Jared Kaltwasser

The US Food and Drug Administration (FDA) has accepted an investigational new drug application for an oral prophylactic candidate designed to prevent transmission of Lyme disease.

, announced the acceptance last week. The company said it will now proceed with a Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of the pill, which it has named TP-05.

“Currently, there are no approved pharmacological prophylactic options for tick kill and preventing transmission of Lyme disease, which has the potential to cause severe, often debilitating symptoms with permanent and irreversible damage, said Bobak Azamian, MD, PhD, the company’s president and CEO.

The company said about 300,000 people in the US are infected with Lyme disease each year, but another 30 million people are believed to be at high or moderate risk of contracting the disease.

Lyme disease is transmitted through the bites of blacklegged ticks who are infected with the 

 bacteria. People who spend extended periods of time outdoors, especially in wooded areas, are at highest risk, since those are areas where ticks are most common.

. Rather, it is an oral systemic formulation of lotilaner. Other formulations of the drug have been used successfully to control fleas and ticks in household pets. The drug paralyzes and kills parasites by inhibiting parasite-specific GABA-Cl channels before the ticks can transmit 

TP-05 is designed to be taken before a person is bitten by a tick. If it successfully navigates the clinical trial process, the pill could be taken by people as a proactive measure prior to spending time outdoors or in areas where Lyme disease is endemic, the company said.

Tarsus added that prevention is particularly beneficial with a disease like Lyme disease, because many people do not notice that they have been bitten by a tick until the tick has already transmitted Lyme disease.

The phase 1 study, which is expected to launch this July, will be a single ascending dose and multiple ascending dose (SAD/MAD) study, the company said. Tarsus is also exploring the possible use of TP-05 to stop transmission of malaria, another common parasitic infection.

Tarsus is also in the midst of a pivotal trial evaluating the safety and efficacy of TP-03, a topical ophthalmic formulation of lotilaner, for the treatment of Demodex blepharitis, the company said. That condition is caused by Dermodex mites.

Azamian noted that Lyme disease is associated with symptoms such as inflammation, nerve, joint, and muscle pain, among other symptoms. More severe cases can result in neurological complications, including facial palsy, meningitis symptoms, and severe headaches. Patients who go 

 or months are at a higher risk of treatment failure and more severe symptoms.

“There is a significant unmet need for a therapeutic to quickly and reliably prevent this disease that can lead to poor outcomes for so many people,” he said, in the press release. “We look forward to initiating our clinical development program for TP-05 and advancing the path for this much-needed therapeutic for Lyme disease prevention.”

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About 300,000 people get Lyme disease each year. A new investigational prophylactic could provide people in high-risk settings with an opportunity to prevent infection.

Company Gets Go-Ahead to Study Prophylactic Pill for Lyme Disease

A new study of patients with mild COVID-19 symptoms suggests treatment with the inhaled glucocorticoid budesonide (Pulmicort) can reduce the likelihood of hospitalization and shorten recovery periods.

, could lead to improved, easily accessible care for patients at risk of severe COVID-19 disease.

Corresponding author Mona Bafadhel, MBChD, PhD, of the University of Oxford, and colleagues, began their study after noticing that patients with chronic respiratory disease seemed to be under-represented in the 

“We hypothesized that this under-representation might be due to the widespread use of inhaled glucocorticoids in these patients,” Bafadhel and colleagues wrote.

In addition, the authors noted that most of the time, 

 are used by patients with asthma and chronic obstructive pulmonary disease (COPD) to reduce exacerbations, and those exacerbations are believed to be the result of viruses. Thus, they wondered, perhaps the drugs’ effectiveness in treating regular symptom exacerbations might translate to effectiveness against the SARS-CoV-2 virus.

The authors recruited 167 patients during the last half of 2020, each of whom had mild COVID-19 with symptoms beginning no more than 7 days prior to enrollment. Patients were randomly assigned to one of 2 groups: one received usual care, and the other received treatment with inhaled budesonide at a dose of 400 μg per actuation, administered via turbohaler. Patients were asked to take two inhalations twice per day until symptoms went away. The primary endpoint was COVID-19-related hospital admissions or emergency room visits. The secondary endpoint was patient-reported measures of symptoms. The analyses were run for both the per-protocol and intention-to-treat (ITT) populations.

A total of 139 patients were included in the per-protocol analysis. Among the 70 patients in the standard-care group, 10 (14%) received COVID-19 related urgent care. Of the 69 patients in the budesonide group, just 1 patient required emergency care.

Similarly, in the ITT population, 11 patients (15%) in the usual-care group sought emergency care, compared to 2 patients (3%) in the budesonide group. The number of patients needed to be treated with budesonide to reduce COVID-19 deterioration was 8.

Patients with budesonide had quicker resolution of symptoms compared to the usual-care group (8 days versus 7 days), and they also had fewer days with fever.

Bafadhel and colleagues said the therapy’s ability to lessen COVID-19 severity was significant.

“This effect, with a relative reduction of 91% of clinical deterioration is equivalent to the efficacy seen after the use of COVID-19 vaccines and greater than that reported in any treatments used in hospitalized patients with severe COVID-19,” they said.

Since their study had broad inclusion criteria, including patients with comorbidities and a median age in the mid-40s, the authors said their findings could be important for public health agencies around the world, especially in countries with fewer resources.

“In addition, in high-income countries, inhaled budesonide could work as an adjunct to reduce pressure on healthcare systems until widespread SARS-CoV-2 vaccination can be achieved,” they said.

The investigators said their findings will need to be validated, but they said such validation needs to take place quickly in order to maximize the impact of the potential new therapeutic option.

Patients who received the inhaled glucocorticoid budesonide in the first several days of COVID-19 symptoms were much less likely to require hospital care.

Inhaled Glucocorticoids Could Ease COVID-19 Symptoms

Transgender women are being infected with HIV at high rates and are in urgent need of HIV prevention and treatment services, according to a new report from the US Centers for Disease Control and Prevention (CDC).

 is based on a survey of 1,608 transgender women living in 7 major US cities: Atlanta, Los Angeles, New Orleans, New York City, Philadelphia, San Francisco, and Seattle. The CDC found 4 in 10 of the respondents (42.2%) were infected with HIV. The rate was even higher among 

, with 61.9% of respondents HIV-positive. Eleven of the 17 American Indian/Alaska Natives surveyed were HIV positive, though they also represented the smallest sample size within the racial and ethnic breakdown in the report. White transgender women had the lowest rate of HIV positivity, at just 17%.

One reason for the high rates, according to Demetre Daskalakis, MD, MPH, director of the CDC’s Division of HIV/AIDS Prevention, is that nearly two-thirds of the women in the study were living at or below the federal poverty level, and 42% had been homeless at some point in the 12 months prior to the study, which was conducted in 2019 through early 2020.

“These data provide a clear and compelling picture of the severe toll of HIV among transgender women and the social and economic factors – including systemic racism and transphobia – that are contributing to this unacceptable burden,” Daskalakis said,.

Those high rates of HIV exist despite the fact that pre-exposure prophylaxis (PrEP) can dramatically reduce the risk of contracting HIV, and patients with HIV can use antiretroviral therapy to suppress viral loads to undetectable levels.

Yet, the CDC report makes clear that such interventions are not making it to all populations.

Only 32% of respondents in the survey who were HIV-negative reported using PrEP. One possible reason is that they fear drug interactions between gender-affirming hormone treatments and PrEP, the report said. The study found two-thirds of participants without HIV were taking such hormones. Other potential factors include mistrust of medical professionals due to experiences of transphobia and a lack of trans-inclusive marketing.

Daskalakis said public health agencies need to do more to directly reach the transgender community.

“Reducing HIV in these communities will require that public health and other providers of social and 

 design innovative and comprehensive status-neutral solutions to overcome barriers to whole person prevention and care,” Daskalakis said.

Notably, while use of PrEP was low, a majority of transgender women who contracted HIV said they are receiving healthcare post-infection. Nearly all of the respondents (95%) said they had visited a healthcare provider for HIV, and 63% said that visit came within one month of diagnosis, and 89% saying they saw a provider within six months of their survey interview. Fully 90% of HIV-positive transgender women in the survey said they were using antiretroviral therapy.

The CDC has set a goal of reducing new HIV infections by 90% by 2030 as part of its 

. The CDC also said it will spend nearly $11 million per year in a 5-year program to fund community-based organizations’ efforts to facilitate HIV testing, care linkage, and prevention services among the transgender population

The new report highlights the broad disparities in HIV health among different populations, with Black transgender women facing the highest rates of HIV infection.

CDC: 42% of Transgender Women in Select US Cities Are HIV Positive

The number of deaths in the United States rose sharply last year, reaching levels that cannot be fully explained by the official count of coronavirus disease 2019 (COVID-19) deaths, according to a new analysis.

Journal of the American Medical Association

covers the period between March 1, 2020 and Jan. 2, 2021. It is based on data from the National Center for Health Statistics and the US Census Bureau. The data cover 49 states and the District of Columbia. North Carolina was not included due to insufficient data, the report’s authors said.

During that time frame covered by the analysis, a total of 2,801,439 deaths from all causes were reported in the US. That’s 22.9% higher (522,368 deaths) than would have been expected in a normal year.

according to the US Centers for Disease Control and Prevention (CDC)

, the total number of people dying from COVID-19 in the calendar year 2020 was approximately 375,000.

Corresponding author Steven H. Woolf, MD, MPH, of the Center on Society and Health at Virginia Commonwealth School of Medicine, and colleagues, explained that some of those excess deaths not reflected in the CDC count 

might still have been related to the pandemic

“Excess deaths not attributed to COVID-19 could reflect either immediate or delayed mortality from undocumented COVID-19 infection, or non–COVID-19 deaths secondary to the pandemic, such as from delayed care or behavioral health crises,” they said. “Death rates from several non–COVID-19 diseases (eg, heart disease, Alzheimer disease) increased during surges.”

, which found that between March and July 2020, the number of actual US deaths was 20% higher than would be expected in a normal year. The similarity in the excess mortality rate suggests that, even as hospitals around the world got better at identifying and treating COVID-19, surges in cases and downstream effects on the healthcare system remained problematic.

“While we made progress in treating COVID-19, there was an extraordinary number of deaths in the summer surge and particularly during the early winter holiday period,” Woolf told 

 “This contributed greatly to the large increase in excess deaths for the year. And sadly, so many of these deaths were preventable.”

The investigators also found significant variance between regions. For instance, New York State had the largest relative increase in all-cause mortality, with a 38.1% increase. However, the other states populating the top 10 states in terms of excess deaths were mostly in the midwest (South Dakota, North Dakota and Ohio) and southeast (Alabama, Louisiana, and Mississippi). Woolf and colleagues noted that many of those states “weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states.”

. For instance, while non-Hispanic Blacks make up just 12.5% of the US population, they made up 16.9% of the excess deaths reported in the study. That data point aligns with other reports suggesting racial minorities have been hit harder by the pandemic, compared to other groups.

Woolf and colleagues noted that their data have some limitations. For instance, the report is based in part on provisional data and could also be affected by inaccurate death certificates. Such limitations, though, are part of the reason it’s important to look at excess all-cause mortality, rather than focusing simply on deaths directly linked to COVID-19.

“We need programs like [Johns Hopkins University’s] COVID Tracking Project to keep the nation informed of the number of deaths attributed to the virus, as well as case numbers and hospitalizations,” he said. “But we also need to monitor excess deaths, a measure that is agnostic about the vagaries of cause of death attribution and gives the nation a fuller sense of the death toll a crisis brings. This is true not only for pandemics but also for other natural disasters, such as earthquakes, hurricanes, etc.”

Overall, more than half a million more people died between March 2020 and the end of the year, suggesting the pandemic may have been indirectly involved in more deaths than previously realized.