 2017 compared with 54 approved a year earlier, according to the FDA’s Activities Report of the Generic Drug Program.

 For full-year 2017, the FDA approved a record number, with 1027 approvals.

Gottlieb touted the agency’s progress in a recent “FDA Voice” blog post and expressed similar goals for this year: “We believe that, if current trends continue, we’ll exceed this record number of generic drug approvals in 2018.”

Statement from FDA Commissioner Scott Gottlieb, M.D. on new steps to facilitate efficient generic drug review to enhance competition, promote access and lower drug prices [news release]. January 3, 2018. 

www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm591184.htm

Activities report of the Generic Drug Program (FY 2017). FDA. 

www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/

 ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/ucm584749. htm. Updated November 13, 2017. Accessed January 3, 2018.

Activities report of the Generic Drug Program (FY 2018) monthly performance. FDA. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/ ucm375079.htm. Updated January 3, 2018. Accessed February 1, 2018.

Gottlieb S. Reflections on a landmark year for medical product innovation and public health advances and looking ahead to policy in 2018. FDA Voice. blogs.fda.gov/fdavoice/index.php/2018/01/reflections-on-a-landmark-year-for-med- ical-product-innovation-and-public-health-advances-and-looking-ahead-to-policy- in-2018/. Published January 9, 2018. Accessed January 30, 2018.

In 2017, the FDA reached new milestones with its highest number of generic drug approvals in a single month and a historic number of annual approvals, signaling promise for 2018.

FDA Goals for 2018: Speed Up Generic Drug Approvals, Enhance Competition

The recent resurgence of mumps in the United States may be linked to waning 

 protection, according to a recent analysis from Harvard TH Chan School of Public Health.

Despite decades of declining mumps incidence, due to widespread vaccination, recent outbreaks in vaccinated adults and communities with high vaccine coverage have prompted concerns about the effectiveness of the current vaccine. According to the CDC, from January 1 to February 24, 2018, 32 states and the District of Columbia in the United States reported mumps infection in 304 people. Outbreaks have increased from 229 cases in 2012 to 6,366 cases in 2016.

Outbreaks are troubling, the researchers noted, because mumps infections can cause complications that can lead to infertility, meningitis, and deafness.

 With many of the cases occurring in vaccinated individuals, the researchers aimed to determine whether the resurgence is due to waning immune protection or the emergence of new strains evading the vaccine.

, the researchers pooled and analyzed 6 epidemiological studies of mumps vaccine effectiveness conducted over past decades in the United States and Europe. The researchers estimated that vaccine-derived immune protection against mumps wanes on average 27 years after vaccination, with 25% of individuals in the United States vaccinated losing protection within 7.9 years, 50% within 19 years, and 75% within 38 years.

According to the researchers, a mathematical model of mumps transmission confirmed the central role of waning immunity to the vaccine in the recent resurgence of mumps cases, as well as in outbreaks that occurred in the late 1980s among adolescents. The researchers found no evidence that new strains of mumps virus are contributing to changes in vaccine effectiveness, as new strains would be expected to cause higher incidence among children, not adolescents and young adults.

“Vaccination is the centerpiece of current public health strategy against mumps,” Joseph Lewnard, postdoctoral research fellow at Harvard Chan School’s Center for Communicable Disease Dynamics, said in a press release about the study.

 “Knowing that protection wanes in the long term can help inform how we deploy vaccines to prevent or contain future outbreaks.”

The researchers concluded that routine use of a third vaccine dose at 18 years of age, or booster dosing throughout adulthood, may be one strategy to prevent mumps re-emergence.

The study was funded by the National Institute of General Medical Sciences award U54GM088558 and a Doris Duke Charitable Foundation Clinical Scientist Development award.

Lewnard JA, Grad YH. Vaccine waning and mumps re-emergence in the United States. 

. 2018. Doi: 10.1126/scitranslmed.aao5945

Mumps Cases and Outbreaks. CDC’s website. 

Mumps resurgence likely due to waning vaccine-derived immunity [news release]. Boston. Harvard’s website. 

https://www.hsph.harvard.edu/news/press-releases/mumps-resurgence-waning-immunity/

The recent resurgence of mumps in the United States may be linked to waning vaccine protection, according to a recent analysis.

Study: Mumps Resurgence Due to Waning Vaccine Protection in Adults 

Officials with the FDA have approved Medtronic’s continuous glucose monitoring (CGM) system (Guardian Connect) for use by individuals living with diabetes, according to a company press release.

The Guardian Connect System is indicated for patients aged 14 to 75 years old with diabetes. According to the press release, the product is the first standalone CGM system that can alert patients of potential high or low glucose events up to 60 minutes in advance.

The approval is based on a clinical study that demonstrated the system’s ability to accurately alert patients of 98.5% of hypoglycemic events while using Medtronic’s advanced glucose sensor, Guardian Sensor 3. The Guardian Connect system gives caregivers the opportunity to track glucose in real-time or receive text alerts.

Additionally, the system offers access to the Sugar.IQ smart diabetes assistant, an artificial technology product from IBM Watson Health, which continually analyzes how an individual’s glucose levels respond to their food intake, insulin dosages, daily routines, and other factors.

“Newer sensors paired with intelligent algorithms that help to both predict and understand glucose excursions, particularly hypoglycemia, will make diabetes safer and more comprehensible for people who inject insulin,” Timothy Bailey, director of the AMCR Institute and clinical associate professor at University of California, San Diego, said in the press release. “Greater utilization of smarter CGM systems promises to allow our patients to achieve more glycemic time-in-range and to further reduce the risk of hypoglycemia.”

The Guardian Connect System will be available in the first quarter of Medtronic’s fiscal year 2019 (May 2018-July 2018), according to the press release.

Medtronic Receives FDA Approval for Guardian Connect Continuous Glucose  (CGM) System for People Living with Diabetes [news release]. Medtronic’s website. March 12, 2018. 

http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=2337565

The Guardian Connect System can alert patients of potential high or low glucose events up to an hour in advance.

FDA Approves Smart Continuous Glucose Monitoring System

Emergency department (ED) visits in the United States for opioid overdoses are up, signaling that the epidemic is worsening, according to a recent CDC report.

, the report analyzes data available from ED visits for opioid overdoses across multiple states.

Data from 16 states in the CDC's Enhanced State Opioid Overdose Surveillance Program were examined to identify trends by state and rural/urban differences. The researchers also analyzed data from the National Syndromic Surveillance Program BioSense Platform covering 52 jurisdictions in 45 states. Overall, the researchers found that visits for suspected opioid overdoses rose 30% in the United States from July 2016 to September 2017 across 45 states, and 35% across the 16 states.

These were the key findings from the report:

Eight states from 3 US regions reported substantial increases (25% or greater) in the rate of opioid overdose ED visits.

Significant increases in all states reporting in the Midwest, including Wisconsin (109%), Illinois (66%), Indiana (35%), Ohio (28%), and Missouri (21%).

There was considerable variation among states in the Northeast and Southeast, with some states reporting substantial increases and others reporting modest decreases.

The highest rate of increases (54%) were seen in large central metropolitan areas.

From July 2016 to September 2017, opioid overdoses increased for:

Individuals aged 25-34 (31%), 35-54 (36%), and 55 and over (32%).

Most states (30% average), especially in the Midwest (70% average).

"Long before we receive data from death certificates, emergency department data can point to alarming increases in opioid overdoses," CDC Acting Director Anne Schuchat, MD, said in a press release.

In an accompanying editorial published in the 

, the authors noted that EDs typically do not have consistent protocols or guidelines for what to do after the overdose is resolved. "The CDC Vital Signs report signaled that the ED is a critical entry point for primary and secondary prevention of opioid overdose," they said.

The authors suggested that innovative systems-based protocols can promote overdose education and naloxone distribution. Additionally, initiating medication-assisted treatment with buprenorphine for patients presenting with opioid use disorder, with continuation in primary care, can reduce opioid use.

According to the CDC's report, health care providers can help by prescribing opioids only when benefits are likely to outweigh risks, determining a patient's prescription drug history and level of risk by accessing data from their state PDMP, and identifying mental health, social services, and treatment options for patients with opioid use disorder.

Opioid Overdoses Treated in Emergency Departments. 

. CDC's website. https://www.cdc.gov/vitalsigns/opioid-overdoses/index.html. Accessed March 8, 2018.

Emergency Data Show Rapid Increases in Opioid Overdoses [news release]. CDC's website. https://www.cdc.gov/media/releases/2018/p0306-vs-opioids-overdoses.html. Accessed March 8, 2018.

Houry DE, Haegerich TM, Vivolo-Kantor A. Opportunities for Prevention and Intervention of Opioid Overdose in the Emergency Department. 

. 2018. Doi: https://doi.org/10.1016/j.annemergmed.2018.01.052

CDC: Emergency Department Data Signal Worsening Opioid Epidemic 

In oral testimony before the US House Committee on Energy and Commerce Subcommittee on Oversight and Investigations, FDA Commissioner Scott Gottlieb, MD, urged immediate steps that can be taken to enhance the product of existing licensed influenza vaccines, and he noted that a universal 

The testimony was given hearing on US public health preparedness and response efforts to 

Exploring alternatives to egg-based vaccines is one way to address strain drift or newly emerging strains that make existing vaccines less effective, Dr. Gottlieb said. Many manufacturers are continuing to produce egg-based vaccines, largely because more investment would be needed to fundamentally change manufacturing. Despite this, Dr. Gottlieb indicated that it is worth better understanding the potential of these alternative vaccines.

“Some studies have found that cell-based and recombinant vaccines are more efficacious, or could be more efficacious, than egg-based vaccines; but, more data and analyses are needed,” he said, adding that the FDA is looking at how to develop a more robust recombinant vaccine manufacturing process to increase yield while reducing cost. Additionally, the agency intends to help industry make investments in new manufacturing technologies and develop regulatory tools and guidances for these products.

Data presented at a recent FDA advisory committee meeting suggested that the strains selected for the 2017-2018 vaccine reasonably matched circulating strains, even the H3N2 strain. Past vaccines have also been less effective against H3N2, and Dr. Gottlieb stated that the FDA is trying to better understand why effectiveness tends to be lower against this strain.

FDA Advisory Committee Discusses 2018-2019 Flu Vaccine Strains

Until then, Dr. Gottlieb noted that improving vaccine uptake and preventing shortages of flu treatments, such as antivirals and IV saline, remain essential.

“As we continue to invest in the future of manufacturing and vaccine technology, we also need to remember the importance of simply ensuring that more people are vaccinated with available vaccines each flu seasons,” he explained.

Remarks from FDA Commissioner Scott Gottlieb, M.D., as prepared for oral testimony before the U.S. House Committee on Energy and Commerce Subcommittee on Oversight and Investigations hearing “Examining U.S. Public Health Preparedness for and Response Efforts to Seasonal Influenza.” [FDA Statement]. FDA’s website. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm600244.htm?utm_campaign=03082018_Statement_Oral%20testimony%20flu&utm_medium=email&utm_source=Eloqua. Accessed March 8, 2018.

In oral testimony before the US House Committee on Energy and Commerce Subcommittee on Oversight and Investigations, FDA Commissioner Scott Gottlieb, MD, urged immediate steps that can be taken to enhance the product of existing licensed influenza vaccines.