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Posts Tagged ‘cancer

Breast cancer screening: How do we maximize benefit while minimizing harm?

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By: Catherine Lerro, Ph.D., M.P.H.

Image by Bruno Glätsch from Pixabay 

Breast cancer is the most commonly diagnosed tumor in US women, and the second leading cause of cancer death in women with an estimated 268,600 diagnoses and 41,760 deaths predicted for 2019. Despite these seemingly sobering numbers, mortality due to breast cancer has declined over the past several decades. Today, women diagnosed with early stage disease are about 99% as likely to be alive five years after their diagnosis as cancer-free women. These declines in cancer death have been largely attributed to both improvements in treatment and successful implementation of mammography (breast x-ray) screening programs, considered a hallmark of preventative cancer care. Some researchers estimate that upward of 380,000 breast cancer deaths have been averted since 1989 due to mammography and improved breast cancer treatment. In fact, the Affordable Care Act has provisions to ensure that women with private health insurance, public health insurance (e.g. Medicare, Medicaid), or health insurance purchased through a state exchange are covered for breast cancer screening. 

The idea behind mammographic screening is that breast cancers diagnosed at an early stage are more likely to respond well to treatment, preventing cancer-related death. While not all cancers have population-wide screening programs, breast cancer is a good candidate for screening. First, breast cancer is common enough to warrant subjecting women to a mammogram at regular intervals during a defined period of known risk. If a disease is very rare, it is likely not a good candidate for population-wide screening because the costs would outweigh the potential benefit. Second, there must be a good test available that is both sensitive and specific. In other words, the test should detect as many true cases as possible, while minimizing the number of patients with false-positives that require more invasive testing such as a biopsy. Finally, there must be some benefit to detecting disease early. For breast cancer, women with early stage disease may be more easily treated and have better prognosis compared to women with distant-stage disease.

Currently, mammograms are recommended for much of the adult female population in the US over the age of 50. Many different organizations release breast cancer screening guidelines on a regular basis including (but not limited to) the US Preventive Task Force, the American Cancer Society, the American College of Obstetricians and Gynecologists, and the American College of Radiology. While the recommendations share some similarities, there are important differences and no one guideline is universally accepted. For example, for women ages 50-74, the US Preventative Task Force recommend biennial mammograms, while the American College of Radiology recommends yearly mammograms. These differences may arise from the data used to develop the guidelines and how the data are valued. For example, the US Preventive Task Force counts mortality reduction as the soul benefit of mammography and considers potential risks such as false-positive tests. The American College of Radiology considers other mammography benefits outside of morality reduction such as less aggressive treatment for early stage cancers. The American College of Radiology also have recently amended their guidelines to consider race, with the option to screen African American women, who are at greater risk of more aggressive breast cancers, starting at younger ages at the discretion of both the patient and physician. 

Understanding how and if breast cancer screening guidelines are integrated into clinical practice is a murkier area still. In recent years, most major guidelines recommend less routine screening and have endorsed a more individualized approach that involves discussion of the benefits and harms of screening and incorporates patient preferences and beliefs, especially for younger women. However, studies have found that despite these changes in recommendations, breast cancer screening in practice in the US has changed very little. This may be driven by US health system traits, such as fee-for-service payment systems and concerns about litigation. Furthermore, both clinicians and patients may overestimate the benefits and underestimate the harms of mammography, particularly for younger women.

The benefits of diagnosing breast cancer early cannot be overstated, as response to treatment and survival depends greatly on stage at diagnosis. However, the potential harms of screening are often overlooked. Of course, there are economic costs incurred for any wide-scale screening program. Just as importantly, we should seriously consider the physical and emotional costs of overdiagnosis and overtreatment. A 2018 report in the Journal of the American Medical Association found that for every 10,000 women screened for breast cancer, more than half under the age of 60 will experience a false positive test result. Almost 10% of women will undergo at least one unnecessary biopsy. Additionally, the authors demonstrated that through screening more women were potentially overdiagnosed (cancers diagnosed and treated that would have never become clinically evident) than deaths were averted. There may be psychological consequences to false positive test results, including both short-term and long-term anxiety. Unnecessary biopsy and overdiagnosis could potentially have long-term physical health consequences that would otherwise be avoided. 

How do we improve mammography screening in the US, maximizing the benefits while minimizing the risks? What is clear is that there is no simple solution. In a health system that largely favors more testing at potential cost to patients, institutional changes in how health insurance reimburses clinicians for care should consider looking beyond fee-for-service models. The newest breast cancer screening guidelines also favor individualized approaches, prioritizing screening among high-risk women and educating patients about the potential benefits and harms of screening with full consideration of their own medical history and preferences. Clinicians may consider tools that utilize detailed patient information to assess an individual patient’s risk of breast cancer, as well as tools soliciting patient preferences that support shared decision-making. Finally, it is important that all women requiring regular mammograms have access to breast cancer screening and high-quality treatment regardless of age, race, geographic location, or socioeconomic status, in order to minimize disparities in stage at diagnosis and breast cancer survival. 

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May 15, 2019 at 11:30 am

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Science Policy Around the Web – February 26, 2019

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By: Jennifer Patterson-West, Ph.D.

Source: Ellsworth Airforce Base

Scientists Release Controversial Genetically Modified Mosquitoes In High-Security Lab

Malaria is a parasitic disease that affects more than 200 million people each year.  Symptoms can range from mild to severe, and include high fever, chills, and flu-like symptoms.  These symptoms are more dangerous to children under the age of 5, which account for 77% of related deaths.

The life cycle of malaria requires two hosts: humans and female Anopheles mosquitoes.  It is important to note that not all species of Anopheles mosquitoes are good vectors, in fact, only 30-40 of the approximately 430 species transmit malaria in nature. The life cycle of malaria is also dependent on additional environmental factors including ambient temperature and humidity. Together these factors account for the geographic distribution of malaria. Although malaria is found more than 100 countries, transmission is most prevalent in Sub-Saharan Africa and in parts of Oceania including Papua New Guinea. 

In the past decade, major gains have been made to control the disease in developing nations thanks to increased funding. Current preventative measures include insecticide-treated netsindoor residual spraying, and intermittent preventative treatment for individuals at increased risk including pregnant women and infants.

In early February, a high-security laboratory in Terni, Italy launched a study to evaluate a new powerful weapon against the mosquito vector.  This new weapon is a genetically modified mosquitothat can spread a genetic mutation lethal to its own species. Researchers targeted the gene “doublesex” to producing female mosquitos that are sterile and have mouths resembling male mosquitos, which are unable to bite.  

The goal is to dramatically crash or reduce the local population of the main species of malaria spreading mosquitoes, Anopheles gambiae. To increase heritability of the mutation, researchers utilized CRISPR technology to engineer a “gene drive” into the genetically modified species. Gene drive inheritance ensures that nearly all progeny inherits the mutation.

Despite the need for new methods for reducing malaria, activists and other scientists warn that the technology can have unforeseen effects on the environment.  The environmental group, Friends of the Earth, is part of international coalition protesting the use of these new genetically modified organisms. Jim Thomas of the ETC group, has noted concern that gene drive technologies can also be used to develop biological weapons.  

To reduce the risk associated with releasing the gene-drive mosquitoes, the project plans years of additional study that will methodically and cautiously evaluate the mosquitoes and their potential environmental impacts with close consultation from other scientists, government officials, and local residents in Africa.

(Rob Stein, NPR)

With one manufacturer and little money to be made, supplies of a critical cancer drug are dwindling

Bacillus Calmette-Guerin (BCG) is a potent immunotherapy for the treatment of fast-growing bladder cancer.  BCG was initially used in 1921 as a tuberculosis vaccine.  In the 1970s, BCG was shown to stimulate the immune system to attack tumor cells when administered through a catheter into the bladder of cancer patients. Since then, BCG has become a potent treatment for intermediate and high-risk non-muscle invasive (NMI) urothelial cancer (UC) of the bladder.

Bladder cancer is the nation’s sixth most prevalent cancer with approximately 80,000 new cases each year.  About 20% of these patients are diagnosed with a type of bladder cancer that can be treated with BCG.  Although BCG doesn’t work for all eligible patients, the response rate is more than 70%.

Despite the established potency of BCG, there is a critical national shortage.  Supplies of BCG have been erratic since 2011, when the United States Food and Drug Administration (FDA) promptly shut down the Sanofi manufacturing lab after a failed inspection.  After continued regulatory issues, Sanofi stopped production of BCG in 2016. Merck is now the only manufacturer of BCG for the Unite States and European markets.

Merck has acknowledged short supplies and indicated that they are currently working at capacity.  Tyrone Brewer, the vice president of global oncology marketing at Merck, has indicated that the company intends to continue producing BCG for “the foreseeable future.”

During shortages, chemotherapies, such as mitomycin, can be used as alternative therapies.  However, they have lower efficacy and a higher price tag than BCG. During the 2014 BCG shortage, the cost of mitomycin increased by 99% further exacerbating the financial burden of these alternative therapies. 

In response to erratic supply of BCG, the Southwest Oncology Group has launched a clinical trial (S1602) to compare the TICE BCG strain currently used in the United States to the Tokyo Strain.  The FDA will consider the results of this trial as critical information for approving the Tokyo strain for use in the United States. 

In the meantime, urologists have begun to divide dosages into thirds to prolong supplies.  However, a recent literature review indicated that a large scale, well-designed, prospective study is need to establish a standard dose and maintenance instillation for reducing recurrence rate since the efficacy of lower dosage is unclear from existing data.

The University of Utah Drug information Service reported that in 2015 approximately 265 generic drugs were in short supply in the United States.  Of potentially greater concern than the current shortage of BCG are generic drugs that can have immediate life and death consequences. For instance, a retrospective study of the norepinephrine shortage in 2011 indicated a 10% higher mortality rate during hospitalization when the alternative vasopressor, phenylephrine was used.

A recent perspective from Davies et al. argues that current policy efforts have not sufficiently prevented supply disruptions of important generic drugs.  A major consideration for dealing with generic drug shortages are the unintended consequences of current policies. For instance, the 2003 Medicare Modernization Act, which sought to protect consumers by limiting the cost increase for generic drugs to 6% above the Medicare average sale price (ASP). This restriction may not provide manufactures with sufficient proficient to invest in production facilities.  

Further compounded these issues is the fact that manufacturers face few negative consequences during shortages, whereas an excess in supply cuts in to profit margins. To provide additional incentive for maintaining reliable supplies of generic-drugs, Davies et al. suggested that the FDA prioritize the review of future generic-drug applications from companies that “maintain generic drug production without quality-control problems”.  In November, the FDA issued a news release about efforts to address drug shortages, which included remedying the underlying problems when a shortage arise within their current authorities.  In today’s political climate, any policy reform or expanse to FDA’s authority to mitigate future shortages and provide incentives for the production of generic medications will require cross-party support. 

(Meghana Keshavan, STAT news)

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February 26, 2019 at 1:44 pm

Science Policy Around the Web – February 6, 2018

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By: Liuya Tang, PhD


source: pixabay

Cancer treatment

Breast cancer treatments can raise risk of heart disease, American Heart Association warns

Common cancer treatments include surgery, chemotherapy and radiation therapy. Chemotherapy and radiation therapy are always applied before or after surgical removal of a tumor, or applied to cancer patients when surgery cannot be performed. Not only will they attack tumor cells, chemotherapy or radiation therapy will also damage normal cells at the same time, which increases risks for other diseases. A recent report in the journal Circulation said that breast cancer treatments can raise risk of heart disease. It has been noticed that “breast cancer survivors who are 65 and older and were treated for their cancer are more likely to die of cardiovascular problems than breast cancer.” The possible cardiovascular consequences of breast cancer treatments may not be new to oncologists, but new cancer treatments have complex side effects which may not fully understood as they work differently from conventional cancer treatments. For example, the newly-developed cancer treatment, immunotherapy, stimulates the patient’s immune system to attack tumors, but sometimes the surging immune response can overshoot its target and attack healthy tissues and organs.

It is not a good idea to stop cancer treatment due to side effects, as saving ones life from a dangerous cancer is critical. But for this double-edged sword, how to make one edge blunt while keeping the other edge sharp? This requires surgeons and oncologists to work together to make a personalized treatment plan. As suggested by Dr. Deanna Attai, a breast surgeon at the University of California at Los Angeles, the patients with less-aggressive tumor may skip chemotherapy based on the test results on the cancer’s risk of recurrence. In addition, adopting different ways to deliver chemo drugs and developing more-targeted radiation can reduce the risks of cardiac damage for breast cancer patients.

It is not solely a doctor’s responsibility to monitor the side effects of cancer treatments, patients also need to be aware of what types of treatments and what the possible side effects are. Wrong treatments of side effects can aggravate symptoms, which may lead to severe problems. The new emerging immunotherapy presents a big challenge to the health care system as the side effects are not thoroughly understood. Doctors’ organizations and nonprofit groups are joining information campaigns to narrow the knowledge gap on immunotherapy, which will help patients better understand procedures of cancer treatment and manage any side effect if it occurs.

(Laurie McGinley, The Washington Post)


Drug development

Racing to replace opioids, biopharma is betting on pain drugs with a checkered past

The opioid epidemic has become a significant problem in the US, as 116 people died every day from opioid-related drug overdoses in 2016. To resolve this issue, biopharma continues to develop pain drugs. The class of drugs are called NGF inhibitors, which were halted by FDA in 2010 due to their severe side effects. NGF is short for nerve growth factor, which is a neuropeptide. When an injury occurs, the production of NGF is increased, which helps the brain perceive the pain. Theoretically antibodies that specifically bind NGF before it reaches cell receptors could be a good choice to inhibit NGF function, therefore treating people with chronic pain. But it was found that NGF antibodies are not suitable for a subset of patients with osteoarthritis, for whom treatment lead to dramatic joint deterioration. To obtain FDA’s approval of entering further clinical trials, drug companies showed that NGF drugs will probably be safe for patients not at risk of joint deterioration and shouldn’t be taken with nonsteroidal anti-inflammatory drugs such as Advil. So the clinical study was resumed in 2015. Will it become a replacement drug of opioids? Will the benefits outweigh its risks? The results will be put on table this year after drug companies finish their Phase 3 studies.


The severity of the opioid epidemic and the high need of non-addictive painkillers have kept drug companies optimistic about developing NGF drugs despite the side effects. However, there are opposite voices. The watchdog group Public Citizen criticized that the side effects are obvious and “further pursuit of testing in humans was an unreasonable course of action”. Criticisms also come from the business side. Leerink analyst Geoffrey Porges has warned Regeneron’s NGF drug would carry “all of the liabilities” of the past and scolded their continuing to pour money into the project. The failure has already been seen in the development of fulranumab, which is one type of NGF antibody. Even if NGF antibodies were approved by FDA, doctors would have concerns for prescribing a medication with potentially dangerous outcomes for patients with certain conditions.

(Damian Garde, STAT News)



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February 6, 2018 at 10:53 pm

Science Policy Around the Web – November 3, 2017

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By: Liu-Ya Tang, PhD


source: pixabay

Cancer Research

Genomic studies track early hints of cancer

Does getting cancer mean the end of the world? No, if it is found early and treated early. Early detection of cancer greatly increases the chances for successful treatment and survival. Researchers have been striving to develop new approaches for diagnosing cancer, as effective screening tests for early detection do not exist for many types of cancer.

Liquid biopsy is one of the new techniques developed in recent years. Different from traditional biopsies which are usually based on tissues, liquid biopsy is a test done on blood, urine or sputum samples. For example, blood based biopsies are to detect circulating tumor cells, DNA or other substances released by tumor cells. One prominent advantage of liquid biopsy over traditional biopsy is that liquid biopsy is less invasive. In addition to being used in cancer diagnosis, liquid biopsy can also monitor a patient’s response to a treatment plan. After several years’ research at the bench, liquid biopsy is now being applied to diagnose and treat cancer patients.

Liquid biopsy can detect cancer at early stage, but some researchers are aiming to detect cancer before its onset. Two recently-funded projects of genomic studies also use DNA sequencing techniques, similar to those used in liquid-biopsy, but they are using the technology to get one step ahead of cancer. To understand the molecular events that trigger benign tumors to become malignant, researchers are interested in creating a “pre-cancer genome atlas” by sequencing DNA from precancerous tissues. This approach will be applied to lung, breast, prostate and pancreatic cancer. It is particularly important for pancreatic cancer as no early detection method is available, leading to high mortality. Moreover, many pancreatic tumors seem to be driven by mutations in the same genes, which could make the disease predictable if known mutations can be detected at the precancerous stage.

As part of the National Cancer Moonshot Initiative, cancer prevention and early detection are as important as cancer treatment in fighting cancer. If the researchers can successfully identify the early hints of cancer development, it would possibly make cancer more predictable or preventable. Avrum Spira at Boston University in Massachusetts, a leader of both projects, believes her work “could herald a change in how researchers approach cancer prevention.”

(Heidi Ledford, Nature News)


The Scientific Workforce

NIH-Funded Network to Foster Diversity: Achievements and Challenges

In October 2014, the National Institutes of Health launched a $250 million diversity initiative, which included a 5-year $22 million grant to support the National Research Mentoring Network (NRMN). The purpose of NRMN is to increase workforce diversity by bringing more historically underrepresented population, which includes blacks, Hispanics and Native Americans, into biomedical research. The mentoring network covers the full spectrum of research community, from undergraduates to senior faculty members. The content of mentoring is not limited to training in grant writing or application, but also various aspects of professional development.

One advantage of NRMN is its expansion of the traditional way of mentoring, where young scientists learn the profession through their contact with supervisors. The mentees could suffer if good mentoring doesn’t come naturally to their mentors or when the extent and quality of mentoring are not tracked. The mentoring needs are particularly high in less research-intensive institutions because potential mentors might be scarce. To overcome these, NRMN was created to provide a mentoring resource to mentees, which is very important to minority students with less access to high quality mentoring. By signing up online, a mentee will be matched by NRMN system based on mentee’s interests and professional goals. As of June 30, NRMN has 3713 mentees and 1714 mentors, compared to only 37 mentees and 16 mentors who signed up during the first year. Demographically speaking, blacks and Hispanics make up 57% of the mentee group compared to only 11% of the Bachelor of Science holders nationwide. NRMN has featured success stories from Rachel Ezieme, who is the daughter of Nigerian immigrants, and Crystal Lee, who is a Native American from the Navajo tribe.

In addition to its success, some challenges still exist. One big challenge is recruiting more mentors. As good mentoring is not directly tied to professional achievement, senior faculty members may not take the extra effort to seek the opportunity to mentor. Dr. Hannah Valantine, who is the National Institutes of Health’s chief officer for scientific workforce diversity, commented that “the burden is enormous”. As evidenced by NRMN data, 58% of the mentors are women, however less than 40% of the tenured faculty positions are held by a woman in the United States. A solution to this could be “tie NIH funding to a university’s commitment to mentoring”, which was suggested by Dr. Karen Winkfield at Wake Forest University in Winston-Salem, North Carolina. A second problem is associated with the evaluation of the program. Dr. Keith Norris, who is leading an official assessment team for NRMN, tries to identify good mentoring and determine which element of NRMN is beneficial for professional development. He said that there’s a large degree of variation in how the mentees and mentors have interacted. Additionally, mentoring relationship can be very short or can last for several years. To address this, Dr. Norris plans to apply “high-touch interventions” and hopes that the results can generalize to the entire population.

(Jeffrey Mervis, ScienceInsider)

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November 3, 2017 at 6:44 pm

Science Policy Around the Web – September 15, 2017

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By: Liu-Ya Tang, PhD


source: pixabay

Public Health

A new flavor in cancer research: sugar

Sugar is an important energy source for fueling our body. However, eating too much sugar doesn’t do any good to our health. It can cause obesity or diabetes, both of which are considered risk factors for cancer. Moreover, there is evidence showing that sugar may play a direct role in cancer development/progression. Here’s why.

The first study is about how sugar protects cancer cells from attack by the immune system. The immune system is the safeguard of our body that acts by cleaning out “foreign” invaders or bad cells. When the cell becomes cancerous, it may disguise itself and escape the challenges imposed by the immune system. Dr. Carolyn Bertozzi’s group at Stanford University found that cancer cells have denser sialic acid, a type of sugar, on the cell surface than that on normal cells. This sugary coating makes cancer cells invisible to the immune system, so they can divide freely in the body. To enable the immune system to attack cancer cells, Dr. Bertozzi proposed to strip away the sugary coating by using drugs.

In addition to masking cancer cells, sugar can also directly promote their growth. Glucose, a metabolic product of sugar, is important for not only the growth of normal cells but also for that of cancer cells. One distinct phenotype of cancer cells is uncontrolled cell growth, which may require more glucose. This notion has been supported by a recent study done by Dr. Jung-whan Kim’s group at The University of Texas at Dallas. The researchers found that high levels of a protein called glucose transporter 1 (GLUT1), which is responsible for transporting glucose, is associated with lung squamous cell carcinoma (SqCC). However, they didn’t observe similar results in lung adenocarcinoma (ADC), which indicates that different cancer cells may adopt different mechanism to satisfy their energy needs. They further found that using GLUT1 inhibitor can suppress the tumor growth in a SqCC mouse model, but not the adenocarcinoma mouse model. Their findings will help the development of specific treatment plans for SqCC patients targeting GLUT1.

The American Heart Association recommended that the maximum amount of sugar consumption for women is 25 grams a day and that for man is 36 grams. However, the reality is that in 2015, on average, each American consumed more than 93 grams of sugar a day. Reducing sugar consumption and eating a balanced diet will not only help decrease the high rates of obesity in the US, but also benefit cancer prevention.

(Erin Blakemore, Washington Post and University of Texas at Dallas, ScienceDaily)

Innovative Technology

Stem cells could help Parkinson’s patients get the dopamine they need

Parkinson’s disease (PD) is a chronic degenerative disorder of the central nervous system that mainly affects movement. It is a progressive disease and PD patients can have very severe symptoms such as the inability to walk or talk. The cause of PD is the death of dopamine-producing neurons, as dopamine, a neurotransmitter, is essential for motor neurons to function properly.

Medications and surgery can help alleviate the symptoms of PD, but there is no cure for it. Recently, a study published in Nature brings hope to doctors, PD patients and their families. This study was led by Dr. Jun Takahashi, a stem-cell scientist at Kyoto University in Japan. As the loss of dopamine is the root cause of PD, to implant dopamine-producing cells to the brain of PD patients would be the most effective way to cure PD. Embryonic stem cells have the versatile ability to develop into different organs, but there are always ethical issues around this research. Dr. Takahashi’s group generated induced pluripotent stem (iPS) cells derived from both healthy people and those with PD, transformed iPS cells to dopamine-making neurons and implanted the cells into monkeys with neurodegenerative disorders. After two years, the monkeys are still alive and the disorder symptoms are greatly mitigated. Dr. Takahashi hopes to begin a clinical trial by the end of next year.

Ideally and in theory, deriving iPS cells from a patient’s own cells would allow them to avoid taking the immune-suppressing drugs that are usually necessary when introducing non-native tissues. But generating customized iPS cells is expensive and requires a couple months for propagation. A good solution, planned by Dr. Takahashi, is to establish iPS cell lines from healthy people and match them with PD patients by using immune cell biomarkers. This approach will probably be feasible as it has been successfully applied in monkeys.

In addition to Dr. Takahashi, there are other scientists conducting stem-cell research on PD. Dr. Jeanne Loring, working at Scripps Research Institute in La Jolla, California, prefers to transplant iPS-derived neurons made from a patient’s own cells. She hopes to start a clinical trial in 2019. Another stem-cell expert from the Memorial Sloan Kettering Cancer Center in New York City, Dr. Lorenz Studer, is working on a trial that will use neurons derived from embryonic stem cells. Although there are still issues in this field, all the efforts will ultimately lead to a better treatment for PD patients. (Ewen Callaway, Nature News)

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September 15, 2017 at 4:05 pm

Science Policy Around the Web – September 5, 2017

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By: Sarah L. Hawes, PhD


Image: By Simon Caulton [CC BY-SA 3.0], via Wikimedia Commons

Gene therapy

FDA approves breakthrough gene therapy for childhood leukemia

Last week, the FDA approved use of gene therapy for the first time, to be used against resistant or relapsed acute lymphoblastic leukemia (ALL) originating in B-cells. The treatment, called Kymriah, was made by Novartis Pharmaceuticals in collaboration with University of Pennsylvania. It is a form of CAR T-cell therapy, in which a patient’s own immune cells are extracted and genetically modified to better identify and attack cancer-laden B-cells before being infused back into the patient.

Because the cellular feature which modified T-cells use to seek and destroy cancerous cells is also present on healthy B-cells, treatment carries risks including hypoxia, hypotension, and suppressed immune function. A life-threatening immunological reaction called cytokine release syndrome appears more commonly in adults, and may explain patient age-restriction (25 and under) on FDA’s approval.

For patients with otherwise intractable cancer, Kymriah may be a literal life-saver. In a recent clinical trial on 63 patients with drug-resistant or recurring ALL, Kymriah lead to remission in 83% of cases three months post-treatment.

While announcing approval of Kymriah, FDA Commissioner Scott Gottlieb asserted that the FDA is “committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.” This has been substantiated for Kymriah in particular using both Priority Review and Breakthrough Therapy mechanisms. These speed FDA approval, thereby shortening pharmaceutical companies’ delay to profit, and have helped to drive activity in the promising CAR T-cell research arena in recent years.

Despite the success of these mechanisms in bringing a breakthrough cancer therapy to market faster, Novartis insists that a $475,000 price tag for one-time treatment is conservative considering the high cost of drug development and low number of candidate patients. This sobering figure is made worse by the fact that some cases indeed recur several months following Kymriah. Novartis is currently working with Medicare on a plan for outcome-based pricing, so that the pharmaceutical company is only paid if patients respond to the therapy.

(FDA News Release; Jessica Glenza, The Guardian)


Image: By NOAA, via Wikimedia Commons

Emergency preparedness

Hurricane Harvey illustrates the importance of disaster preparedness for research institutions (again) 

The US National Academies of Sciences, Engineering, and Medicine released a report just last month highlighting weaknesses in disaster preparedness in biomedical research facilities, and issuing recommendations to enhance the resilience and continuity of research in the face of adversities including natural disasters, fires, and cyber threats. Costs of unpreparedness are high. In In 2012 Hurricane Sandy is estimated to have caused NYU more than $20 million in research equipment, and killed thousands of mice housed in New York laboratories, including many transgenic strains which took decades to develop and existed nowhere else on earth.

Hurricane Harvey’s toll on the scientific community is similarly, incalculably high. University of Houston’s infant rhesus monkeys ran out of formula and had to be weaned early. Loss of refrigeration capability jeopardized precious tissue and reagents, not to mention rendering some agents hazardously unstable. The University of Texas at Austin Marine Science Institute lost the roof off a microbial-ecology lab, forcing trainees to abandon their work and move to alternative institutions.

Some fared better due to advanced planning. For instance, Baylor College of Medicine was protected from Harvey by a wall installed around their campus after 2001 Tropical Storm Allison cost them 60,000 breast-cancer samples and thousands of laboratory animals. To support less fortunate Texas researchers, the broader scientific community has used hashtag #SciHelpTX on Twitter to advertise sharable resources such as open lab space, computers, and animal colony husbandry.

Hopefully Harvey has driven home the message that preparedness is a necessary investment going forward. Enacting preparations remains up to individual institutions’ policies; a list of recommendations by the National Academies can be found here.

(Emma Marris, Nature News)


Image: Wikimedia Commons

Gene therapy

Correction of a pathogenic mutation in human embryos? Maybe! The exploration continues

An August 2017 publication in Nature reports success using CRISPR-Cas9 to delete targeted sections of gene responsible for producing familial hypertrophic cardiomyopathy from human zygotes. The study, led by Dr. Shoukhrat Mitalipov, involved collaboration between the Salk Institute, Oregon Health and Science University (OHSU) and Korea’s Institute for Basic Science. By introducing a short-lived version of CRISPR, an enzyme, and a repair template into a healthy egg prior to fertilization but simultaneously with sperm bearing the targeted genetic defect, authors believe they ensured the gene excisions would take place early, and be carried throughout all following cell divisions. They believe this technique avoids unintended edits and mosaicism, in which both diseased and repaired cells exist side by side in the organism. The team found both the deleted genes and the template for replacement absent, and believe the genome repair used the healthy genes from the egg. They suggest this is due to certain evolutionary resiliencies associated with early stage eggs.

Other researchers responded by emphasizing the remaining uncertainties and importance of maintaining a focus on research as opposed to pushing too quickly toward application of germline editing techniques with the potential for producing heritable genetic changes. Complex ethical questions remain around germline editing even should techniques be perfected for any specific section of the genome. This research could not receive government funding due to the creation and destruction of human embryos.

Within three weeks, a preprint article questioned the likelihood of the egg serving as a template for repair of the genome’s deleted genes. The authors state that following fertilization the egg and sperm DNA are not in close enough contact for such borrowing, and propose two alternative scenarios: Either the egg failed to incorporate the sperm DNA which is sometimes seen with in vitro fertilization, or failed to replace the missing segment at all. Either would have resulted in an absence of the targeted paternal or template genes. Mitalipov has promised to respond point by point.

(Kelly Servick, Science Magazine)

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September 5, 2017 at 5:29 pm

Science Policy Around the Web – July 21, 2017

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By: Rachel F Smallwood, PhD

Source: pixabay


Engineered Cell Therapy for Cancer Gets Thumbs Up from FDA Advisers

A panel of advisers has recommended that the FDA approve chimeric antigen receptor T-cell (CAR-T) therapy for treatment of acute B-cell lymphoblastomic leukemia. The committee unanimously agreed that the risk to benefit ratio was favorable enough to proceed with approval of the drug (tisagenlecleucel), manufactured by Novartis. CAR-T therapy utilizes a patient’s own immune cells to find and attack cancer cells. In a recent trial in humans, 82.5% of patients went into remission following treatment with the drug; there have also been promising results from its use in glioblastoma treatment. The treatment would specifically be for pediatric and young adult patients who did not respond well to initial treatments or who relapsed from being in remission.

Despite have strong positive effects, there are potential risks posed by CAR-T therapy. In the study mentioned above, almost half of the patients experienced an inflammatory reaction called cytokine release syndrome. Although all of those cases were treatable, the condition can be life-threatening. Novartis also reported neurological problems. Other CAR-T trials have had several deaths due to brain swelling, but those were in adult populations and were some differences in the therapies.

The FDA often does take the recommendations of its advisers, but there is much to consider in this decision. It would essentially be approving a living drug that is individualized to each patient; the patients’ own blood cells are sent to a manufacturing center, where they are genetically engineered to target leukemia cells. The cell population is then allowed to proliferate, and the entire process takes around twenty-two days. This process presents a quality assurance and control problem to the FDA. However, the target population typically has a poor prognosis and very few options, so the panel considers the potential for increased survival and quality of life to be worth the risks. (Heidi Ledford, Nature News)

Stem-Cell Therapy

Unapproved Stem-Cell Treatments Touted on Federal Database Clinicaltrials.Gov is an online database, curated by the National Library of Medicine and the National Institutes of Health, that logs clinical studies occurring around the country and allows them to be searched by patients, family members, healthcare providers, and researchers. The information on the site is provided by the researchers or sponsors of the individual studies themselves. It allows patients and healthy people to become aware of opportunities to participate in medical research. These studies involve a wide range of treatments, including drugs, devices, behavioral therapies, and procedures.

A recent study found that the database is being abused by clinics advertising for stem cell trials. These trials target individuals looking for treatment for a variety of conditions, and all of them charge for participation. There are very few FDA-approved stem cell therapies, and most clinics that utilize stem cell therapies assert that they do not need FDA approval since they are practicing medicine and do not substantially alter the stem cells (although that is disputed).  Since the researchers themselves indicate in the database whether they need FDA approval, there is little oversight to ensure these studies are correctly representing the risks and benefits of their treatment.

Although a disclaimer was added this spring that informs visitors that the presence of a trial in the database does not indicate government endorsement of it, many people do not realize that they could potentially be participating in a for-profit procedure that does not have the proper oversight to ensure patient safety. In one such case, three women were blinded who paid to receive stem cell therapy for macular degeneration. Most legitimate research studies will not require payment for participation, although travel and lodging costs associated with participation may be incurred.

While many patients may receive treatment at one of these clinics without an adverse event or even with a positive result, critics of these types of clinics are calling for regulation of entries into the system. They assert that a federal resource for medical research should not be used to advertise for for-profit clinics that are utilizing therapies that have not been studied or reviewed for safety and efficacy. (Laurie McGinley, Washington Post)

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Written by sciencepolicyforall

July 21, 2017 at 10:08 am