There are about 2.3 million new cases of breast cancer and 700,000 deaths every year, and approximately 80% of patients with primary breast cancer are able to be cured if diagnosed and treated promptly. In many cases, according to the investigators, the cancer has already spread to other parts of the body at the time of diagnosis. Metastatic cancer is often incurable and makes up over 90% of deaths related to cancer.

Because there are no in vitro models to study how breast cancer can spread to secondary organs, including bone, lungs, liver, or brain. For this study, the investigators created a novel model that uses invasion/chemotaxis (IC)- and extravasation (EX)-chip platforms to model a bone-like cellular microenvironment that consists of cell lines that represent osteoblasts, stromal cells, and monocytes embedded in 3D collagen I-based extracellular matrices.

The IC- and EX-chips allowed the investigators to visualize and quantify the invasion and extravasation potentials of metastatic breast cancer cell line MDA-MB-231 toward lung, liver, and breast microenvironments. The investigators also tested the platforms with MDA-MB-231 clones LM2 and BoM 1833, which specifically metastasize to lung and bone, respectively, in mouse models.

The study authors demonstrate that the invasion and extravasation potentials of the MDA-MB-231 clones toward the microenvironment on IC- and EX-chips correlate with their in vivo behaviors, and these platforms allow a straightforward approach to providing in vitro data representative of in vivo bone metastasis risk for breast cancer cell lines. The investigators note that if further improvements to the tested platforms are made, they can allow for the analysis of clinical samples and develop site-specific clinical approaches.

“Breast cancer most frequently spreads to bone, with an estimated rate of 53%, resulting in severe symptoms such as pain, pathological bone fractures, and spinal cord compressions. Our research provides a laboratory model that estimates the likelihood and mechanism of bone metastasis occurring within a living organism. This advances the understanding of molecular mechanisms in breast cancer bone metastasis and provides the groundwork for developing preclinical tools for predicting bone metastasis risk,” Burcu Firatligil-Yildirir, postdoctoral researcher at Tampere University, said in a news release.

In addition to the correlations found between the behaviors of the MDA-MB-23 breast cancer cells on the chip models and their in vivo potential, the culture model also shows that collagen I can offer a better bone-like environment of bone cells and matrix composition, and stiffness regulate the invasion of breast cancer cells. According to the authors, using in situ contactless rheological measurements under cell culture conditions showed a presence of cells that increased the stiffness values for matrices up to 1200 Pa after being monitored for 5 days. This suggests that the cellular composition has a significant effect on the regulation of matrix mechanical properties, which can contribute to the invasiveness.
 

According to the investigators, the evaluated platforms can allow for the investigation of underlying molecular mechanisms that are present in breast cancer bone metastasis, therefore, providing groundwork to develop preclinical tools to predict the risk of bone metastasis. Additionally, they note that developing sustainable in vitro models that mimic the native breast and bone microenvironments’ complex natures is a multidisciplinary challenge.

“Our work shows that physiologically relevant in vitro models can be generated by combining cancer biology, microfluidics and soft materials. The results open new possibilities for developing predictive disease, diagnostic and treatment models,” Nonappa, associate professor and leader of the Precision Nanomaterials Group at Tampere University, said in the news release.

REFERENCES

1. Tampere University. Study shows why breast cancer spreads to bone. News release. October 18, 2024. Accessed October 30, 2024. https://www.eurekalert.org/news-releases/1061808

2. Firatligil-Yildirir B, Bati-Ayaz G, Nonappa, Pesen-Okvur D, Yalcin-Ozuysal O. Invasion/chemotaxis- and extravasation-chip models for breast cancer bone metastasis. PLoS ONE. 2024;19(10):e0309285 doi:10.1371/journal.pone.0309285

The US Preventive Services Task Force (USPSTF) current guidelines recommend adults aged 50 to 80 years who have a 20 pack-year smoking history, currently smoke, or have quit within the past 15 years to receive an annual screening for lung cancer with LDCT. The screenings can be completed once the individuals reaches 15 years smoke-free or develops a health issue that limits life expectancy or the ability to have curative lung surgery, according to the release.
 However, data from the American Lung Association (ALA) found that only 4.5% of LCS eligible individuals were up to date on screenings.

The study used data for individuals aged 50 to 80 years from the 2022 Health Information National Trends Survey (HINTS)-6, conducted by the US National Cancer Institute. Individuals in the survey were asked to self-report their smoking status, sociodemographic, and clinical information. A total of 929 individuals who formerly smoked and 350 individuals who currently smoke were identified and included. Individuals with a smoking status were asked, “at any time in the past year, did a doctor or other health professional talk with you about having LDCT scan to check for lung cancer?” Individuals that responded, “I have never heard of this test” and “no”, were analyzed by smoking status, according to study authors.

The study authors noted that results showed that among the 929 individuals who formally smoked, 18.1% had never heard of LCS and 75.1% never discussed LCS with their health care provider. Among the 350 individuals that currently smoked, 13.5% had never heard of LCS and 71.1% did not discuss it with their health care provider.

In total, more than 80% of individuals in both smoking groups have neither heard of LCS nor discussed a screening with a clinician, regardless of their sex, race, ethnicity, educational attainment, household income, urbanicity vs rurality, health insurance status, and unmet social determinants. Additionally, more than 60% of individuals with a history of cancer or comorbid cancer did not discuss LCS with their health care providers, according to the release.

The findings suggest that less than 16% of high-risk lung cancer individuals have heard or discussed LCS with a health care provider and displayed a lack of advocacy for LCS across all sociodemographic and clinical subgroups.

“These findings are troubling because 13.1 million individuals meet the LCS eligibility criteria (ie, 20 pack-years and <15 years since quitting).Our data emphasize the need for increasing LCS communication in the US, specifically, increasing education and outreach to eligible individuals who can benefit from LCS,” said study authors in the study.

REFERENCES

1. Lung Cancer Screening Communication in the US, 2022. JAMA Network Open. November 4, 2024. Accessed November 4, 2024. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825631?resultClick=24

2. Key Statistics for Lung Cancer. American Cancer Society. January 29, 2024. Accessed November 4, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html#:~:text=Lung%20cancer%20(both%20small%20cell,men%20and%2059%2C280%20in%20women)

3. Lung Cancer: Screening. U.S Preventive Services Task Force. March 9, 2021. Accessed November 4, 2024. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening#:~:text=The%20USPSTF%20recommends%20annual%20screening,to%20have%20curative%20lung%20surg

Q: For influenza vaccination, who is recommended to get a vaccine, and when is the preferred time frame for getting the vaccination?

Kristi Veis: Influenza vaccinations are recommended for all individuals 6 months and older. We allow our pharmacists to decide the youngest patient they feel comfortable vaccinating with the average age of 7 years old. Typically, we start vaccinating the Tuesday after Labor Day as this allows us to have a good supply on hand at all our locations. October is a big month for us promoting vaccinations to the 65+ community with a majority of our patients obtaining their influenza vaccination by the beginning of the New Year. We will never turn an arm away if we have influenza vaccine available, but our yearly cutoff is May due to expiration and credit.

Q: What is the role of the pharmacist in administering influenza vaccination?

Currently, our pharmacists are the primary vaccinators at our pharmacies and assist in the billing process as well as documenting the administration on the state portal. At a few select pharmacies, we have certified pharmacy technicians administer the vaccinations, but only after the pharmacist verifies the accuracy of the vaccine to be administered and answering any questions the patient may have.

Q: What are some strategies to best address concerns or questions that patients have about vaccination?

As was shown during the pandemic, vaccines are readily available at the pharmacy and help prevent many disease states prevalent in the US and abroad. When there’s a choice between 2 good vaccines, we typically stock 1 brand, based on price, availability, and reimbursement.

Typically, we do not advocate for one vaccine over another but will stock 1 vaccine per disease state for commonly asked vaccines thus allowing us to quickly answer questions. When questioned by patients which vaccine brand is best, we can confidently say that we only have X brand in stock, and both work similar in preventing Y. For example, we only purchased 1 brand of 65+ vaccine this year, and as it is not the high dose vaccine, our employees have been instructed to tell patients that we have regular flu vaccine or 65+ flu vaccine available. If patients have questions between high dose versus 65+, the pharmacist will go into detail on the differences. When patients ask questions about a vaccine, we give them simple details on what it typically prevents and the [adverse] effects that commonly occurs.
 

During the fall, patients come in for influenza, COVID, and other respiratory vaccines, so questions typically are asked about when they can get their dose, how long do they need to wait between different vaccines, or when can they get their next dose. Throughout the rest of the year patients come to the pharmacy because their [physician] told them to go get a vaccination which usually is one not stocked at the clinic. During this instance, we ask the patient if they know the name of the vaccine or if the [physician] was sending over a prescription for it. These are typically the patients with the most questions. Once we know the vaccine name, the pharmacist engages in conversation to answer any questions or concerns.

While vaccinating, I like to engage in conversation with patients to see if they’ve experienced [adverse] effects previously to the vaccine being administered or if they have heard of others experiencing [adverse] effects. I relay relevant information to other immunizers as well as patients that come to the pharmacy counter with similar questions. Trends are important for what is happening in the local community as that can influence whom will or will not get vaccinated for certain disease states as well as of who will want specific brands of vaccine (ie Pfizer versus Moderna) Social media also plays a part for influencing different [patient] groups.

When questions arise and the answer is not quickly available, we will investigate by using resources available to us including the drug manufacturer, CDC, and other reputable sites. We also print out information for patients who want to do their own inquiry on the vaccine prior to immunization.

Q: How can pharmacists help to increase vaccination rates in their communities?

A way that has helped in our community to increase vaccination rates is by having specific times for patients to stop in to be vaccinated instead of using an online or in-house scheduling platform. Another way is to go onsite to places, such as nursing homes, where the pharmacist can vaccinate patients at the facility or in a patient room. We work with local businesses as well as the local school districts to vaccinate teachers. Sometimes we go outside the pharmacy to a patient’s car to vaccinate. Working with other local health care and alerting local [physician’s] offices of our clinic hours and types of vaccines that the pharmacy stocks allows them to send their patients to the local pharmacy to be vaccinated.

Q: What are some challenges that pharmacists face when promoting vaccination?

Some of the challenges to promote vaccinations are reimbursement. Pharmacies need to get adequately reimbursed for the work that the pharmacist/pharmacy technician completes for the vaccination. Sometimes the local pharmacy cannot take the patient's insurance, which poses a problem for the customer who must go elsewhere to be vaccinated.

Having a dedicated vaccination room can pose a problem as it costs money to construct a room. Also, the pharmacy building itself may have a small footprint, so not enough chairs can fit for all the patients waiting to be vaccinated or for the pharmacist to watch for [adverse] effects after vaccinating. Another challenge is fridge space as we may either need to purchase bigger fridge, which costs money, or the staff must make room amongst all the current drugs and prescriptions stored within to stock the different types of vaccines needed for our patient population.

We desire to have enough people working in the pharmacy to safely engage in the practice of pharmacy as a whole. Some of the tasks during a normal business day for the pharmacy may include, time to counsel patients, check prescriptions, check in drug orders, and sell the prescriptions to patients. Sometimes there are not enough ancillary staff to do the daily tasks plus add in the time for the pharmacist to be pulled off the bench to vaccinate patients. Also, to run an offsite clinic there needs to be a second pharmacist available to work at the store. Right now, there are less pharmacists graduating from pharmacy school, and it is taking longer for them to pass their board exams thus creating a pharmacist shortage.

here are not enough hours in the day to do it all. Billing for the vaccine can take some leg work if there is insurance issues plus all the scanning of paperwork and inputting the data into the state registry takes time.

OSA is a sleep-related disorder breathing disorder that occurs when a blockage in the airway keeps an individual’s air from moving through the body while asleep. The blockage causes a lack of airflow that makes blood oxygen levels drop and leads to a survival reflex in the brain that wakes the body slightly to breathe again.^1,2 Data has shown that the disorder occurs in around 1% to 6% of children in the US, often caused by large tonsils or adenoids in the upper airway. However, the exact pathophysiologic mechanism of OSA in children remains to be a focus in research—with adenotonsillar hypertrophy as the most common cause.

Symptoms of OSA in pediatrics include loud snoring, noisy breathing, pauses in breathing that last a few seconds to a minute, mouth breathing, restlessness during sleep, sleepiness or irritability, bedwetting, morning headaches, and behavioral problems. Following, study authors noted that OSA relates to metabolic changes, growth inhibition, and cardiovascular sequelae that can significantly impact quality of life and cognitive function in children.

According to the release, the American Academy of Pediatrics suggests that primary care physicians screen for OSA in routine check-ups. However, it is often difficult to decipher primary snoring and OSA. A full night in laboratory polysomnogram (PSG) is the current standard measure of diagnosis and the severity of pediatric OSA is categorized based on the obstructive Apnea-Hypopnea Index (AHI) on PSG.

Previous studies conducted on adults with OSA suggested that vitamin D deficiency related to the disorder, allowing researchers to assess the link between low vitamin D levels with pediatric OSA in a cross-sectional study. Vitamin D deficiency was classified by 25-hydroxyvitamin (25[OH]D) less than 20 mg/mL, which occurs in 10% of children aged 1 to 11 years of age, according to study authors.

The study included 72 children, with the mean age of 6.7 years with severe OSA that were undergoing adenotonsillectomy at a tertiary care pediatric otolaryngology clinic. Using polysomnography metrics, serum 25[OH]D levels were assessed, and fasting blood samples were gathered to identify vitamin D deficiency among the children.

“A multivariable linear regression model for baseline obstructive AHI was used to determine the association with serum 25(OH)D levels after accounting for possible modifying variables including age, sex, race, BMI percentile for age, season, and history of asthma,” the study authors said in a news release.

The results displayed that the mean AHI was 42.8 and vitamin D deficiency was reported in 27 individuals included in the study. Additionally, the study authors noted that in the univariate analysis, vitamin D deficiency was connected to children younger in age, individuals that are Black, female individuals, and those with higher obstructive AHI. In the multivariable analysis, low vitamin D levels remained connected with AHI. Further results displayed that among the 72 children, 37.5% had a vitamin D deficiency, suggesting that low levels impacted higher obstructive AHI scores.

The findings suggest that further research needs to be conducted to identify if vitamin D supplementation could positively impact OSA in children, according to study authors.

REFERENCES

1. Bluher AE, Kearney T, Vazifedan T, Baldassari CM. Vitamin D Deficiency and Pediatric Obstructive Sleep Apnea Severity. JAMA Otolaryngol Head Neck Surg. Published online October 31, 2024. doi:10.1001/jamaoto.2024.3737

2. Cleveland Clinic. Obstructive Sleep Apnea. November 15, 2022. Accessed November 1, 2024. https://my.clevelandclinic.org/health/diseases/24443-obstructive-sleep-apnea-osa

3. Mayo Clinic. Pediatric obstructive sleep apnea. July 29, 2023. Accessed November 1, 2024. https://www.mayoclinic.org/diseases-conditions/pediatric-sleep-apnea/symptoms-causes/syc-20376196#

4. Cedars Sinai. Obstructive Sleep Apnea in Children. News release. Accessed November 1, 2024. https://www.cedars-sinai.org/health-library/diseases-and-conditions---pediatrics/o/obstructive-sleep-apnea-in-children.html

This situation creates uncertainty for 503A and 503B compounders. Although the FDA clarified that it intends consistent enforcement discretion for all sterile compounders, 503A compounders remain uncertain about their status. The Alliance for Pharmacy Compounding (APC) has requested clarification on whether this enforcement discretion applies to them.

According to Rumore, the FDA’s may be moving toward reducing compounding for GLP-1 drugs, such as tirzepatide and semaglutide (Ozempic, Wegovy, Rybelsus; Novo Nordisk), which compounders rely on amid shortages. The manufacturer of semaglutide, for instance, filed a petition to add it to the FDA’s Difficult to Compound list, claiming safety concerns due to the drug’s complexity.

Looking forward, Rumore advises compounders to monitor tirzepatide’s status closely, as the FDA’s upcoming decision could limit compounding to specific circumstances requiring a prescriber’s justification of a significant medical need. This increased regulatory focus, combined with manufacturer litigation, underscores the need for careful documentation and adherence to FDA guidance to ensure compliant compounding practices.

Pharmacy Times: What was the decision on 503A and 503B compounding, purchasing, and dispensing tirzepatide, and what is the impact of this decision?

Martha M. Rumore, PharmD, Esq, MS, LLM, FAPhA: After FDA removed tirzepatide from the 506e shortage list, a lawsuit was filed against the FDA by the OFA and North American Custom Laboratories, LLC (see Outsourcing Facilities of America; North American Custom Laboratories, LLC DB/A Farmakeio Custom Compounding v United State Food and Drug Administration and Dr. Robert Califf, Civ. Action No. 4:24-cv953. Filed October 7, 2024 US District Court for the Northern District of Texas). OFA is a trade association representing 503B outsourcing facilities, and North American Custom Laboratories is a Texas-based 503B outsourcing facility.

The lawsuit filed is based upon claims that FDA acted in a “reckless and arbitrary” way to deprive patients of compounded tirzepatide. The lawsuit asserts that the FDA’s decision to remove tirzepatide from the 506e shortage list was note based on an appropriate evaluation of the tirzepatide shortage and supply.
 

Finally, the lawsuit asserts that FDA’s action was a “substantive” rule, and that FDA did not follow the procedure for substantive rules under the Administrative Procedures Act (APA). The lawsuit then asserts that the shortage of tirzepatide is not resolved, and that FDA failed to engage in meaningful inquiry and instead relied on a one-sided presentation to the agency by the manufacturer. To date, there has not been any similar lawsuit filed by 503A compounders.

On October 11, 2024, FDA submitted a Motion for Voluntary Remand and Stay for the purpose of “giving the agency the opportunity to reevaluate the decision at issue in view of the plaintiffs challenges to it” and give FDA an opportunity to cure any legal APA errors (see Case 4:24-cv-00953P. Document 27. Filed October 11, 2024).

The Motion was granted. Importantly, the FDA stated in the Motion that it will not take enforcement action against 503Bs for compounding tirzepatide as they did while the drug was on the FDA shortage list. This enforcement discretion will last until 2 weeks beyond FDA’s reconsideration of the decision, which is due by November 21, 2024. The enforcement discretion did not mention 503A compounders, leading to confusion for that group of compounders.

The APC, a trade group representing 503A compounders, submitted a written request to FDA for clarification regarding whether the enforcement discretion extends to 503A compounding as well. On October 17, 2024, FDA issued a letter to APC and then provided clarification on the FDA website essentially extending enforcement discretion to “sterile compounders” and that FDA “intends to treat compounders consistently at this time.”

Pharmacy Times: In the legal case challenging the FDA's decision, what are your thoughts on how the FDA may respond, and is there a precedent for this case that may inform a potential decision in this case?

Rumore: No one can predict how FDA will respond and there is no legal precedent. However, on October 30, 2024, FDA amended all listings for semaglutide on the 506e shortage list as “available.” This means that FDA is most likely reviewing nationwide availability and may be removing semaglutide from the shortage list sooner rather than later. It is no revelation that FDA has been trying to limit compounding of GLP-1s.

Pharmacy Times: What does the future hold for the availability of tirzepatide?

Almost 50 people have been hospitalised after using GLP-1 receptor agonists to lose weight in the UK, the MHRA has reported as it urged pharmacists and other healthcare professionals to advise patients of side effects and report the misuse of these products. 

In a drug safety update published today (October 24), the MHRA said that as of August 16 this year it had received 5,073 reports of “common gastrointestinal reactions” associated with using the products for weight loss, out of which 46 had been hospitalised. 

The medicines safety watchdog said it had also received Yellow Card reports of severe dehydration following gastrointestinal drug reactions, “including for individuals who may not meet the prescribing criteria and may have used these medicines inappropriately for weight loss” but added that it is “difficult to confirm the inappropriate use or misuse” of drugs from the data received. 

With COVID-19, influenza, respiratory syncytial virus (RSV), and other viruses now circulating, the time for pharmacists to get up to date on the latest vaccine recommendations is now, said David Ha, PharmD, BCIDP, manager of infectious diseases at Stanford Health Care, in a session at the National Community Pharmacists Association 2024 Annual Convention and Expo.

Thus far this year, Ha said CDC data are showing a decent uptick in COVID-19 cases as well as rhinoviruses and adenoviruses. Although the increase of influenza and RSV cases hasn’t yet begun, Ha said it’s inevitable. The seasonal peak hospitalization burden for 2024 and 2025 is expected to be similar or slightly lower than the 2023-2024 season.

“But we’ve been fooled before, so just a reminder to keep on your toes with that,” Ha said. “Now or yesterday was the time to vaccinate.”

With COVID-19, influenza, respiratory syncytial virus (RSV), and other viruses now circulating, the time for pharmacists to get up to date on the latest vaccine recommendations is now, said David Ha, PharmD, BCIDP, manager of infectious diseases at Stanford Health Care, in a session at the National Community Pharmacists Association 2024 Annual Convention and Expo.

Thus far this year, Ha said CDC data are showing a decent uptick in COVID-19 cases as well as rhinoviruses and adenoviruses. Although the increase of influenza and RSV cases hasn’t yet begun, Ha said it’s inevitable. The seasonal peak hospitalization burden for 2024 and 2025 is expected to be similar or slightly lower than the 2023-2024 season.

“But we’ve been fooled before, so just a reminder to keep on your toes with that,” Ha said. “Now or yesterday was the time to vaccinate.”

Independent pharmacy staff continue to be driven by the desire to improve patient outcomes in their communities, according to the 2024 National Community Pharmacists Association Digest, sponsored by Cardinal Health.

Nearly 19,000 independent pharmacies continue to work across the country, with more than 200,000 employees and millions of patients, according to the Digest. In addition to dispensing more than 1.1 billion prescriptions in 2023, these pharmacies are continually expanding their clinical services, including point-of-care testing, immunizations, blood pressure monitoring, diabetes management, smoking cessation, weight management, and more.

Independent pharmacies are a significant portion of the pharmacy market, with 18,984 locations as of June 2024. This is compared with 19,075 traditional chain pharmacies, 9152 supermarket pharmacies, and 7225 mass merchants. The Digest emphasized that no single pharmacy chain has more stores than all independents combined, representing 35% of all retail pharmacies in the US and a $94.9 billion marketplace. Importantly, however, the number of independent pharmacies is down from 19,432 in the 2023 Digest, representing a loss of more than 1 pharmacy per day.

Cost savings are an important benefit of independent pharmacies, where 83.1% of prescription drugs are filled with a generic, on average. However, this number trended down in the 2024 digest, potentially due to the explosion of glucagon-like peptide-1 (GLP-1) agonists, which currently have no available generic options.

Patients also visit independent pharmacies for the crucial clinical services they increasingly provide, particular in areas where the pharmacist may be the only health care provider in the county. Although dispensing prescription medications is a significant part of pharmacies’ business model, the Digest emphasized that growing the bottom line is going to rely on products and services that do not have a National Drug Code number.

Independent pharmacies are one of the leading destinations for vaccines, with influenza vaccines offered at 91% of independent pharmacies according to the Digest. Most locations also offer at least 1 other vaccine such as COVID-19, pneumococcal, respiratory syncytial virus, zoster, or travel vaccines.

Independent pharmacists also frequently partner with staff in long-term care (LTC) facilities in their communities to provide medications and medication-related care for residents. They also provide many essential services for this patient population, such as adherence packaging, nutrition assessment and support, home infusion therapy, durable medical equipment, ostomy supplies, and pain management.

According to the report, 52% of independent community pharmacists provided LTC services in 2023, serving an average of 27 beds for skilled nursing facilities. This number was down from an average of 44 beds in 2022. Among pharmacies providing LTC services, they also reported an average of 80 patients receiving LTC-at-home services.

Most independent pharmacies also offer adherence services such as medication synchronization. Appointment-based models for medication synchronization can be particularly beneficial, both for patients and pharmacy staff. In the Digest, 94% of independent community pharmacies reported offering medication synchronization services to synchronize all chronic medications to a monthly pick-up date, and 63% report that a pharmacist meets with patients as needed to review medications.

Like immunizations and medication counseling, pharmacy-based labs with a Clinical Laboratory Improvement Amendments (CLIA) waiver offer crucial services for patients who may have limited access to a physician. CLIA-waived tests can provide results in minutes, giving pharmacists information to determine whether they should provide further counseling or a referral to a higher level of care.

Of the 52% of pharmacies with a laboratory, the most commonly offered tests are influenza (58%), blood glucose (46%), hemoglobin A1c (40%), and lipids (24%). Another 36% report testing for COVID-19, but the Digest noted that those responses are a mixture of point-of-care tests and specimen collection for off-site laboratory analysis.

Of course, despite the growing number of services and the value independent pharmacies provide to their communities, challenging economic trends continue. A survey of community pharmacists in February 2024 found that many are struggling to manage losses caused by direct and indirect remuneration (DIR) fees from pharmacy benefit managers (PBMs). More than 50% said they are losing money on at least 30% of the prescriptions they fill, and 85% said the “DIR hangover” threatens the viability of their business. Alarmingly, 32% said they were considering closing their business within the calendar year.

Furthermore, 97% of respondents reported drug shortages, including 87% who reported a shortage of Adderall or generics and 96% who reported shortages or backorders of GLP-1s. Furthermore, 67% said they are having a difficult time filling open positions and 76% said the most difficult position to fill was pharmacy technicians.

The Digest noted that tax incentives and revenue during the COVID-19 pandemic were a “critical lifeline” keeping independent pharmacies afloat in recent years. With the decline in demand for COVID-19 services, the effects of below-cost reimbursements is taking a heavy toll.

Independent pharmacies have proven to be resilient in the face of adversity by adapting to changing industry trends and patient demands. This ability to innovate and provide tailored services will continue to be a valuable asset to their communities in the future, as they continue navigating challenging financial conditions.

REFERENCE

2024 NCPA Digest. National Community Pharmacists Association. October 27, 2024. Accessed October 27, 2024.

Endometriosis is a chronic inflammatory gynecological disease that affects an estimated 10% (190 million) of reproductive-age women and is characterized by endometrial-like tissue present outside of the uterus, resulting in severe pelvic pain, heavy bleeding during or between periods, bloating and nausea, fatigue, depression or anxiety, as well as infertility, in some cases. Historically, endometriosis was believed to be a gynecological disease that only affected women and emerged from retrograde menstruation; however, emerging studies indicate that this definition is outdated and neglects the true manifestations of the disease.

Authors from a study published in The Lancet explained that endometriosis is a systemic disease that affects metabolism in liver and adipose tissue, leading to systemic inflammation and altering gene expression in the brain that causes pain sensitization and mood disorders. Their definition recognizes the diseases manifestations and complications beyond the pelvis, opening doors for improved understanding and treatment.

As acknowledgment of the disease as truly being systemic grows, its many impacts on the other organ systems are being discovered. In a separate study, authors aimed to evaluate endothelial dysfunction, arterial stiffness, and skin advanced glycation end-products (AGEs) accumulation in patients with endometriosis, which has been largely understudied. They hypothesized that these complications lead to the risk and prevalence of ischemic heart disease, cerebrovascular disease, heart failure, dyslipidemia, arrhythmias, and stroke in patients with endometriosis.

In the study, the authors matched the age, body mass index, and blood pressure values of 21 patients with endometriosis and 24 healthy controls. They used an Endo-PAT 2000 device for non-invasive assessment of endothelial function, expressed as Reactive Hyperemia Index (RHI), and arterial stiffness, expressed as Augmentation Index (AI) and Augmentation Index at 75 heart beats/min (AI75). An AGE Reader device was used for non-invasive evaluation of skin AGE level accumulation.

According to the results, patients with endometriosis had lower mean RHI values (1.69 ± 0.54 vs. 2.02 ± 0.48, p = 0.037) and a higher prevalence of endothelial dysfunction, (52.4% vs. 20.8%, p = 0.027) compared with healthy controls, as well as higher skin AGE levels (2.00 ± 0.57 vs. 1.70 ± 0.24, P = 0.013). Both endothelial dysfunction and elevated AGE skin accumulation are well-known preclinical indicators of increased CVD risk.

The findings support the complexity of endometriosis and its impact on various parts of the body, as well as suggest a greater need for comprehensive CVD risk assessment in patients with endometriosis. The initial findings add to the growing body of evidence redefining endometriosis and dispelling common misconceptions around the disease, creating more opportunities for research and treatment.

REFERENCES

1. Smyk J, Danielecka Z, Kotowska M, et al. Cardiovascular risks and endothelial dysfunction in reproductive-age women with endometriosis. Sci Rep. October 15, 2024. doi:10.1038/s41598-024-73841-7

2. Endometriosis. World Health Organization. March 24, 2023. Accessed October 18, 2024. https://www.who.int/news-room/fact-sheets/detail/endometriosis#:~:text=Overview,period%20and%20last%20until%20menopause

3. Endometriosis is more than just ‘painful periods.’ Yale Medicine. August 17, 2023. Accessed October 18, 2024. https://www.yalemedicine.org/news/endometriosis-is-more-than-painful-periods

4. Taylor H, Kotlyar A, Flores V. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. The Lancet. doi:10.1016/S0140-6736(21)00389-5

5. Farland L, Degnan W, Bell M, et al. Laparoscopically confirmed endometriosis and risk of incident stroke: a prospective cohort study. Stroke. July 21, 2022. doi:10.1161/STROKEAHA.122.039250

NHS England has announced that the Pharmacy First consultation threshold for monthly payments will remain at 20 consultations until December 2024.

Speaking at The Pharmacy Show on 14 October 2024, Ali Sparke, director for pharmacy, optometry, dentistry and the NHS standard contract at NHS England, said that, following discussions with Community Pharmacy England (CPE), “we are going to confirm the 20 minimum activity requirements in October [and] keep it at that level for November and December”.

“We’re going to move it to 25 [consultations] in January and February, before reaching 30 [consultations], as planned by the end of this financial year [March 2025],” he added.

“It’s quite a big departure from where we were before, but we think it’s really important to balance the levels of payment going in the sector, to continue to support pharmacies during this kind of establishment period of Pharmacy First.”

The threshold is the number of consultations participating pharmacies must complete per month to trigger a £1,000 monthly payment, which was due to increase to 30 consultations in October 2024, as outlined in the Department of Health and Social Care (DHSC)’s pre-planned schedule. 

However, CPE confirmed on 30 September 2024 that the October threshold would be reduced to 20 consultations, following concerns from the negotiator that contractors would miss out on the monthly payment.

The decision followed a similar one taken to cut the planned threshold for consultations in August 2024 from 20 consultations to 15 consultations.

In September 2024, analysis of NHS Business Services Authority (NHSBSA) data by The Pharmaceutical Journal revealed that community pharmacies have missed out on almost £10m in funding since the launch of Pharmacy First on 31 January 2024 because they have not been hitting monthly thresholds.

The analysis revealed that 9,600 pharmacies in England missed the consultation threshold to qualify for the monthly fixed payment of £1,000 between February 2024 and May 2024.

After March 2025, the government announced in November 2023 that pharmacies will also need to provide the NHS ‘Community pharmacy contraception service’, and NHS ‘Blood pressure checks service’, in addition to Pharmacy First, to qualify for the £1,000 payment.

Sparke confirmed to Pharmacy Show delegates that around 7,300 pharmacies (69%) have so far signed up to deliver all three services.

“We’ve got a really, really high proportion of pharmacies who are signed up to Pharmacy First,” he said.

“But also, really importantly, we’ve got 7,300 pharmacies, about 69%, that have signed up to all three proposed services.

“I think [this] helps us along that road in providing a really clear message to patients on the kinds of services they can get… that’s something to really be celebrated,” he said.

Commenting on the government’s decision to reduce Pharmacy First thresholds, Janet Morrison, chief executive of CPE, said: “Whilst not as large a reduction in the thresholds as we wanted, these changes at least indicate ministers are taking a much more pragmatic approach to Pharmacy First payment thresholds.

“This has been one of the key issues that we have been raising with the new government, alongside the desperate wider financial position for community pharmacies, so we are grateful that some longer-term adjustments have now been made.

“We still need NHS England to effectively advertise the service to the public on an ongoing basis and to increase referral rates from general practices.

“It is critical that this now happens to allow patients and the public to receive care closer to home; to help improve access to general practice; and to allow community pharmacies to maximise the amount of allocated funding that they can earn from this important service,” she said.

Paul Rees, chief executive of the National Pharmacy Association, commented: “This latest revision to the Pharmacy First thresholds shows that the government and NHS England are at least listening to the sector’s concerns and recognise that the situation on the ground is incredibly challenging.”

How prevalent is iron deficiency among the American public? Researchers of a recent study published in JAMA sought answers and discovered that absolute and functional iron deficiency affect a large proportion of American adults even in the absence of anemia, heart failure, chronic kidney disease, or a current pregnancy.

Out of the study sample of 8,021 adult participants, an estimated 14% of U.S. adults had absolute iron deficiency, and an estimated 15% had functional iron deficiency. Absolute iron deficiency results from a severe reduction or absence of iron stores. Functional iron deficiency occurs in the presence of adequate iron stores but insufficient iron availability. Data were taken from the National Health and Nutritional Examination Survey 2017 to 2020 prepandemic cycle.

Researchers hypothesized that dietary iron intake, food security, and alcohol use would be associated with iron deficiency, but did not find clear patterns to support these nutritional factors as potential causes. Approximately 27% of participants reported marginal, low, or very low food security.

“This cross-sectional study indicates that both absolute and functional iron deficiency affect a large proportion of adults in the U.S., especially among those without conditions often screened for iron deficiency,” noted study authors. “Moreover, iron supplement use was infrequent among adults with iron deficiency. Absolute and functional iron deficiency may be a widespread, underrecognized public health problem.”

CDC recommends iron screening for high-risk groups, but there is no clear recommendation for iron deficiency surveillance in the general population.

According to the study authors, current screening recommendations may miss 70% of iron deficiency cases among children and during pregnancy—populations who are at high risk of developing iron deficiency or anemia and who are more commonly tested.

Although most research has focused on adverse outcomes among people with iron deficiency and anemia, iron deficiency affects nonerythropoietic tissue, such as skeletal and cardiac muscle, in the absence of anemia, according to the research.

A Carnegie Mellon University-led team of researchers has secured an award of up to $34.9 million from the Advanced Research Projects Agency for Health (ARPA-H). The funds will fast track a bioelectronic implant that could radically improve treatment options and significantly reduce the cost of care for patients with obesity and Type 2 diabetes.

The award will drive the accelerated development and testing of "Rx On-site Generation Using Electronics (ROGUE)," a bioelectrical device that hosts a "living pharmacy," consisting of engineered cells that produce biological therapy to treat Type 2 diabetes and obesity. The device will offer continuous, adjustable, and low-cost therapy deployment via a minimally invasive procedure performed in an outpatient clinic. Additionally, in a stark contrast from the traditional delivery of biologics, it will eliminate the need for weekly injections, trips to the pharmacy, and careful storage of expensive medications.

"This project is the peak deployment of several core technologies we have developed and refined over the past five years, as part of the Bioelectric Medicine Initiative at Carnegie Mellon University," said Carnegie Mellon University materials science and bioengineer Tzahi Cohen-Karni, who serves as primary investigator on the ARPA-H award. "Bioelectronic devices offer a myriad of benefits, including adjustable therapy delivery, dynamic monitoring, and reduced biologics healthcare costs. We are leveraging our collective strengths to develop an effective and sustainable solution to reduce the burden of chronic care for two global epidemics – obesity and Type 2 diabetes."

ARPA-H is a federal funding agency established in 2022 to support research that has "the potential to transform entire areas of medicine and health."

The collaborative team includes 17 co-PIs from Boston University, Georgia Institute of Technology, Northwestern University, Rice University, UC Berkeley, the Mayo Clinic and New York City-based Bruder Consulting and Venture Group. It includes engineers, physicians and multidisciplinary specialists in synthetic biology, materials science, electrical engineering, and other fields.

"The Rice Biotech Launch Pad is determined to facilitate the clinical translation and commercialization of this breakthrough and market disruptive, first-in-class technology," said Rice University bioengineer Omid Veiseh, co-investigator on the ARPA-H award.

We are developing a minimally invasive implant that can produce a year's supply of a treatment for chronic diseases like Type 2 diabetes and obesity. With a simple, once-a-year procedure, ROGUE will replace current treatments that have to be administered daily, weekly or monthly."

Omid Veiseh, Rice University

This effort is funded under ARPA-H's REACT program and includes funding for a first-in-human clinical trial for patients facing obesity and Type 2 diabetes. The trial preparation is slated to begin in the fifth year of the six-year project.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) poses a significant global health burden. COPD is characterized by a marked decrease in airflow in the lungs that results in dyspnea and cough. Patients may develop acute exacerbation of COPD (AECOPD), a complication characterized by increased symptom severity. AECOPD diagnosis involves ruling out other potential causes of the symptoms. AECOPD treatment includes antibiotics, corticosteroids, and bronchodilators. Nonpharmacologic treatments not only can help relieve patients’ AECOPD symptoms but may also prevent future exacerbations. Pharmacists are instrumental in the care of patients with AECOPD.

Chronic obstructive pulmonary disease (COPD), which involves inflammation in the small airways and alveoli of the lungs, leads to narrowed airways, reduced elasticity, and increased sputum.^1,2 These changes result in symptoms such as dyspnea, cough, and exacerbations. COPD is attributable to multiple factors, including genetics and environmental exposures.^1,2 According to the World Health Organization, COPD was the third-highest cause of death worldwide in 2019, and it is the seventh leading cause of disability-adjusted life-years.³ In 2010, the average annual direct healthcare cost for COPD in the United States exceeded $6,000 per patient.⁴ Furthermore, in 2018, COPD patients in the U.S. lost an average of 5 workdays per year.⁴

Acute exacerbation of COPD (AECOPD) is a burdensome complication responsible for the lion’s share of COPD’s financial strain on the healthcare system.^1,4,5 An exacerbation is defined as an acute increase in dyspnea and/or cough and sputum production.^1,6 AECOPD is characterized by increased inflammation, gas trapping, and sputum production, which leads to the marked increase in dyspnea.^1,6 Tachypnea and tachycardia may also occur during an exacerbation.^1,6

Diagnosis

To diagnose AECOPD, other causes of the patient’s symptoms must be ruled out. Pneumonia, pulmonary embolism, and heart failure exacerbation are the most common conditions that can mimic AECOPD.¹ Tests that are helpful for narrowing down the diagnosis include chest radiography, d-dimer levels, and pro–B-type natriuretic peptide levels.^1,7,8 The phrasing “exacerbation of respiratory symptoms in patients with COPD” has been suggested to highlight for clinicians the importance of identifying the cause of AECOPD symptoms and pursuing more appropriate treatment options based on the contributing factors.⁷

After other causes are ruled out, the severity of the symptoms must be evaluated.¹ AECOPD severity is determined by assessing the treatments used after the episode. If short-acting bronchodilators (SABDs) are the only medications used, the AECOPD is classified as mild; moderate AECOPD is treated with SABDs and corticosteroids with or without antibiotics; and severe AECOPD requires treatment in the hospital or emergency department.¹ These classifications are limiting because clinicians are using the treatment to define the severity of AECOPD instead of using the severity to define the treatment. AECOPD treatment could be more precise with a new severity-grading system, such as the Rome proposal.⁶

The Rome proposal uses vital signs and laboratory testing to stratify the severity of COPD exacerbations in both hospital and primary care settings.^1,6 This strategy employs a visual analogue scale for dyspnea in addition to respiratory rate, heart rate, and oxygen saturation as the crucial elements for differentiating between mild and moderate exacerbations (TABLE 1).^1,6

TREATMENT

Antibiotics

Although antibiotics can be beneficial in some cases of AECOPD, they are not always necessary given that viruses are responsible for most AECOPD occurrences.¹ Biomarkers such as procalcitonin and C-reactive protein (CRP) have been studied to consider their role in determining whether to prescribe antibiotics for AECOPD. CRP-guided therapy can reduce antibiotic use in AECOPD without compromising disease-specific quality of life; nonetheless, its routine application is discouraged owing to conflicting data on its clinical utility.^1,9 One study of patients with AECOPD and a procalcitonin level <0.1 ng/mL who received either broad-spectrum antibiotics or placebo found no significant differences in treatment-success rate on day 10, length of hospital stay, recurrence of AECOPD in 30 days, intubation, hospital readmission, or mortality.¹⁰ However, in a 2020 meta-analysis of randomized, controlled trials (most of them involving inpatients), procalcitonin had no statistically significant effect on duration of antibiotic treatment in AECOPD, and it did not change clinical outcomes such as length of hospital stay or mortality; in fact, the use of procalcitonin-guided therapy led to worse outcomes in ICU patients.¹¹ Based on these conflicting results, it is not currently recommended to use procalcitonin to guide antibiotic treatment in AECOPD.¹

Currently, guidelines recommend antibiotics for AECOPD in the following three scenarios: patients who have the three cardinal symptoms of increased sputum volume, sputum purulence, and dyspnea; patients who have two of the three cardinal symptoms, one of these being increased sputum purulence; and patients who are on mechanical ventilation.¹

In a retrospective cohort study of mostly hospitalized patients with AECOPD, those who received antibiotics within the first 2 days of admission had significantly lower rates of readmission, need for mechanical ventilation, and inpatient mortality.¹² In another study, antibiotic adminstration in ICU patients resulted in reduced mortality and decreases in treatment failure, length of ICU stay, need for additional antibiotics, and duration of mechanical ventilation.¹³

The bacteria most likely to cause AECOPD are Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa.¹⁴ Risk factors for P aeruginosa include previous isolation of P aeruginosa, recent hospitalization, systemic corticosteroid use, severe bronchiectasis, and previous antibiotic exposures.^15,16 The antibiotics usually used for AECOPD are aminopenicillin with clavulanic acid, macrolides, tetracyclines, or fluoroquinolones.¹ Although guidelines do not give specific recommendations on which of these antibiotics is the drug of choice, one pooled analysis showed no significant clinical difference in patients with lower respiratory tract infections (including AECOPD) treated with amoxicillin/amoxicillin-clavulanate versus azithromycin; however, azithromycin was better tolerated.¹⁷ The recommended duration of antibiotic use is ≤5 days.¹ In two meta-analyses, there was no clinical difference in patients with AECOPD receiving 5 days versus 7 to 10 days of antibiotics, and patients in the longer-duration group had more adverse effects.^18,19

Corticosteroids

Glucocorticoids benefit hospitalized AECOPD patients by enhancing oxygenation, improving recovery time, reducing the relapse risk, and shortening the length of hospital stay. Although most hospitalized patients with AECOPD should receive glucocorticoids, emerging evidence indicates that eosinophils may predict the response to glucocorticoids, thereby guiding their use in AECOPD patients.²⁰

Corticosteroids may be administered via inhalation, orally, or IV. No differences have been shown between oral and IV routes in terms of treatment failure, relapse, or mortality, but there might be more adverse drug reactions with parenteral administration.^21,22 Parenteral corticosteroids may be considered in patients who did not initially respond to oral corticosteroids or are unable to swallow. High-dose inhaled budesonide was noninferior to systemic corticosteroids regarding changes in forced expiratory volume in 1 second (FEV₁); however, it was inferior in terms of oxygenation. High-dose inhaled budesonide may cause less hyperglycemia.²³

The recommended oral corticosteroid treatment for AECOPD is prednisone 40 mg daily (or equivalent).¹ The Global Initiative for Chronic Obstructive Lung Disease guideline recommends a duration of 5 days, whereas the European Respiratory Society/American Thoracic Society guideline recommends a duration of up to 14 days.^1,24 The REDUCE trial demonstrated no difference in time to next exacerbation or recovery time in patients who received 5 days versus 14 days of prednisone 40 mg daily, but the shorter treatment course had the advantage of significantly reduced glucocorticoid exposure.²⁵

Bronchodilators

Short-acting beta₂ agonists (SABAs) are a mainstay of therapy in AECOPD.¹ The addition of a short-acting muscarinic antagonist (SAMA) to the SABA may be considered. Although the SAMA/SABA combination has demonstrated benefit in stable COPD compared with either agent alone, data on its use in AECOPD are limited.²⁶ Based on its results in stable COPD, however, the combination is commonly used in practice.

These medications are available as metered-dose inhalers, soft mist inhalers, and nebulizers. One systematic review found no difference in FEV₁ changes in patients using inhalers versus nebulizers.²⁷ In practice, clinicians may prefer to prescribe the nebulizer because of its ease of use, especially in patients who have difficulty using an inhaler.

Current guidance is to continue the patient’s home inhalers—which may include long-acting muscarinic antagonists and long-acting beta₂ agonists—in those experiencing AECOPD.¹ These medications bind to the same receptors as their short-acting counterparts and may be considered a duplication of therapy. Continuing a patient’s home inhalers may provide little to no additional benefit while also increasing the risk of possible adverse drug effects and unnecessary drug costs.²⁸ Further research is needed to determine whether there is benefit or harm to continuing a patient’s home bronchodilators during AECOPD.

Respiratory Therapy

Respiratory therapy is an essential part of the treatment of AECOPD. Oxygen saturation should be maintained between 88% and 92%, as this is the safest range for AECOPD.^1,29 Blood gases should be monitored frequently during administration of oxygen therapy.¹

In severe AECOPD, ventilation support may be required. Noninvasive mechanical ventilation (NIV) is preferred over invasive mechanical ventilation (IMV) for initial ventilation support.¹ NIV is indicated in patients experiencing respiratory acidosis, persistent hypoxia, or severe dyspnea.^1,30 IMV is indicated for NIV failure or intolerability, diminished consciousness, uncontrolled psychomotor agitation, aspiration/persistent vomiting, hemodynamic instability, or severe ventricular or supraventricular arrhythmia.¹

Additional Therapy Considerations

Nonpharmacologic treatments not only can help relieve patients’ AECOPD symptoms but may also prevent future exacerbations. Smoking cessation, vaccinations, and pulmonary-rehabilitation plans should be discussed with the patient before discharge. Data suggest that smoking cessation should be discussed at all points in COPD therapy, including after an AECOPD and at discharge.^1,31,32

Influenza, pneumococcal, COVID-19, respiratory syncytial virus (RSV), Tdap (tetanus, diphtheria, pertussis), and shingles vaccines are recommended for eligible patients because they reduce the risk of AECOPD.^1,33 PCV20 (pneumococcal conjugate vaccine) alone may be administered at discharge to any COPD patient aged 19 years or older who has not previously received a pneumococcal vaccine.^1,31,34 Patients who previously received PPSV23 (pneumococcal polysaccharide vaccine) may get either PCV15 or PCV20 if 1 year or longer has passed since the PPSV23 vaccination. Patients who have received PCV15 should get PPSV23 if 1 year or longer has passed since the PCV15 vaccination.^1,34 The RSV vaccine is recommended in COPD patients aged 60 years or older.^1,34 It is important to regularly check the CDC’s vaccination guidelines for any updates to the immunization schedule.

Pulmonary rehabilitation consists of education, exercise, and behavioral changes that aim to improve the patient’s physiologic and psychological condition.¹ Because pulmonary rehabilitation reduces the risk of hospitalization after recent (≤4 weeks prior) exacerbations, this program should be discussed with the patient before discharge.^1,31,32 Pulmonary-rehabilitation programs may be initiated as soon as 1 month after the AECOPD.³⁵ However, it is crucial to account for reduced ventilatory capacity in these patients to avoid precipitating another exacerbation.³⁶

THE PHARMACIST’S ROLE

Pharmacists are instrumental in the care of patients with AECOPD. Counseling these patients on proper inhaler techniques to prevent exacerbations is vital to successful disease control. Pharmacist collaboration with the medical team enables optimization of the medications used to treat a patient’s AECOPD, including the appropriate indication, route, and dosage. In the era of antimicrobial stewardship, pharmacists can ensure the judicious use of antibiotics in patients with AECOPD. Pharmacists can also recommend the implementation of nonpharmacologic therapies, including vaccines.

The FDA has granted accelerated approval to tarlatamab-dlle (Imdelltra; Amgen Inc) to treat extensive stage small cell lung cancer (ES-SCLC) that has progressed during or after platinum-based chemotherapy treatment.¹

According to the National Cancer Institute, the prognosis for individuals diagnosed with SCLC is not optimal, despite treatment advancements over the past 25 years. If not treated, the median survival for SCLC is only 2 to 4 months. When treated, just 10% of individuals remain disease free during the 2 years from the start of treatment. The study authors noted that even among those who receive treatment, only 5% to 10% survive 5 years.²

Symptoms of SCLC can include inappropriate antidiuretic hormone secretion, Cushing syndrome from secretion of adrenocorticotropic hormone, paraneoplastic cerebellar degeneration, and Lambert-Eaton myasthenic syndrome, according to study authors.²

Tarlatamab is a first-in-class immunotherapy that binds to DLL3 tumor cells and CD3 T-cells, to kill DLL3-expressing SCLC, according to study authors.³

"After decades of minimal advancements in the SCLC treatment landscape, there is now an effective and innovative treatment option available," said Laurie Fenton Ambrose, co-founder, president, and CEO of GO2 for Lung Cancer, in a press release. "Today's FDA approval marks a significant milestone for the SCLC community as the availability of a targeted bispecific therapy brings forward new possibilities to those living with this aggressive disease."³

The accelerated approval was granted based on results from the DeLLphi-301 (NCT05060016) trial, an open-label, multicenter, multi-cohort study that assessed tarlatamab on 99 patients with ES-SCLC who experienced disease progression after platinum-based chemotherapy. The individuals received tarlatamab until signs of disease progression or unacceptable toxicity, according to study authors.¹ The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), according to study authors.¹

"In the DeLLphi-301 trial, the median overall survival was 14.3 months, with 40% of patients responding to treatment with tarlatamab. These responses were remarkably durable, representing a major advancement in the SCLC treatment paradigm," Ambrose said.³

Additionally, the study authors noted that the median DOR was 9.7 months.¹

The recommended initial dose of tarlatamab is an intravenous 1 mg infusion for 1 hour on cycle 1, day 1, then 10 mg on cycle 1 day 8 and 15, continued every 2 weeks.¹

The study authors noted that the most common adverse events included CRS, fatigue, pyrexia, dysgeusia, decreased appetite, musculoskeletal pain, constipation, anemia, and nausea.³

"The FDA's approval of IMDELLTRA marks a pivotal moment for patients battling ES-SCLC. This DLL3-targeting therapy in ES-SCLC comprises a transformative option demonstrating long-lasting responses in pretreated patients," said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen, in a press release. “This approval further demonstrates our commitment to addressing aggressive cancers through our second FDA-approved Bispecific T-cell Engager (BiTE®) molecule. IMDELLTRA offers these patients who are in urgent need of new innovative therapies hope, and we're proud to deliver this long-awaited effective treatment to them."³

References

1. FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer. FDA. News release. May 16, 2024. Accessed May 17, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer.

2. Small Cell Lung Cancer Treatment (PDQ®)–Health Professional Version. National Cancer Institute. News release. March 1, 2024. Accessed May 17, 2024. https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq.

3. FDA Approves IMDELLTRA™ Tarlatamab-DLLE, The First and Only T-Cell Engager Therapy For The Treatment of Extensive Stage Small Cell Lung Cancer. PR Newswire. News release. May 16, 2024. Accessed May 17, 2024. https://www.prnewswire.com/news-releases/fda-approves-imdelltra-tarlatamab-dlle-the-first-and-only-t-cell-engager-therapy-for-the-treatment-of-extensive-stage-small-cell-lung-cancer-302148431.html.