Skylar Kenney, Assistant Editor

Prescribing generic medications rather than brand-name medications to treat blood vessel and heart diseases in Medicare Part D could save more than $600 million each year in the United States, according to a study published in Circulation: Cardiovascular Quality and Outcomes. “Research shows that when passed on to patients, high prices reduce medication adherence and can lead to negative health outcomes,” said Elliott Marshall Antman, MD, FAHA, former president of the American Heart Association (AHA), chair of the writing group for the AHA’s 2017 presidential advisory on medication access and affordability, and senior physician specializing in cardiovascular medicine at Brigham and Women’s Hospital in Boston, Massachusetts, in a statement. “Patients’ health suffers when they can’t afford the medicines they need.”

To conduct the study, investigators gathered data on prescription-filling patterns, comparing brand-name medications that prevent or treat blood clotting, high cholesterol, high blood pressure, and irregular heart rhythms with their generic counterparts. Using records from Medicare Part D prescription coverage, which applies to all adults older than 65 years in the United States, the study authors reviewed prescriptions filled in 2017 for cardiovascular medications that are available both as brand-name and generic formulas. Medicare Part D paid nearly $23 billion for cardiovascular medication prescriptions in 2017, with $11 billion of that spending put toward medications available in both brand-name and generic formulas, according to the results of the study.

Although just 2.4% of prescriptions filled were for brandname medications, they accounted for more than 21% of total Medicare Part D prescription spending. Furthermore, 8.2% of the prescribing physicians reviewed in the study who prescribed generics the least could potentially account for 50% of the available cost savings estimated by the investigators.

After controlling for cash rebates available for some of the brand-name medications with available generic formulations, the investigators estimated that increased use of generic substitutions in Medicare Part D could save $641 million per year. This includes approximately $135 million in out-of-pocket cost savings to patients. “Increasing the use of generic medications would decrease patient out-of-pocket costs and make medications more affordable, which may, in turn, improve adherence rates and reduce the financial burden of medication therapy,” the senior author Alexander Tarlochan Singh Sandhu, MD, MS, instructor of medicine at Stanford University School of Medicine in California, said in a statement.

In certain states, laws require pharmacists to seek patient consent before substituting with a generic. Other state laws mandate that pharmacists substitute a generic unless it is indicated by the physician that the prescription must be dispensed as written. “Generic substitutions have similar efficacy as brand-name options. However, there may be misinformation and hesitation about the safety and efficacy of generics,” Sandhu said.

“FDA regulatory oversight into the safety and efficacy of generic substitutions is critical for improving the use of generic medications. Ensuring patients almost always receive the generic option will further reduce patient out-of-pocket costs,” Sandhu said. “Health care systems should continue to find ways to encourage clinicians and patients toward generic medication options when available.”

The investigators listed multiple limitations to the study results. Only Medicare Part D prescription coverage was reviewed, which includes only adults 65 years or older. Additionally, the study did not account for dosage differences, and it included generic substitutions even if they were more expensive than the brand-name formulation with cash rebates considered.

The 2017 presidential advisory on medication access and affordability from the AHA states that the costs of medications should be readily available for patients and practitioners so they can make informed treatment decisions. Tools that detail information on the pricing and value of medications would help both health care professionals and patients make decisions in selecting care regimens that best align with patient and family goals and preferences, according to the advisory.

Use of generic heart meds in Medicare Part D could save more than $600 million a year. News release. American Heart Association; December 9, 2021. Accessed December 15, 2021. https://www.eurekalert.org/news-releases/937003

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New analysis shows the substitution would cut costs by $600 million in the United States annually.

Replacing Brand-Name Cardiovascular Drugs Could Save Patients Money

®, experts in the field examined multiple aspects of Waldenström macroglobulinemia (WM), including how it presents, what pharmacists should know about the disease, and how to treat it.

WM is an uncommon lymphoma, with approximately 3000 new cases reported each year in the United States.

 According to Steven P. Treon, MD, PhD, director of the Bing Center for Waldenström’s Macroglobulinemia, an attending physician for medical oncology at Dana- Farber Cancer Institute and Brigham and Women’s Hospital, and an associate professor of medicine at Harvard Medical School in Boston, Massachusetts, the disease shares features of both lymphoma and myeloma.

“As a result, the therapies that we typically use are meant to cover the clone that transcends both mature B cells and plasma cells,” Treon said during the discussion. “And so classically with chemoimmunotherapy, we’ve had to combine drug therapy that goes after lymphoma along with drug therapy that goes after myeloma so we can cover the entire clone.”

Treon also noted that WM can present several ways, with hyperviscosity syndrome being a common manifestation for patients.

“[WM] can have the IgM antibody made by tumor cells acting as autoantibodies,” Treon said. “[It] can [cause] renal failure because of the deposition of those antibodies, as well as amyloidosis. [WM] can present with classical cytopenias, and [it] can also present with bulky masses and even disease that gets into the [central nervous system (CNS)] space.”

For this reason, Treon explained, it is important to keep in mind from the pharmacy perspective that there can be multicompartment disease.

“Sometimes even the dosimetry of some of the therapies that we use, and even the therapies themselves, can be very much affected by what compartment we’re looking to treat,” he said.

Additionally, the panel discussed methods of identifying the disease. They noted that although the 

mutation is carried by 95% to 97% of patients with WM, it is not unique to the disease because a small percentage of patients with marginal zone lymphoma also present with the mutation.

 Further, it is extremely common for individuals with primary CNS lymphoma to harbor a 

“What’s fairly unique to [WM] is [the] IgM protein because the IgM that’s made by the tumor cells can mediate a lot of the morbidity,” Treon said. “And as a result, when you’re thinking about therapy, you want to think about ways that you can actually turn that IgM off—how you can target the tumor cells in a way that you can get that IgM down and, many times, get it down very rapidly, especially with somebody with hyperviscosity syndrome.”

According to Treon, approximately 30% of patients with WM do not require immediate treatment. If a patient with WM is feeling well and has no symptoms of clinical significance, he said health care professionals can “watch and wait” before initiating any treatment. Guidelines from the National Comprehensive Cancer Network define points at which providers should shift to active treatment.

“It is important to recognize that a fair number of patients...meet the diagnostic criteria but are relatively asymptomatic,” Treon said during the discussion. “We tend to treat people who have very high IgM levels. If they’re above 6000 mg/dL, we’ll treat them because the data that we have when we’ve published seem to suggest that they’re more likely to get into trouble than not, and, therefore, why wait until somebody gets into trouble? Because the manifestations of hyperviscosity sometimes are irreversible, like bleeding in the retina.”

1. IMBRUVICA® (ibrutinib) in Combination with Rituximab Showed Greater Efficacy Compared to Placebo Plus Rituximab in Patients with Waldenström’s Macroglobulinemia, a Rare and Incurable Form of Non-Hodgkin’s Lymphoma. Chicago, IL: Janssen Pharmaceutical Companies; June 1, 2018. Accessed January 10, 2022. 

https://www.jnj.com/media-center/press-releases/imbruvica-ibrutinib-in-combination-with-rituximab-showed-greater-efficacy-compared-to-placebo-plus-rituximab-in-patients-with-waldenstroms-macroglobulinemia-a-rare-and-incurable-form-of-non-hodgkins-lymphoma

2. Gachard N, Parrens M, Soubeyran I, et al. IGHV gene features and MYD88 L265P mutation separate the three marginal zone lymphoma entities and Waldenström macroglobulinemia/lymphoplasmacytic lymphomas. 

 27,183–189(2013). doi: 10.1038/leu.2012.257

The uncommon disease shares features of both lymphoma and myeloma.

Waldenström Macroglobulinemia: Common Presentations, Treatment Strategies

A pilot program evaluating remote patient monitoring (RPM) for patients with cancer who were either persons under investigation (PUI) for COVID-19 infections or COVID-19 positive with mild or no symptoms found that participants effectively engaged with the program’s data reporting system at least once a day 97.2% of the time, according to a presentation at the Association of Community Cancer Centers 38th National Oncology Conference.

The RPM pilot program, conducted at Inova Health System, enrolled 26 patients who were educated on program parameters by advanced practice providers (APPs) and provided with RPM packages. These packages contained an automatic blood pressure cuff, an oral thermometer, a finger pulse oximeter, and a configured iPad to enter vital results.

Participants were asked to conduct a vital sign assessment 3 times per day, recording temperature, heart rate, blood pressure, and oxygen saturation. They were also asked to conduct a self-assessment the same number of times, which asked participants if they felt better, worse, or the same as the previous day, as well as whether they were experiencing shortness of breath.

Participants were also given access to a password-protected patient dashboard, monitored by APPs 12 hours a day, 7 days a week. If a participant recorded an issue during nighttime hours, they were directed to an on-call provider. Patients who reported shortness of breath prompted an alert in the system, and patients were called once a day for a check-in with an APP regardless of clinical status.

“If the APP saw any data [in the dashboard] that concerned them, they would call the patients and bring them into our COVID-19 clinic to get them evaluated,” said Nancy Bowles, MHA, BSN, RN, OCN, CRNI, NEA-BC, CPC, CHONC, vice president of nursing at Inova Schar Cancer Institute in Fairfax, Virginia, during the presentation. “We could do some IV [intravenous] therapy there—a lot of hydration, blood products, things like that—and treat the patients and try to keep them out of the hospital.”

According to the investigators, the program saw high overall compliance and engagement, with patients entering data at least 1 time per day 97.2% of the time and entering data all 3 times 65.7% of the time.

“Twenty-three [patients] were monitored at home without requiring hospitalization,” Bowles said. “This is 88% of our patients. Two patients were admitted for non–COVID-19–related issues. One patient was admitted with an upper respiratory infection and ended up testing negative for COVID-19 twice and recovered with antibiotics.”

The program duration was based upon the needs of participants. PUIs remained in the program until either their COVID-19 test results came back negative or the patient was no longer symptomatic. Patients who tested positive for COVID-19 remained in the program until they received 2 negative COVID-19 tests 24 hours apart and were no longer symptomatic.

The presenters listed several limitations of the program, including language interpretation, technological literacy, a lack of electronic medical record integration, and reimbursement challenges.

“For our iPads, we were only able to have those in English and Spanish, although we did have patients that could potentially have benefited from additional languages as well,” said Laura Matthews, MBA, MPH, vice president and administrator at Inova Schar Cancer Institute, during the presentation. “[A]s we think about the use of RPM, [we need to make] sure that we have that availability of enough translation and enough languages to make this helpful for our patients.”

Looking to the future, the presenters anticipate that RPM may be used for outpatients with low-risk febrile neutropenia, patients with leukemia during consolidation treatments, and tracking vitals, weight, and calorie counts for patients in chemoradiation.

“Having on-demand access to patient information for these patients, it’s incredible,” Matthews said. “I think the sky is the limit in terms of the number of ways that we can continue to use remote patient monitoring over time.”

Matthews L, Bowles N. Remote monitoring of patients with cancer during COVID-19. Presented at: Association of Community Cancer Centers 38th National Oncology Conference; November 9-10, 2021; virtual.

The results of a pilot program investigating the efficacy of remote patient monitoring for patients with cancer showed that it helped to keep high-risk individuals out of the hospital.

RPM Is Effective for Patients With Cancer During the Pandemic

The FDA has granted abbreviated new drug application (ANDA) approval to Milla Pharmaceuticals, a subsidiary of the Alter Pharma Group, for its generic version of magnesium sulfate in water for injection in nonpolyvinyl chloride, single-patient use containers.

Approved dosages include 2 g/50 mL (40 mg/mL), 4 g/100 mL (40 mg/mL), and 4 g/50 mL (80 mg/mL). Magnesium sulfate injection is included on the American Society of Health-System Pharmacists’ (ASHP) drug shortage list of essential medications, and the approval of this generic injection could help with supply issues in the United States.

Magnesium sulfate injection is indicated for the prevention of seizures in patients with preeclampsia, as well as seizure control in patients with eclampsia, a potentially life-threatening pregnancy complication. The drug effectively controls and prevents eclampsia convulsions without causing depression of the central nervous system for either the baby or the mother, according to Milla.

This is the second ANDA approval granted to Milla in 2021. In July, the FDA granted ANDA approval to the company’s generic sodium acetate injection 2 MEQ/mL, which the agency had placed on its drug shortages list. Intravenous (IV) sodium acetate is indicated as a sodium source for addition to large-volume IV fluids to correct or prevent hyponatremia in patients with restricted or no oral intake. The drug also functions as an additive for preparing specific IV fluid formulas when the needs of the patient cannot be met by standard electrolytes or nutrient solutions.

“Not only are we extremely proud that, after the launch of our generic injectable acetaminophen (paracetamol IV) in December 2020 and of our generic version of sodium acetate injection in July 2021, we are now lining up our third launch in the United States in such a short period of time,” Filip Van de Vliet, CEO of the Alter Pharma Group, said in a statement.

“We are also putting into action our ambition to make affordable medicines available to all and to address critical drug shortages, whether they are in the European Union or the United States,” he said. “Magnesium sulfate injection is another example of a product in shortage in the US market for which we can offer a high-quality generic equivalent to the patients in need.”

There are many drug shortages directly influenced by the COVID-19 pandemic. A combination of anticipatory purchasing and factory shutdowns in response to the health crisis has led to disruption of the pharmacy supply chain and subsequent shortages.

 The ASHP and FDA shortage lists each contain nearly 200 drugs.

Investigators have noted that there are multiple causes for drug shortages, which include discontinuation of drugs from the market, inadequate quantities of raw materials, and issues with legislation, manufacturing, or procurement. They suggested that, because of the pandemic’s effect on the supply chain, policymakers establish a stepwise transition process for patients to switch to generic versions of drugs that can be manufactured nationally,

1. Milla Pharmaceuticals Inc. announces approval of a generic version of magnesium sulfate in water for injection, in non-PVC, single-patient use containers. News release. Milla Pharmaceuticals Inc. November 9, 2021. Accessed November 11, 2021. https://www.businesswire.com/news/ home/20211109005804/en/Milla-Pharmaceuticals-Inc-Announces-Approval-of-a-Generic-Version-of-Magnesium-Sulfate-in-Water-for-Injection-in-Non-PVC-Single-Patient-Use-Containers

2. Milla Pharmaceuticals announces approval and launch of a generic version of sodium acetate injection 2MEQ/mL by Pfizer Inc. News release. Milla Pharmaceuticals Inc. August 26, 2021. Accessed November 11, 2021. https://www.businesswire.com/news/home/20210826005694/en/Milla- Pharmaceuticals-Announces-Approval-and-Launch-of-a-Generic-Version-of-Sodium-Acetate-Injection-2MEQmL-by-Pfizer-Inc

3. Bookwalter CM. Drug shortages amid the COVID-19 pandemic. U.S. Pharmacist. February 12, 2021. Accessed November 11, 2021. https://www. uspharmacist.com/article/drug-shortages-amid-the-covid19-pandemic

4. Drug shortages list. American Society of Health-System Pharmacists. Accessed November 29, 2021. https://www.ashp.org/drug-shortages/current-shortages/drug-shortages-list?page=CurrentShortages&sort=1

5. FDA drug shortages. FDA. Accessed November 11, 2021. https://www. accessdata.fda.gov/scripts/drugshortages/default.cfm

6. Badreldin HA, Atallah B. Global drug shortages due to COVID-19: impact on patient care and mitigation strategies. Res Social Adm Pharm. 2021;17(1):1946-1949. doi:10.1016/j.sapharm.2020.05.017

Agency green light could help get medication off ASHP drug shortage list by reducing supply issues.

FDA Approves Magnesium Sulfate Injection From Milla Pharmaceuticals

Intranasal vaccination may provide broad-based protection against heterologous respiratory viruses based on early results in mice, whereas injection-based vaccination did not have the same effect, according to a study published in 

Mucus membranes have a unique defense system for combatting airborne or foodborne pathogens. Immune B cells secrete immunoglobin A (IgA) antibodies, which work locally on mucosal surfaces in the nose, stomach, and lungs. The investigators sought to establish whether triggering IgA response might also produce a localized immune response against respiratory viruses.

“The best immune defense happens at the gate, guarding against viruses trying to enter,” said Akiko Iwasaki, PhD, the Waldemar Von Zedtwitz Professor of Immunobiology at Yale, in a press release

To conduct the study, investigators tested a protein-based vaccine designed to jump start an IgA immune response. This vaccine was administered to mice, either intramuscularly or intranasally.

These mice were then exposed to multiple strains of influenza viruses. According to the investigators, the mice that received intranasal vaccination were significantly better protected against respiratory influenza than those who received injections.

Further, these nasal vaccines induced antibodies that protected the mice against a variety of flu strains, not just against the strain the vaccine was meant to protect against. This was not observed in the population that received the vaccine through a shot.

Currently, the investigators are testing nasal vaccine strains against COVID-19 in animal models. Although both the vaccine injections and nasal vaccines increased levels of antibodies in the blood of the mice, only the nasal vaccine enabled IgA secretion into the lungs.

If these nasal vaccines are proven safe and efficient in humans, the investigators said they expect them to be used in conjunction with existing vaccines and boosters that work system wide. This method would allow the body to add immune system support at the source of infection, according to the study.

Nasal vaccine may aid fight against new viral variants [news release]. EurekAlert; December 10, 2021. Accessed December 13, 2021. 

https://www.eurekalert.org/news-releases/937314

Immune B cells secrete immunoglobin A antibodies that work on mucosal surfaces in the nose, stomach, and lungs.

Nasal Vaccines May Provide Additional Immune Support Against Respiratory Viruses

Certain group 3 innate lymphoid cells (ILC3s)—immune cells that typically protect against gastrointestinal inflammation—may have the opposite effect in multiple sclerosis (MS) and other brain inflammation-related conditions, according to a study published in 

. The investigators said these results suggest that inhibiting the activity of these cells could serve as a new therapeutic approach for neurologic conditions.

While studying ILC3s in a mouse model of MS, the investigators discovered a unique subset of ILC3s that circulate in the bloodstream and can enter the brain. These ILC3s—named inflammatory ILC3s—caused T cells to attack myelinated nerve fibers, leading to MS-like disease symptoms. Similar inflammatory ILC3s were found in the peripheral blood and cerebrospinal fluid of MS patients.

“This work has the potential to inform our understanding of, and potential treatments for, a broad variety of conditions involving T-cell infiltration of the brain,” said Gregory Sonnenberg, PhD, associate professor of microbiology and immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine, in a press release.

According to the investigators, inflammatory ILC3s present bits of myelin protein—the primary component of the insulating layer around nerve fibers—to T cells. This prompts the T cells to attack myelin and cause the nerve damage that gives rise to disease signs. By removing MHCII from the inflammatory ILC3s, a key component normally used in the antigen-presenting process, the investigators were able to block the cells’ ability to activate myelin-attacking T cells.

“Despite our very best disease-modifying therapies for MS, patients continue to progress, and since disease onset is early in life, they face the prospect of permanent physical and cognitive disability,” said Tim Vartanian, MD, PhD, professor of neuroscience in the Feil Family Brain and Mind Institute at Weill Cornell Medicine, chief of the division of multiple sclerosis and neuro-immunology and a professor of neurology in the Department of Neurology at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center, in the release. “Identification of inflammatory ILC3s with antigen presentation capabilities in the central nervous system of people with MS offers a new strategic target to prevent nervous system injury.”

The investigators also found that they were able to effectively program ILC3s in other tissues to counter the activity of brain-infiltrating T cells, which prevented the MS-like condition in mice. They said that this study points to the possibility that MS and potentially many other inflammatory conditions could be treated by directly inhibiting the activity of inflammatory ILC3s that infiltrate the brain or by targeting self-antigens to the intestinal ILC3s that promote tolerance in other tissues.

Novel immune cell population may trigger inflammation in multiple sclerosis and other brain disorders [news release]. EurekAlert; December 1, 2021. Accessed December 3, 2021. 

https://www.eurekalert.org/news-releases/936550

Inhibiting the activity of group 3 innate lymphoid cells could serve as a new therapeutic approach for neurologic conditions.