The US imports a large share of antibiotics and antibiotic active ingredients from China and India, but import prices fell dramatically

Food for thought! Is this international division of labor acceptable! How large is the risk of dependency or the supply chain vulnerabilities?

"The U.S. has become increasingly reliant on other countries for antibiotics over the past several decades, per a new analysis by Johns Hopkins University researchers that shows that China supplies more than 60% of the active pharmaceutical ingredients U.S. antibiotics manufacturers need—and, since 2020, nearly a third of the finished antibiotics imported by the U.S. come from India. CIDRAP "

"... The authors of the study say the findings suggest the United States, which already faces persistent drug shortages and is no longer able to domestically produce key antibiotics such as penicillin and doxycycline, is becoming overdependent on other countries for its antibiotic supply and highly vulnerable to supply chain disruptions that could affect public health. ..."

From the key points and abstract:

"Key Points

Question

Where do antibiotics for the US market come from?

Findings

This cross-sectional study analyzed 1992 to 2024 antibiotic importation records and found 50 originating countries of finished dosage forms and 52 countries for active pharmaceutical ingredients as well as a significant increase in annual antibiotic imports and a decrease in importation prices. In the past 5 years, India was the leading originating country for finished dosage forms, with China as the leading originating country for antibiotic active pharmaceutical ingredients.

Meaning

US relies on diversified global sources for antibiotic drugs but primarily on China for antibiotic active ingredients; policies to strengthen domestic production and diversify sourcing are critical to mitigate supply chain vulnerabilities.

Abstract

Importance  The US has faced persistent antibiotic shortages over the past decade, compromising patient care, public health, and national security. Understanding the global sources of US antibiotic imports is critical to inform policies to improve supply chain resilience.

Objective

To identify the global sources of US antibiotic imports, focusing on finished dosage forms (FDFs) and active pharmaceutical ingredients (APIs) between 1992 and 2024.

Design and Setting

This cross-sectional study of US antibiotic importation records used data from USA Trade Online from January 1992 to July 2024. Data included import volumes, costs, and the originating country.

Main Outcomes and Measures

Trends in annual import volumes for antibiotic FDFs and APIs (metric tons), spending and price per kilogram (inflation-adjusted dollars), and market concentration measured by the Herfindahl-Hirschman Index (HHI). An HHI less than 1500 indicates an unconcentrated (ie, competitive) market, 1500 to 2500 indicates a moderate concentration, and greater than 2500 indicates high concentration.

Results 

The final sample included 50 FDF-originating countries and 52 API-originating countries. Compared with the annual volume of US antibiotic FDF imports in 1992, the annual volume in 2024 increased 2595.0%, while the annual volume of API imports remained relatively stable.

Mean inflation-adjusted importation prices for FDFs decreased from $1836.03 per kg in 1992 to $177.44 per kg in 2024.

For APIs, mean prices decreased from $351.74 per kg in 2003 to $65.69 per kilogram in 2024.

From 2020 to 2024, India was the leading originating country for FDFs (31.9% of the total imported volume and 18.2% of the total imported cost), followed by Italy (13.4% of the total volume and 22.4% of the total cost).

China was the leading originating country for APIs (62.6% of the total imported volume and 28.7% of the total cost), followed by Bulgaria (16.1% of the total volume and 3.8% of the total cost). Italy was the originating country for 2.6% of API imported volume but accounted for 27.9% of the importation costs.

HHI revealed that FDF importation has become unconcentrated since 2020 (HHI, 1500-2500), while API importation markets are highly concentrated (2024 HHI, >5000).

Conclusions and Relevance

This study found that US antibiotic importation relies on diversified global sources for FDFs but primarily on China for APIs. Policies to strengthen domestic production and diversify sourcing are critical to mitigate supply chain vulnerabilities. Improved traceability and targeted strategies for specific antibiotics are recommended to safeguard public health and national security."

Global Health NOW: Tobacco Use Falls, Industry Pivots; Aid Cuts Hit Yemen Amid Measles Crisis; and Conversion Therapy Goes Before the Court

US relies heavily on China, other nations for antibiotics

US Antibiotic Importation and Supply Chain Vulnerabilities (open access)

Figure 1.  Trends in Annual Antibiotic Importation Volume, Spending, and Price, 1992 to 2024

Figure 2.  Annual Antibiotic Finished Dosage Form (FDF) and Active Pharmaceutical Ingredient (API) Importation Volume by Originating Country From 1992 to 2024

10 patients With Severe Diabetes Are Cured in Small clinical Trial of a New Drug

Good news! This could be a breakthrough!

Two deaths occurred among the 14 selected patients, but these death were apparently unrelated to the treatment.

"A single infusion of a stem cell-based treatment may have cured 10 out of 12 people with the most severe form of type 1 diabetes. One year later, these 10 patients no longer need insulin. The other two patients need much lower doses.

The experimental treatment, called zimislecel and made by Vertex Pharmaceuticals of Boston, involves stem cells that scientists prodded to turn into pancreatic islet cells, which regulate blood glucose levels. The new islet cells were infused and reached the liver, where they took up residence. ..."

"... – All 12 patients with at least one year of follow-up who received a full dose of zimislecel as a single infusion achieved ADA-recommended target HbA1c levels <7% and >70% time-in-range (70-180 mg/dL), and 10/12 patients were insulin free – ..."

From the abstract:

"Background

Zimislecel is an allogeneic stem cell–derived islet-cell therapy. Data on the safety and efficacy of zimislecel in persons with type 1 diabetes are needed.

Methods

We conducted a phase 1–2 study of zimislecel in persons with type 1 diabetes.

In part A, participants received a half dose of zimislecel (0.4×109 cells) as a single infusion into the portal vein, with an option for a second half dose within 2 years. In parts B and C, participants received a full dose of zimislecel (0.8×109 cells) as a single infusion.

All the participants also received glucocorticoid-free immunosuppressive therapy.

The primary end point in part A was safety. The primary end point in part C was freedom from severe hypoglycemic events during days 90 through 365, with a glycated hemoglobin level of less than 7% or a decrease of at least 1 percentage point from baseline in the glycated hemoglobin level at one or more time points between days 180 and 365.

Secondary end points in part C included safety and insulin independence between days 180 and 365.

Assessment of the primary and secondary end points in part C involved the participants who received the full dose of zimislecel as a single infusion in part B or C. 

Detection of serum C-peptide during a 4-hour mixed-meal tolerance test was used to assess engraftment and islet function. All the analyses were interim and not prespecified.

Results

A total of 14 participants (2 in part A and 12 in parts B and C) completed at least 12 months of follow-up and were included in the analyses.

C-peptide was undetectable at baseline in all 14 participants.

After zimislecel infusion, all the participants had engraftment and islet function, as evidenced by the detection of C-peptide.

Neutropenia was the most common serious adverse event, occurring in 3 participants.

Two deaths occurred — one caused by cryptococcal meningitis and one by severe dementia with agitation owing to the progression of preexisting neurocognitive impairment.

All 12 participants in parts B and C were free of severe hypoglycemic events and had a glycated hemoglobin level of less than 7%; these participants spent more than 70% of the time in the target glucose range (70 to 180 mg per deciliter).

Ten of the 12 participants (83%) had insulin independence and were not using exogenous insulin at day 365.

Conclusions

The results of this small, short-term study involving persons with type 1 diabetes support the hypothesis that zimislecel can restore physiologic islet function, warranting further clinical investigation. ..."

People With Severe Diabetes Are Cured in Small Trial of New Drug - The New York Times

Vertex Presents Positive Data for Zimislecel in Type 1 Diabetes at the American Diabetes Association 85th Scientific Sessions (original news release)

Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes (no public access)

LSD analogue synthesised by swapping just two atoms less likely to cause hallucinations and it exhibited strong neuroplastic effects

Good news! Amazing stuff! Flipping just two atoms!

"An analogue of the psychedelic drug LSD has been found to offer the same therapeutic effects as LSD but is less likely to cause the hallucinogenic trips associated with the drug. The researchers say that their work highlights the potential of rationally designed, non-hallucinogenic psychedelic analogues in the treatment of neuropsychiatric diseases such as schizophrenia, where the use of psychedelics is not recommended. ...

Using tests, such as the mouse head twitch response assay, which, ... correlates well with human hallucinogenic potency, they found that JRT did not produce hallucinogenic-like behaviours in mice dosed with LSD. ... in contrast to LSD, JRT does not bind the 5-HT2A receptor for very long. ..."

"... researchers have developed a new, neuroplasticity-promoting drug closely related to LSD that harnesses the psychedelic’s therapeutic power with reduced hallucinogenic potential. ..."

To design the drug, dubbed JRT, researchers flipped the position of just two atoms in LSD’s molecular structure. The chemical flip reduced JRT’s hallucinogenic potential while maintaining its neurotherapeutic properties, including its ability to spur neuronal growth and repair damaged neuronal connections that are often observed in the brains of those with neuropsychiatric and neurodegenerative diseases. ...

JRT exhibited powerful neuroplastic effects and improved measures in mice relevant to the negative and cognitive symptoms of schizophrenia, without exacerbating behaviors and gene expression associated with psychosis. ..."

From the significance and abstract:

"Significance

Psychedelic compounds, such as lysergic acid diethylamide (LSD), can promote the growth of atrophied cortical neurons, which is relevant to the treatment of numerous brain conditions.

However, their hallucinogenic properties have limited their adoption as medicines and preclude their use in certain patient populations, such as those with schizophrenia or a family history of psychosis.

By transposing only two atoms, we have created JRT, an exceptionally potent analogue of LSD with lower hallucinogenic potential, improved pharmacological selectivity, and the ability to produce a wide range of therapeutic effects.

Our work highlights the potential of rationally designed, nonhallucinogenic analogues of psychedelics for treating diseases where the use of psychedelics is contraindicated.

Abstract

Decreased dendritic spine density in the cortex is a key pathological feature of neuropsychiatric diseases including depression, addiction, and schizophrenia (SCZ).

Psychedelics possess a remarkable ability to promote cortical neuron growth and increase spine density; however, these compounds are contraindicated for patients with SCZ or a family history of psychosis.

Here, we report the molecular design and de novo total synthesis of (+)-JRT, a structural analogue of lysergic acid diethylamide (LSD) with lower hallucinogenic potential and potent neuroplasticity-promoting properties.

In addition to promoting spinogenesis in the cortex, (+)-JRT produces therapeutic effects in behavioral assays relevant to depression and cognition without exacerbating behavioral and gene expression signatures relevant to psychosis.

This work underscores the potential of nonhallucinogenic psychoplastogens for treating diseases where the use of psychedelics presents significant safety concerns."

LSD analogue synthesised by swapping just two atoms less likely to cause hallucinations | Research | Chemistry World

Researchers Develop an LSD Analogue with Potential for Treating Schizophrenia (original news release)

Molecular design of a therapeutic LSD analogue with reduced hallucinogenic potential (open access)

JRT differs from LSD in the positioning of two atoms. An N and C in the ergoline structure of LSD have been swapped to make the less hallucinogenic JRT

Fig. 2 Total synthesis of JRT.