Alana Hippensteele, Editor

The FDA has approved the monoclonal antibody mepolizumab (Nucala, GlaxoSmithKline plc), as a treatment for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Mepolizumab works by targeting interleukin-5 (IL-5) and is the first anti-IL-5 biologic to be approved by the FDA for use in adult patients with CRSwNP in the United States.

This approval is a new indication for mepolizumab, making it an add-on maintenance treatment for adult patients with CRSwNP 18 years of age and older who have shown a previous inadequate response to nasal corticosteroids. Mepolizumab has also been previously approved for use in 3 other eosinophilic-driven diseases, the first of which was severe eosinophilic asthma among pediatric patients 6 years of age and older.

CRSwNP, which arises from inflammation in different tissues, currently affects more than 5 million people in the United States. This inflammation is also associated with increased levels of the white blood cell eosinophils. With their eosinophil levels raised, patients with CRSwNP can develop nasal polyps in the sinuses and nasal cavity. CRSwNP can also lead to chronic symptoms of nasal obstruction, loss of smell, facial pressure, and nasal discharge.

“More than 5 million people in the US suffer with chronic rhinosinusitis with nasal polyps and today’s approval provides these patients with the first anti-IL-5 treatment option and an alternative to surgery to help reduce symptoms of this disease,” Hal Barron, MD, chief scientific officer and president R&D, GSK, in a press release.

Officials at the FDA based the approval of mepolizumab on the results of the SYNAPSE study, which investigated the effect of mepolizumab against the placebo in more than 400 patients with CRSwNP. The data showed that mepolizumab significantly improved the reduction in size of nasal polyps and nasal obstruction.

During the study, the patients received the standard care for CRSwNP. All patients included in the study had a history of prior surgery—approximately 1 in 3 had 3 or more surgeries—and needed additional surgery due to the severity of their symptoms and increased size of their polyps.

The results from the SYNAPSE study demonstrated a 57% reduction in the proportion of patients who had surgery in the group treated with mepolizumab versus placebo [HR=0.43 (95% CI 0.25, 0.76)]. Additionally, the proportion of patients who required treatment with a systemic corticosteroid in week 52 of the treatment period was lower in patients who received mepolizumab.

“Patients with chronic rhinosinusitis with nasal polyps experience unpleasant symptoms across a range of severities. As there have been limited treatment options, particularly for those patients with severe disease, they may rely on oral steroids and recurrent surgery to manage their condition,” said Tonya Winders, CEO and president, Allergy and Asthma Network (AAN) and president of Global Allergy and Airways Patient Platform, in the press release. “We welcome the news that mepolizumab will now offer appropriate patients and health care providers a novel treatment option and alternative to surgery.”

GSK announces FDA approval for Nucala (mepolizumab) for use in adults with chronic rhinosinusitis with nasal polyps. GlaxoSmithKline; July 29, 2021. [email]. Accessed July 29, 2021.

Articles

The FDA has approved the monoclonal antibody mepolizumab as a treatment for patients with chronic rhinosinusitis with nasal polyps.

FDA Approves Mepolizumab for Adults With Chronic Rhinosinusitis With Nasal Polyps

The development and operationalization of the workflow within both the clinic and the pharmacy are critical to properly implement a new and novel medication therapy, such as cabotegravir-rilpivirine, for patient initiation and management during treatment, according to a poster presentation at the American Society of Health-System Pharmacists (ASHP) Specialty Pharmacy Conference.

A long-acting monthly intramuscular injection, cabotegravir-rilpivirine was 

 for the treatment of HIV type-1 (HIV-1) and is the first injectable approved by the FDA for the treatment of this disease type. Additionally, the therapy needs to be administered by a health care professional either in the patient’s home or at the clinic.

To appropriately facilitate patient access to this novel therapy, it is necessary to address the specific clinical and operational barriers present. To address these challenges, Yale New Haven Hospital (YNHH) took a pharmacist-led approach in developing a workflow that supports patient education, medication ordering, and administration. Despite being administrative in nature, a streamlined workflow could directly improve patient satisfaction, clinician workload, and the prescription capture rate for the health system’s overall integrated specialty pharmacy, according to the researchers.

At the YNHH Department of Pharmacy Services, officials developed a workflow to efficiently initiate and manage patients on cabotegravir-rilpivirine. Feedback on the rollout of the process was then provided by medical and nursing leadership within the clinics before the workflow structure was fully implemented.

Collaborating directly with the health system’s integrated specialty pharmacy and outside insurance carriers, the embedded ambulatory care pharmacist worked to ensure the medication would be accessible to patients regardless of where the therapy was administered, such as in the clinic through a medical benefit or through prescription insurance coverage for at-home administration.

Additionally, pharmacy administration, the finance team, and information technology team provided the necessary information on the medications for the electronic health record (EHR) to ensure proper billing, ordering, and documentation.

To meet the needs of patients receiving the therapy in both the clinic and at home, 2 workflows were developed that included input from the embedded pharmacist and clinic prescribers so that they could effectively identify patients who were interested in changing their antiretroviral regimen to cabotegravir-rilpivirine.

The newly established workflows sought to address patient education, patient tracking, how medication orders and prescriptions were entered by the ambulatory clinic pharmacist embedded in the clinic, as well as how pre-existing specialty pharmacy services would be used for the new therapy, such as through the use of benefits verification and a medication assistance program.

Furthermore, officials identified areas within the workflow that were in need of technological advancement, such as the process of entering the EHR and computerized physician orders, billing codes, and automated patient reports.

Overall, the new workflow process was designed to ensure clinicians, the embedded pharmacist, and specialty pharmacy team members could collaborate effectively in the tracking of patient progress, patient adherence to monthly injections, and patients’ experience of financial barriers.

In the future, the study authors noted that further assessments would address the success of workflow efficiencies and patient and provider satisfaction, as well as revenue generation for the health system.

Vuernick E, Tong K, Luon S, Stutsky M, Boothe K. Operationalizing a Workflow for In-clinic and Home Administration of Cabotegravir-rilpivirine Monthly Injections for HIV. Poster presented at: 2021 ASHP Specialty Pharmacy Conference; virtual. 

https://www.eventscribe.net/2021/SpecialtyPharmacy/PosterTitles.asp?pfp=BrowsebyTitle

Workflow in the clinic and the pharmacy are critical for the implementation of a new and novel medication therapy, such as cabotegravir-rilpivirine.

Establishing Workflow for In-clinic, Home Administration of Cabotegravir-rilpivirine Injections for HIV-1

Zoster vaccine recombinant, adjuvanted (Shingrix, GlaxoSmithKline) has been approved by the FDA for the prevention of herpes zoster in adults 18 years of age and older who are, or will be, at an increased risk of shingles because of immunodeficiency or immunosuppression. Such an immunocompromised state can occur due to known disease or therapy, leading to individuals in this state being at an increased risk of herpes zoster and associated complications.

A non-live sub-unit vaccine, zoster vaccine recombinant, adjuvanted was previously approved by the FDA in 2017 for the prevention of herpes zoster in adults 50 years of age or older. However, the vaccine is not indicated for the prevention of primary varicella infection, or chickenpox.

Administered intramuscularly in 2 separate doses, the vaccine was previously approved to be administered 2 to 6 months apart among immunocompetent adults. For adults who are, or will be, immunodeficient or immunosuppressed due to known disease or therapy and who would benefit from a shorter vaccination schedule, the FDA approved the administration of the second dose in this patient population 1 to 2 months after the first dose.

Additionally, by expanding the population who can be protected against herpes zoster with the vaccine to those who are immunodeficient or immunosuppressed, this approval expansion makes zoster vaccine recombinant, adjuvanted the first vaccine for use in this patient population.

“We’re proud to offer Shingrix in the US for the prevention of shingles in those who are immunocompromised, with FDA granting a broad indication for use in adults at increased risk of this disease,” said Thomas Breuer, chief medical officer, GSK Vaccines, in a press release. “Older age and being immunocompromised are the most common risk factors for shingles disease. GSK is committed to this important patient population at increased risk for shingles disease and its complications by bringing them a vaccine option that can help prevent this painful condition.”

During clinical studies examining the safety and efficacy of zoster vaccine recombinant, adjuvanted in adults 18 years of age or older, the study investigators evaluated the benefit-risk profile of the vaccine in heterogeneous immunocompromised patient populations who had undergone an autologous hematopoietic stem cell transplant (auHSCT) and in those undergoing treatment for hematological malignancies in a post-hoc analysis.

Additionally, further safety and immunogenicity data were generated in adults who were, or were anticipated to be, immunodeficient or immunosuppressed due to known disease or therapy, such as for patients with HIV, solid tumors, and renal transplants.

“In addition to this new patient population, there are more than 100 million adults 50 years and older in the US already recommended to receive Shingrix,” Breuer said in the press release. “We know many of these individuals missed recommended vaccines during the pandemic and we hope this can be a reminder to them to catch up on all their immunizations, including Shingrix.”

A recent report from Avalere Health found that in total, 17 million doses of recommended vaccines, including zoster vaccine recombinant, adjuvanted, were missed by adults during the pandemic. In light of this increased need for protection against disease among the US population as COVID-19 persists throughout the country, ongoing vaccinations among eligible US adults remains critical.

Shingrix approved in the US for prevention of shingles in immunocompromised adults. Philadelphia, PA: GlaxoSmithKline; July 26, 2021. 

https://us.gsk.com/en-us/media/press-releases/shingrix-approved-in-the-us-for-prevention-of-shingles-in-immunocompromised-adults/

Zoster vaccine recombinant, adjuvanted has been approved by the FDA for the prevention of herpes zoster in adults 18 years of age and older who are, or will be, at an increased risk of shingles because of immunodeficiency or immunosuppression.

FDA Approves Expansion of Shingrix for Prevention of Herpes Zoster in Immunocompromised Adults

Despite the current illegality of most psychedelic drugs at the federal level in the United States, the US government has not always been averse to the exploration and funding of research into the benefits of psychedelic medicine.

Until 1968 when psychedelics such as psilocybin, or mushrooms, and lysergic acid diethylamide (LSD) were made illegal and classified as Schedule I drugs, the government had funded a vast quantity of the research into the potential benefit of these drugs for human health, and specifically, mental health.

In particular, LSD took a primary role in the research conducted throughout the 40s, 50s, and 60s into the potential therapeutic benefit of psychedelic medicine. First developed in 1938 by Swedish chemist Albert Hofmann, LSD was accidentally synthesized by Hoffman in his lab, according to his notes. After this accident, he then proceeded to accidentally ingest it, according to his notes. Following this series of serendipitous events, Hofmann noted the resulting mind-altering effects the drug seemed to induce.

Because Hofmann was conducting this research on behalf of Sandoz Pharmaceuticals, the company was impressed by the properties Hoffman claimed this new drug possessed. Following the drug’s development, Sandoz Pharmaceuticals began to bring it to the attention of other clinical researchers working in the United States in 1949.

However, LSD was not the first psychedelic that researchers in the United States examined to ascertain data as to its therapeutic benefit. In 1947, the US Navy conducted mescaline studies in the hopes of determining its efficacy and value as a truth serum, and US medical researcher Humphry Osmond investigated the molecular similarity between mescaline and human adrenaline around the same time period.

During trials assessing the therapeutic value of LSD for treating mental health disorders, researchers believed it was ethically important for them to first ingest the drug themselves—as was the common practice of the time—before releasing it to the public for consumption. And with LSD, this ethical impulse was no different.

For approximately 15 years following its introduction to medical researchers in the United States, a multitude of psychedelic medical trials were conducted. As a result, psychedelic drugs became freely available among thousands of medical professionals and their colleagues, and, sometimes, close acquaintances.

For much of that time, psychedelics, such as LSD, were believed to act as a psychomimetic, which is a drug that mimics mental illnesses, such as schizophrenia.

 During studies conducted in the early 1950s, researchers used LSD themselves in the belief that it could improve their understanding of the experiences of their mentally ill patients.

Additionally, studies were conducted with volunteers, who were given LSD before being made to take “lengthy psychological and intelligence tests.”The researchers found these tests less fruitful than they had hoped in retrieving information as to the deeper nature of mental illness.

Instead, participants in the study responded in vastly variant ways, as some subjects experienced euphoria whereas others felt anxious, empty, and lonely. This led researchers to assume, for a time, that these experiences were similar to those of patients suffering with mental illnesses, such as schizophrenia.

Despite the few resources available to verify this assumption, this anticipated effect of LSD inducing a state similar to that of schizophrenia was upheld by other researchers in the medical community, and then broadly disseminated to the public.

Occasionally, these assumptions regarding LSD’s ability to induce schizophrenia were validated by some medical professionals’ own personal research in the form of self-administration and certain studies involving small cohorts of volunteers. This assumption went on to support what would lead to a much longer term mistrust of psychedelic medicine within US society more broadly.

However, this mistrust did not dissuade everyone from further investigation into the effects of psychedelic drugs, with researchers such as Sidney Cohen, a clinical professor in pharmacology, who self-administered LSD in 1955. In his notes, he explained that he expected the drug to induce a sensation of paranoia, but he was shocked that what he experienced instead was “the worries and frustrations of everyday life vanished; in their place was a majestic, sunlit, heavenly, inner quietude.”

Based off his experience, Cohen made efforts to redefine taking LSD as allowing for a “shift of consciousness.”1 Other intellectuals of the day, such as author Aldous Huxley, shared Cohen’s perception of drugs such as LSD and mescaline as being able to allow for an altered state of mind that could induce a vision of "how one ought to see, how things really are."

The impact of psychedelics on intellectuals and intellectual thought was not new to those living during the 1950s. Even in the 1880s, philosopher William James wrote of the mystical effects of nitrous oxide and its ability to help him to better understand the writings of Hegel. Not dissuaded by this revelation, James went on to experiment extensively with peyote, the effects of which he published in the 

In the next year after James’ article was published extolling the benefits of peyote, mescaline was successfully isolated.

 Approximately 40 years later, Albert Hoffman would accidentally synthesize LSD, and then another 10 years after that, Hoffman would less accidentally synthesize psilocybin in the 1950s.

By the mid 1960s, more than 40,000 patients had been administered LSD during clinical trials with over 1000 scientific papers published regarding the study findings as to the efficacy and safety of the drug.

 Despite these efforts and several international conferences held regarding the effects of psychedelic medicine and its impact as a treatment in the field of psychiatry, by the late 1960s, negative associations with psychedelic medicine persisted within the social consciousness of the United States. Eventually, these public attitudes led to their criminalization in 1968. With this criminalization, all federal funding for further research was eliminated, and psychedelic drugs such as LSD and psilocybin were classified as Schedule I drugs, which establishes them on a federal level as having no accepted medical use and a high risk for potential abuse.

Currently, following the COVID-19 pandemic and the resulting catastrophic rise in mental health issues, psychedelic medicines such as psilocybin, MDMA, ketamine, and cannabis are finding a new place in the field of medical research. In many ways, the desperate need of today may call for desperate measures for tomorrow, with renewed hope for finding new medicines to treat the needs of a growing number of patients who are living and suffering from mental illness.

DiPaolo M. LSD and The Hippies: A Focused Analysis of Criminalization and Persecution in The Sixties. 

http://pitjournal.unc.edu/content/lsd-and-hippies-focused-analysis-criminalization-and-persecution-sixties

MAPS. The Medical History of Psychedelic Drugs. MAPS website. 

https://maps.org/images/pdf/history_of_psychedelics.pdf

Trials assessing psychedelic medicine were conducted in the United States for several decades before they were criminalized in 1968, with government and military funding provided for research in the field.

Pharmacy Fact: Clinical Research into Psychedelic Medicine Flourished for Decades Before Criminalization

The FDA has approved pembrolizumab (Keytruda, Merck) in combination with lenvatinib (Lenvima, Eisai) for the treatment of advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). Additionally, the combination therapy is specifically approved for patients who have experienced disease progression following prior systemic therapy in any setting, but who are not candidates for curative surgery or radiation.

After being granted accelerated approval for advanced endometrial carcinoma on September 17, 2019, the combination therapy was granted priority review and received breakthrough therapy designation for this indication. In the FDA’s review process, officials assessed data from the Study 309/KEYNOTE-775 trial to confirm the clinical benefit of an accelerated approval.

The Study 309/KEYNOTE-775 trial was multicenter, open-label, randomized, and active-controlled, with investigators enrolling 827 patients with advanced endometrial carcinoma who were previously treated with at least 1 prior platinum-based chemotherapy regimen in any setting, including neoadjuvant and adjuvant treatments.

During the study, patients were randomized 1 to 1 into a cohort administered pembrolizumab 200 mg intravenously every 3 weeks with lenvatinib 20 mg orally once daily or into a group administered the investigator’s choice of either doxorubicin or paclitaxel.

In the blinded independent central review’s (BICR’s) analysis of the study data, the major efficacy outcome measures were progression-free survival (PFS) and overall survival (OS). Additional efficacy outcome measures assessed by the BICR included the objective response rate (ORR) and duration of response (DOR).

The data compiled during the trial demonstrated that patients in the pembrolizumab and lenvatinib group with advanced endometrial cancer that is not MSI-H or dMMR had a median PFS of 6.6 months (95% CI: 5.6, 7.4), whereas patients given the investigator’s choice treatment had a PFS of 3.8 months (95% CI: 3.6, 5.0).

Additionally, the investigators observed that the median OS for patients in the pembrolizumab and lenvatinib group was 17.4 months (95% CI: 14.2, 19.9) and for the investigator’s choice treatment it was 12.0 months (95% CI: 10.8, 13.3). The investigators also found that the ORR was 30% (95% CI: 26, 36) and 15% (95% CI: 12, 19), with a median DOR of 9.2 months (1.6+, 23.7+) and 5.7 months (0.0+, 24.2+), respectively (p<0.0001).

For patients being treated with pembrolizumab in combination with lenvatinib, the most frequent adverse events reported in ≥ 20% of patients were hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight loss, abdominal pain, urinary tract infection, proteinuria, constipation, headache, hemorrhagic events, palmar-plantar erythrodysesthesia, dysphonia, and rash.

Based on the data and the findings of the study, the recommended dose of pembrolizumab for endometrial carcinoma is 200 mg every 3 weeks. However, with lenvatinib 20 mg orally once daily, the recommended dose of pembrolizumab is 400 mg every 6 weeks.

FDA. FDA grants regular approval to pembrolizumab and lenvatinib for advanced endometrial carcinoma. FDA website. 

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-regular-approval-pembrolizumab-and-lenvatinib-advanced-endometrial-carcinoma?utm_medium=email&utm_source=govdelivery

The FDA has approved pembrolizumab in combination with lenvatinib for the treatment of advanced endometrial carcinoma that is not microsatellite instability-high or mismatch repair deficient 

FDA Approves Pembrolizumab, Lenvatinib Combination Therapy for Advanced Endometrial Carcinoma

The FDA has approved the first and only intravenous immunoglobulin (IVIg) (Octagam, Octapharma USA) indicated for use in adults with dermatomyositis. A rare immune-mediated inflammatory disease, dermatomyositis is an idiopathic autoimmune disorder of unknown cause that affects the lives of approximately 10 out of every 1 million US residents.

The FDA approval was based on the results from the randomized, prospective, double-blind, placebo-controlled ProDERM phase 3 clinical trial, which was conducted among 95 patients across 19 international sites and 17 sites in the United States. This trial is the first to evaluate the long-term efficacy and safety of IVIg in adults with dermatomyositis and is the largest to assess IVIg as a treatment option for dermatomyositis.

“The ProDERM study will have a significant impact on clinical practice because IVIg is likely to become an important treatment option for patients with dermatomyositis,” said Rohit Aggarwal, MD, MS, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh School of Medicine and a member of the ProDERM study steering committee, in a press release. “The study gives clinicians much more confidence in the efficacy and safety of intravenous immunoglobulin and provides valuable information about what type of patient is best suited for the treatment.”

Patients with dermatomyositis commonly experience skin rashes, chronic muscle inflammation, and progressive muscle weakness. These symptoms most frequently affect adults in their late 40s to early 60s and children aged 5 to 15 years.

With these symptoms, complications can occur such as difficulty swallowing, aspiration pneumonia, breathing problems, and calcium deposits on muscles, skin, and connective tissues. In light of these complications, patients with dermatomyositis have more than a 3 times increased mortality risk in comparison with the general population of the same age.

“The FDA approval of Octagam® 10% as a safe and effective treatment for dermatomyositis in adults is exciting news for patients who previously relied on unapproved treatments,” said Octapharma US President Flemming Nielsen, in the press release. "Octapharma is committed to providing life-saving and life-enhancing therapies for patients with rare diseases. We look forward to partnering with patient organizations and the medical community to develop educational and other support programs that will serve dermatomyositis patients.”

The IVIg treatment is a liquid preparation that is also indicated for chronic immune thrombocytopenic purpura in adults, as well as for dermatomyositis in adults.

FDA Approves Octapharma’s Octagam® 10% for Adult Dermatomyositis. Paramus, NJ: Octapharma USA; July 20, 2021. [email] Accessed July 21, 2021.

The FDA has approved the first and only intravenous immunoglobulin indicated for use in adults with dermatomyositis.