Food allergy is associated with lower risk of SARS-CoV-2 infection

 A National Institutes of Health-funded study has found that people with food allergies are less likely to become infected with SARS-CoV-2, the virus that causes COVID-19, than people without them. In addition, while previous research identified obesity as a risk factor for severe COVID-19, the new study has identified obesity and high body mass index (BMI) as associated with increased risk for SARS-CoV-2 infection. In contrast, the study determined that asthma does not increase risk for SARS-CoV-2 infection.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) study also found that children ages 12 years or younger are just as likely to become infected with the virus as teenagers and adults, but 75% of infections in children are asymptomatic. In addition, the study confirmed that SARS-CoV-2 transmission within households with children is high. These findings were published today in the Journal of Allergy and Clinical Immunology.

“The HEROS study findings underscore the importance of vaccinating children and implementing other public health measures to prevent them from becoming infected with SARS-CoV-2, thus protecting both children and vulnerable members of their household from the virus,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy, and Infectious Diseases (NIAID), part of NIH. “Furthermore, the observed association between food allergy and the risk of infection with SARS-CoV-2, as well as between body-mass index and this risk, merit further investigation.” NIAID sponsored and funded the HEROS study.

Tina V. Hartert, M.D., M.P.H, co-led the research with Max A. Seibold, Ph.D. Dr. Hartert is director of the Center for Asthma and Environmental Sciences Research, vice president for translational science, the Lulu H. Owen Chair in Medicine, and a professor of medicine and pediatrics at the Vanderbilt University School of Medicine in Nashville. Dr. Seibold is director of computational biology, the Wohlberg and Lambert Endowed Chair of Pharmacogenomics, and a professor of pediatrics in the Center for Genes, Environment, and Health at National Jewish Health in Denver. 

The HEROS study team monitored for SARS-CoV-2 infection in more than 4,000 people in nearly 1,400 households that included at least one person age 21 years or younger. This surveillance took place in 12 U.S. cities between May 2020 and February 2021, before the widespread rollout of COVID-19 vaccines among non-healthcare workers in the United States and before the widespread emergence of variants of concern. Participants were recruited from existing, NIH-funded studies focused on allergic diseases. Roughly half of the participating children, teenagers and adults had self-reported food allergy, asthma, eczema, or allergic rhinitis. 

A caregiver in each household took nasal swabs of participants every two weeks to test for SARS-CoV-2 and filled out weekly surveys. If a member of the household developed symptoms consistent with COVID-19, additional nasal swabs were taken. Blood samples also were collected periodically and after a family’s first reported illness, if there was one.

When the HEROS study began, preliminary evidence from other research suggested that having an allergic disease might reduce a person’s susceptibility to SARS-CoV-2 infection. The HEROS investigators found that having self-reported, physician-diagnosed food allergy cut the risk of infection in half, but asthma and the other allergic conditions monitored—eczema and allergic rhinitis—were not associated with reduced infection risk. However, the participants who reported having food allergy were allergic to three times as many allergens as the participants who did not report having food allergy.

Since all these conditions were self-reported, the HEROS study team analyzed the levels of immunoglobulin E (IgE)-specific antibodies, which play a key role in allergic disease, in blood collected from a subset of participants. A correspondence between self-reported food allergy and food allergen-specific IgE measurements supports the accuracy of self-reported food allergy among HEROS participants, according to the investigators.   

Dr. Hartert and colleagues speculate that type 2 inflammation, a characteristic of allergic conditions, may reduce levels of a protein called the ACE2 receptor on the surface of airway cells. SARS-CoV-2 uses this receptor to enter cells, so its scarcity could limit the virus’s ability to infect them. Differences in risk behaviors among people with food allergy, such as eating out at restaurants less often, also could explain the lower infection risk for this group. However, through biweekly assessments, the study team found that households with food-allergic participants had only slightly lower levels of community exposure than other households.

Previous studies have shown that obesity is a risk factor for severe COVID-19. In the HEROS study, investigators found a strong, linear relationship between BMI―a measure of body fat based on height and weight―and the risk of SARS-CoV-2 infection. Every 10-point increase in BMI percentile raised the risk of infection by 9%. Participants who were overweight or obese had a 41% greater risk of infection than those who were not. More research is needed to explain these findings. In this regard, planned analyses of gene expression in cells collected from nasal swabs of participants before and after SARS-CoV-2 infection may provide clues about the inflammatory environment associated with infection, which may change as BMI increases, according to the investigators. 

The HEROS researchers found that children, teenagers and adults in the study all had around a 14% chance of SARS-CoV-2 infection during the six-month surveillance period. Infections were asymptomatic in 75% of children, 59% of teenagers and 38% of adults. In 58% of participating households where one person became infected, SARS-CoV-2 was transmitted to multiple household members.

The amount of SARS-CoV-2 found in nasal swabs, that is, the viral load, varied widely among study participants in all age groups. The viral load range among infected children was comparable to that of teenagers and adults. Given the rate of asymptomatic infection in children, a larger proportion of infected children with high viral loads may be asymptomatic compared to infected adults with high viral loads. 

The HEROS investigators concluded that young children may be very efficient SARS-CoV-2 transmitters within the household due to their high rate of asymptomatic infection, their potentially high viral loads, and their close physical interactions with family members. 

Further information about the HEROS study is available in this 2020 NIAID press release and at ClinicalTrials.gov under study identifier NCT04375761. 

Reference: MA Seibold et al. Risk factors for SARS-CoV-2 infection and transmission in households with asthmatic and allergic children. A prospective surveillance study. Journal of Allergy and Clinical Immunology DOI: 10.1016/j.jaci.2022.05.014 (2022). 

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NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website. 

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit https://www.nih.gov/. 

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JOURNAL

Journal of Allergy and Clinical Immunology

DOI

10.1016/j.jaci.2022.05.014 

https://www.eurekalert.org/news-releases/954460

Blocking influenza virus’ replication in cells

 It happens every year, especially in winter. A virus saunters into your wide-open respiratory tract, worms its way into lung cells, and, next thing you know, you’re lying in bed with a fever, aches, and chills—classic symptoms of influenza, or flu.

Research led by UC Riverside bioengineers may help stop that cycle. The team has just found a way to block one strain of the influenza virus from accessing a human protein it needs to replicate in cells. The discovery could lead to highly effective ways to treat the flu and could also apply to other respiratory viruses, such as SARS-CoV-2, which causes Covid-19.

While the flu is miserable but not life-threatening for many, it nonetheless kills tens of thousands of people each year, often the youngest and oldest members of a population. The Centers for Disease Control and Prevention estimates that flu causes 12,000 to 50,000 deaths in U.S. each year. Flu vaccines, which work by teaching the body’s immune system how to recognize and attack the virus when it enters the body, are not always effective for reasons scientists don’t yet fully understand but are likely related to the complexities of the immune system and viral mutations.

The new research, published in the journal “Viruses,” does not rely on the immune system to stop the virus. 

In order to make a person sick, the influenza virus has to infect cells in the body, where it replicates and infects more cells. Jiayu Liao, an associate professor of bioengineering at UC Riverside, previously discovered that the two most common types of flu virus, Influenza A and Influenza B, require a unique human protein to proliferate in cells and then infect more cells. 

The current work has identified a way to prevent Influenza B virus replication by blocking this necessary protein. Without the protein, virus amplification is blocked completely in cells.

The Influenza B virus uses a human cellular process called SUMOylation to modify a gene called M1, which plays multiple roles in the influenza viral life cycle. SUMOylation occurs when small ubiquitin-like modifier, or SUMO, proteins attach to and detach from other proteins to change their biochemical activities and functions. 

Liao’s experiments found that a SUMOylation inhibitor called STE025 can completely block Influenza B virus replication. The work was done with doctoral student Runrui Dang; Victor Rodgers, also a UCR professor of bioengineering; and Adolfo García-Sastre at the Icahn School of Medicine at Mount Sinai.

Influenza B virus treated with the SUMOyaltion inhibitor showed lack of SUMOylation on the M1 protein and was incapable of replicating in human cells. Influenza A also has SUMOylated proteins and could be susceptible to the SUMOyaltion inhibitor as well.

Though more work is needed for a thorough understanding of Influenza B’s dependence on SUMOylation, the finding that STE025 inhibits SUMOylation and prevents flu virus replication brings science one big step closer to making flu flee forever.

The open-access paper, “Human SUMOylation Pathway Is Critical for Influenza B Virus,” is available here

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JOURNAL

Viruses

DOI

10.3390/v14020314 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Human SUMOylation Pathway Is Critical for Influenza B Virus

ARTICLE PUBLICATION DATE

3-Feb-2022

COI STATEMENT

The A.G.-S. laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, Paratus, CureLab Oncology, CureLab Veterinary, and Pfizer, outside of the reported work. A.G.-S. is inventor of patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. All other authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

https://www.eurekalert.org/news-releases/954572

COVID-19 mortality rate five times higher among labor, retail and service workers

 A new study reveals that 68 percent of COVID-19 deaths during the first year of the pandemic were adults in low socioeconomic positions (SEP) employed in labor, service and retail jobs that require on-site attendance and prolonged close contact with others.

University of South Florida epidemiologist Jason Salemi’s research confirmed associations between COVID-19 mortality rates and socioeconomic position, gender, ethnicity and race.

In collaboration with a team of epidemiologists from the COVKID Project, Salemi, an associate professor in USF’s College of Public Health, launched a national investigation into COVID-19 deaths in 2020 with data released by the U.S. National Center for Health Statistics.

The study, published in the International Journal of Environmental Research and Public Health, analyzed nearly 70,000 adults, ages 25 to 64, who died from COVID-19.

Salemi’s research shows:

• The mortality rate of low SEP adults is five times higher when compared to high SEP adults, and the mortality rate of intermediate SEP adults is two times higher.
• White women make up the largest population group considered high SEP. In contrast, nearly 60 percent of Hispanic men are in a low SEP.
• When compared, the mortality rate of low SEP Hispanic men is 27 times higher than high SEP white women.

“The degree to which it takes a toll on communities is very unevenly distributed and we wanted to call attention to that issue,” Salemi said.

The National Center for Health Statistics uses one’s level of education as a measure of socioeconomic status because it is considered a more stable indicator of SEP over time. In tandem, the team categorized each person’s SEP by their level of education – low SEP adults had no education beyond high school, intermediate SEP had at least one year of college attendance and high SEP adults had at minimum a bachelor’s degree.

The findings reveal a person’s level of education is strongly associated with occupation segregation – with the majority of low SEP adults employed in working-class jobs across all gender, race and ethnicity groups in the United States.

Salemi and the team confirmed that hazardous conditions of work, such as working in close proximity with others, were primary drivers of disparities in COVID-19 mortality rates.

Elevated infection risks are amplified across multiple social environmental scales for working-class adults, especially when compared to high SEP workers who are more likely to have fewer exposure risks, options to work remotely, paid sick leave and better access to quality health care.

“If we were to immediately heed the calls to return to ‘normal’ and stop worrying about community spread of the virus, there are certain subsets and members of our community who are going to suffer way more so than other members – and these people have already borne the disproportionate brunt of this pandemic,” Salemi said.

As a result, Salemi says the most urgent implication of this study points to possible actions that could be considered to protect the working class from infection, such as strengthening labor laws, empowering the U.S. Occupational Safety and Health Administration, adopting safety and health hazard policies and allowing unions to organize for greater protections for worker safety.

Salemi hopes to expand on this study with mortality data from 2021 and beyond.

About the University of South Florida

The University of South Florida, a high-impact global research university dedicated to student success, generates an annual economic impact of more than $6 billion.  Over the past 10 years, no other public university in the country has risen faster in U.S. News and World Report’s national university rankings than USF. Serving more than 50,000 students on campuses in Tampa, St. Petersburg and Sarasota-Manatee, USF is designated as a Preeminent State Research University by the Florida Board of Governors, placing it in the most elite category among the state’s 12 public universities. USF has earned widespread national recognition for its success graduating under-represented minority and limited-income students at rates equal to or higher than white and higher income students. USF is a member of the American Athletic Conference. Learn more at www.usf.edu

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JOURNAL

International Journal of Environmental Research and Public Health

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Joint Effects of Socioeconomic Position, Race/Ethnicity, and Gender on COVID-19 Mortality among Working-Age Adults in the United States

ARTICLE PUBLICATION DATE

30-Apr-2022

Disclaimer: AAAS and Eurek

https://www.eurekalert.org/news-releases/954706

COVID-19 patient antibodies point researchers toward broad coronavirus vaccines

 Scientists at Scripps Research have characterized 30 antibodies that recognize a wide range of coronaviruses—successfully blocking not only all the SARS-CoV-2 variants that were tested, but other, related viruses including SARS-CoV-1, which caused the original SARS outbreak with high mortality in 2003, one found only in bats and another from pangolins. The antibodies were all isolated from people with “hybrid immunity” who had been infected with SARS-CoV-2 and subsequently vaccinated against the virus.

The new details on the antibodies, published today in Nature Immunology, are a step toward the next generation of coronavirus vaccines, which may help ward off a broader swath of viruses than the current vaccines specific to SARS-CoV-2.

“It’s very encouraging that despite SARS-CoV-2 mutating, there are still parts of the virus you can target for broad vaccination strategies,” says senior author Raiees Andrabi, PhD, an investigator in the Department of Immunology and Microbiology.

At the same time researchers work to develop new treatments and vaccines for the ongoing COVID-19 pandemic, many are also hoping to prevent the next pandemic. Coronaviruses—a broad group of viruses which also cause some common colds—have been responsible for COVID-19 as well as previous outbreaks caused by SARS-CoV-1 and Middle East Respiratory Syndrome (MERS) virus. A vaccine that helps the immune system recognize not only many SARS-CoV-2 variants, but other SARS-causing coronaviruses, could stop these viruses from spreading throughout the population.

In the new study, Andrabi and his colleagues compared antibody responses elicited in 21 people who had recovered from COVID-19, 10 people who had been vaccinated against COVID-19, and 15 with hybrid immunity from both. People with hybrid immunity showed the strongest and broadest spectrum of antibodies, able to neutralize—or block—five variants of SARS-CoV-2 (Alpha, Beta, Gamma, Delta and Omicron), SARS-CoV-1, as well as a pangolin coronavirus and one from horseshoe bats in China. No antibodies from the vaccination-only or infection-only group could neutralize all the viruses.

The team isolated 107 antibodies from two hybrid immunity donors, screening for molecules that could bind to both SARS-CoV-1 and SARS-CoV-2 spike proteins. Then, they homed in on 30 of those antibodies, many of which also neutralized the bat and pangolin coronaviruses for a closer look.

Most of those 30 antibodies, they found, recognized the same part of the viruses’ structures, called the receptor-binding domain on the spike protein. Certain segments of the receptor-binding domain, the finding suggested, were not changing as different coronaviruses evolved. The 30 antibodies also had similarities when it came to how they were produced by the body, an important clue for researchers in how to design vaccines that prompt the immune system to produce the same antibodies.

To show that the antibodies did not just bind to the viruses in the lab, but could actually impact the immune system’s ability to fight each pathogen, Andrabi’s group, in collaboration with co-senior authors Ralph Baric and Lisa Gralinski at the University of North Carolina at Chapel Hill, observed what happened when mice treated with three of the most potent antibodies—known as CC25.36, CC25.53 and CC25.54—were exposed to SARS-CoV-2, SARS-CoV-1, or the horseshoe bat virus SHC014-CoV. For all three viruses, the mice that had been treated with the antibodies had significantly lower levels of virus in their lungs compared to control mice.

“We saw amazing protection against these three viruses,” says Andrabi. “That tells us that if we are able to induce these antibodies by vaccination, they will likely give you broad protection against diverse SARS-like viruses.”

“Now that we know these antibodies work, the next goal is to design vaccines and to try to elicit similar broadly-neutralizing antibodies by vaccination in approaches that have been pioneered at Scripps Research for HIV,” says Dennis Burton, PhD, co-senior-author and chair of the Department of Immunology and Microbiology.

In addition to Andrabi, authors of the study, “Targeted isolation of diverse human protective broadly neutralizing antibodies against SARS-like viruses,” include Wan-ting He, Rami Musharrafieh, Ge Song, Katharina Dueker, Sean Callaghan, Peter Yong, Nathan Beutler, Jonathan Torres, Reid Volk, Panpan Zhou, Meng Yuan, Hejun Liu, Fabio Anzanello, Tazio Capozzola, Mara Parren, Elijah Garcia, Ian Wilson, Andrew Ward, Thomas Rogers, and Dennis Burton of Scripps Research; Long Ping Tse, David Martinez, Alexandra Schafer, Ralph Baric and Lisa Gralinski of the University of North Carolina at Chapel Hill; Stephen Rawlings and Davey Smith of University of California, San Diego; and Yana Safanova of Johns Hopkins University.

This work and the researchers involved were supported by funding from the National Institutes of Health (CHAVD UM1 AI44462 (D.R.B., I.A.W., A.D.B), the IAVI Neutralizing Antibody Center, the Bill & Melinda Gates Foundation (INV-004923), the Translational Virology Core of the San Diego Center for AIDS Research (CFAR) grant (NIH AI036214, 5T32AI007384, AI149644, AI157155, and R21 AI145372), the John and Mary Tu Foundation,  the James B. Pendleton Charitable Trust, a Pfizer NCBiotech Distinguished Postdoctoral Fellowship in Gene Therapy, a Burroughs Wellcome Fund Postdoctoral Enrichment Program Award and a Hanna H. Gray Fellowship from the Howard Hughes Medical Institute.

About Scripps Research

Scripps Research is an independent, nonprofit biomedical institute ranked the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more at www.scripps.edu.

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JOURNAL

Nature Immunology

https://www.eurekalert.org/news-releases/954792

CDC treats first monkeypox patient with SIGA's smallpox antiviral via expanded access

 The CDC said Friday that one monkeypox patient in the US so far has been treated with SIGA Technologies’ tecovirimat, known commercially as TPOXX, which is an antiviral agent from the strategic national stockpile with anti-orthopoxvirus activity.

The antiviral is only currently licensed to treat smallpox, so the FDA and company made it available to CDC under an expanded access IND.

CDC also said it released smallpox vaccines — Emergent’s ACAM2000 and Bavarian Nordic’s Jynneos — to those at high-risk of exposure to monkeypox, either through contact with someone who has it, or certain intermediate risk exposures, such as being within ≤6 feet of an unmasked patient for ≥3 hours without wearing, at a minimum, a surgical mask.

But the CDC also warned that the post-exposure prophylaxis of the vaccine is not recommended for those at low or uncertain risk of monkeypox (“e.g., health care providers entering a patient’s room without eye protection”).

News of the first use of treatment and vaccines comes as the CDC says the outbreak of monkeypox, a zoonotic disease from a so-far unknown animal reservoir, is now in 9 states. As of May 31, the CDC has identified 17 cases in the US, with 16 cases diagnosed in persons who identify as gay, bisexual, or men who have sex with men. Fourteen of the 17 patients also reported international travel involving 11 different countries during the 21 days preceding symptom onset.

“Currently, all patients are clinically well and being monitored by health authorities to determine the end of isolation (i.e., after all lesion scabs have fallen off, and new, healed skin has formed),” the agency said.

But CDC’s contact investigation is ongoing, as among the 13 patients who have identified contacts, there are 56 high-, 117 intermediate-, and 235 low- or uncertain-risk contacts.

“Contacts are recommended to be monitored for signs and symptoms consistent with monkeypox (e.g., fever, chills, lymphadenopathy, and rash) for 21 days following last exposure,” the CDC said in a report issued Friday.

While the virus is endemic in several central and West African countries, the CDC said there are two clades of monkeypox virus, West African and Congo Basin, the latter causing more severe illness. Since monkeypox reemerged in Nigeria in 2017, isolated cases have occurred outside Africa but they have been either people recently traveling to Nigeria or contacts of persons with travel-associated cases.

The UK, which is seeing its own surge of monkeypox cases too, is planning to commission a Phase 2 study to investigate the efficacy of tecoviramat for the management of monkeypox in a non-hospitalized population.

https://endpts.com/cdc-treats-first-monkeypox-patient-with-sigas-smallpox-antiviral-via-expanded-access/

Can wearables help Parkinson's patients? Verily publishes new data

 It may be soon that wearables can be used for more than just receiving texts or measuring your steps.

Building on previous research showing sensors can be used to monitor symptoms, Verily, Alphabet, Inc.’s research organization, posted a paper detailing a new smartwatch-based virtual exam for patients with Parkinson’s.

The study, which started in 2020 and enrolled 370 participants, examined patients weekly as they performed various motor tasks both in-clinic and remotely. The wearable also allowed users to input when they took their medication.

At week 1, around 80% of patients had completed at least one motor exam. During week 52, 40% did at least one exam.

Researchers were able to develop reliable digital measures for Parkinson’s symptoms like upper-extremity bradykinesia and rest tremors. The study also measured gait impairment, and while researchers found that arm swing acceleration was not the best outcome measure, it did show solid performance, the researchers said.

According to the paper, the results are on par with similar published analyses of wrist-worn sensors, and while this study can demonstrate the ability of a wearable to provide metrics that map the observations of an expert clinician, more studies are necessary to determine their full potential.

“The system allows for an increased frequency of data collection, enabling monthly aggregation of measurements, leading to increased test-retest reliability. In turn, high reliability suggests that these measures have potential as digital biomarkers of progression. Further research is needed to more firmly establish the ability of these and other measures to serve as progression biomarkers,” the paper said.

Alphabet is not the only company looking into using wearables to assist Parkinson’s patients. In 2021, researchers at Silicon Valley giant Apple designed a system that can enable the Apple Watch to detect the motor symptoms that are a major calling card of the disease. The results of their work were posted in the journal Science Translational Medicine.

While tech companies keep up on the monitoring side, pharma is continuing its fight against the disease, which is one of the hardest to treat. In May, AbbVie approached the FDA with a new therapy to potentially treat the disease using prodrugs of two medications commonly used for the condition.

https://endpts.com/can-wearables-help-parkinsons-patients-verily-publishes-new-data-from-virtual-exams/

Orphan drugs’ financial success raises questions

 R&D into orphan drugs is growing alongside the number of approved treatments, providing treatments for rare diseases that previously did not have any. However, Ben Hargreaves finds that the blockbuster success that certain treatments are achieving is beginning to raise questions over whether healthcare systems can afford this in the long-term.

In 1983, the US Congress passed the Orphan Drug Act to encourage more pharmaceutical companies to engage in R&D to develop treatments for rare diseases through the offering of financial incentives. The Act worked; prior to its passage, there were only 10 drugs approved to treat rare diseases in the US, following this period there were a total of 5,099 treatments that received orphan drug designation and 838 approvals, as of 2019.

As covered in a previous article, the importance of R&D to develop treatments for rare diseases is high. There are approximately 7,000 rare diseases and only 5% of these have an effective treatment. It is estimated that between 3.5 to 5.9% of the global population are affected by a rare disease. This is why the action by the US in 1983 and subsequently the European Commission Regulation No. 141/2000 (the Orphan Regulation), that both acted to encourage development in the area, are regarded as crucial for changing the landscape in rare disease R&D.

The price is right

Evaluate Pharma’s recent Orphan Drug Report subtitled its overview of the market ‘Niche no longer.’ This is based on the relative success orphan drugs have achieved, in terms of the number of approvals and the sales figures achieved for this area. By 2026, the report predicts that each of the top 10 selling orphan drugs will earn between $3 billion and $13 billion. While in 2021, orphan drugs made up over half of all the US FDA’s approvals, with the figures in European being similarly high – 19 out of 54 approved new active substances.

The report estimates that the orphan drug market will grow twice as fast as the non-orphan market, with a 2021 to 2026 compound annual growth rate of 12%. By 2026, this would mean that orphan drug sales will account for 20% of all prescription drug sales. Evaluate expects five big pharma companies to be reliant on orphan drugs to provide 20% or more of their sales by 2026, with Johnson & Johnson topping the list at an estimated 39% of all sales.

When asked by pharmaphorum why product sales are expected to be so high in this area, a spokesperson for Evaluate explained: “For many rare diseases, there is high unmet need which results in high levels of use of orphan products in the eligible patient groups, and these groups are often larger than anticipated once treatments become available. And of course, in many cases, these drugs have higher than average price tags compared to the wider market which is due to the limited – or in most cases – non-existent competition within a treatment area.”

Raising questions

As a result of these factors, there are now questions beginning to be asked over whether the financial incentives provided to the development of orphan drugs are suited to the current landscape. A recent ICER report stated that “This unmet need is an enduring part of the orphan disease landscape, but it is now shadowed by a problem not foreseen by the authors of the Orphan Drug Act. The rapid growth in approved rare disease treatments in recent years has created concerns about the pricing of orphan drugs and their cumulative affordability to the health system.”

To provide evidence for this assertion, ICER cited that the average annual cost of an orphan treatment per patient was $32,000 in the US, with treatment cost ranging from $6,000 to $500,000 per year. According to the organisation, 39% of orphan drugs cost more than $100,000 annually. Beyond this, ICER highlighted that orphan drugs “are commonly approved with more limited evidence on relative safety and effectiveness due to their reliance on non-randomized trials using short-term surrogate outcomes.”

The question of how to effectively pay for these treatments has now reached the point where it is being discussed at the highest levels in the US and Europe. Last year, the European Commission launched an open public consultation on the revision of the legislation to identify shortcoming in the system. While in the US, Congress has proposed limits to the Orphan Drug Tax Credit, as part of the Build Back Better Act.

A spokesperson for the European Federation of Pharmaceutical Industries and Associations (EFPIA) told pharmaphorum that the revision to legislation in Europe is an opportunity to ‘drive more research’ into researching new medicines. They added, “Existing incentives and rewards remain essential, as the economic case for investment in these areas is only marginal.”

Reaching a compromise

The broader movement across the industry is towards managing the financial cost of treatments. This can be seen with the debate in the US over the price of insulin, with the cost of drugs becoming a wider political issue in the US. While Evaluate’s report identified Germany’s drug cost-watching, IDWiG, as also calling for a review of the cost of orphan drugs. However, the spokesperson for Evaluate does not see any sign of immediate action in Europe in the area of orphan drugs. They stated that “we don’t have any sense of timelines on this, but it’s unlikely to be imminent.”

Regardless of whether action will be immediate or not, the spokesperson indicated that the likeliest action that the pharma industry will take is to engage in negotiations. They added that this could see companies pursue ‘outcomes-based agreements’, where price and reimbursement is tied to evidence of benefit. This kind of approach has already been considered when the first CAR-T treatments were launched due to the high cost of the treatment, which arrived on the US market at $475,000.

The spokesperson for the EFPIA warned that at the current pace of drug development in the rare disease space, it will take over 100 years to develop treatments for all known rare conditions. Rather than focusing on cost, the spokesperson said that “We need to join forces and share a ‘moonshot’ mindset to get a deeper understanding of diseases, develop basic science and accelerate translational research, for example by setting up Europe-wide patient registries.”

https://pharmaphorum.com/market-access-2/orphan-drugs-financial-success-raises-questions/