Lauren Biscaldi is the Managing Editor of Drug Topics. 

Lauren Biscaldi, Managing Editor

Adalimumab-atto (Amjevita), the first FDA approved adalimumab (Humira) biosimilar, is now available in the United States, according to a press release from manufacturer Amgen.

According to the 2016 FDA approval announcement, adalimumab-atto is approved to treat moderately to severely active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderately to severely active Crohn disease, moderately to severely active ulcerative colitis, and moderate to severe plaque psoriasis in adults.

 The medication is also approved for treatment of moderately to severely active polyarticular juvenile idiopathic arthritis in pediatric patients aged 4 years and older.

At the time of its approval, adalimumab-atto was the fourth biosimilar medication approved by the FDA. The approval was based on an evidence review including the structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamic data, clinical immunogenicity data, and other clinical safety and effectiveness data.

Adalimumab-atto 40 mg is available at 2 prices: $3288 and $1557 for a 2-week supply of medication—a discount of 5% and 55%, respectively, compared with adalimumab.

 According to Amgen, the company’s goal “is to provide broad access for patients by offering 2 options to health plans and pharmacy benefit managers.”

“Biosimilars are extensively studied, FDA-approved treatments that have the potential to reduce costs to the health care system,” said Steven Taylor, president and CEO at the Arthritis Foundation. “[Adalimumab-atto] provides another treatment option for patients and their doctors.”

Several other adalimumab biosimilars are set to launch in the United States in July.

1. Amjevita (adalimumab-atto), first biosimilar to humira, now available in the United States. News release. Amgen. January 31, 2023. Accessed January 31, 2023. https://www.amgen.com/newsroom/press-releases/2023/01/amjevita-adalimumabatto-first-biosimilar-to-humira-now-available-in-the-united-states

2. FDA approves Amjevita, a biosimilar to Humira. News release. FDA. September 23, 2016. Accessed January 31, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-amjevita-biosimilar-humira

3. Mandowara K. Amgen launches biosimilar version of AbbVie’s Humira. Reuters. Published January 31, 2023. Accessed January 31, 2023. https://www.reuters.com/business/healthcare-pharmaceuticals/amgen-launches-biosimilar-version-abbvies-humira-2023-01-31/

Articles

Adalimumab-atto was first approved by the FDA in 2016.

First Adalimumab Biosimilar Launches in US Market

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) has unanimously voted to recommend replacing the previously authorized COVID-19 vaccination regimen with the bivalent version of the vaccine for those who are receiving a primary COVID-19 vaccine.

The FDA is expected to sign off on the VRBPAC recommendation, according to several news sources. Both the FDA and CDC must adopt this recommendation before implementation.

This change in vaccination guidance makes the COVID-19 vaccines more akin to a yearly flu shot, a “major shift in strategy despite a long list of questions about how to best protect against a still rapidly mutating virus,” noted the Associated Press.

The bivalent vaccine, reformulated by both Pfizer-BioNTech and Moderna, protects against the BA.4 and BA.5 Omicron subvariants. More recent evidence indicates that this bivalent formulation also protects against death and severe disease associated with the XBB.1 variant currently dominating cases in the United States.

Vaccine manufacturer Novavax also participated in the VRBPAC meeting, during which the company shared data demonstrating that their COVID-19 vaccine, adjuvanted (NVX-CoV2372)—currently available under an FDA emergency use authorization in individuals aged 12 and older—when used as a booster "induces a broad functional immune response, including against forward drift variants."

 The company is prepared to deliver an updated vaccine to reflect the new FDA guidance. 

 the VRBPAC vote is one part of a larger FDA plan to both simplify and improve the way COVID-19 vaccines are administered. A proposed plan would convene VRBPAC advisers yearly to evaluate whether the COVID-19 vaccine should be updated to reflect currently circulating viral strains.

For most Americans, the FDA noted, a once-yearly COVID booster should be sufficient. However, additional questions around young children and immunocompromised adults were raised—and must be answered with more data.

This story will be updated as it continues to develop.

Foley KE. Change to COVID vaccine formulation signals start of FDA pivot in immunization strategy. 

Published January 26, 2023. Accessed January 27, 2023. 

https://www.politico.com/news/2023/01/26/fda-advisers-annual-covid-immunizations-00079749

Neergaard L. FDA’s advisors back plan to simplify COVID-19 vaccinations. Published January 26, 2023. Accessed January 27, 2023. 

https://apnews.com/article/health-immunizations-us-food-and-drug-administration-business-covid-6fe66fb4b7c9ac6568fb055544b13e20

Novavax announces plan to deliver updated protein-based vaccine consistent with FDA recommendations for 2023/2024 vaccination season at VRBPAC meeting. News release; Novavax. January 27, 2023. Accessed January 27, 2023. 

https://ir.novavax.com/Novavax-Announces-Plan-to-Deliver-Updated-Protein-based-Vaccine-Consistent-with-FDA-Recommendations-for-2023-2024-Vaccination-Season-at-VRBPAC-Meeting

Goodman B. FDA vaccine advisers vote to harmonize COVID-19 vaccines in the United States. 

https://www.cnn.com/2023/01/26/health/fda-covid-19-vaccine-future/index.html

Recommendations from the unanimous vote must be adopted by the FDA and CDC. 

Breaking: FDA Committee Votes in Favor of New, Unified COVID-19 Vaccine Strategy

Women are more likely than men to be affected by Long COVID, according to the results of an analysis published in JAMA.

Given the relative recency with which COVID-19 developed, there is a lack of data surrounding Long COVID, the cluster of varying symptoms that some individuals experience after the acute phase of a SARS-CoV-2 infection. Researchers, therefore, set out to determine the proportion of men and women, both younger and older than 20 years of age, who experienced Long COVID symptoms in either 2020 or 2021, as well as evaluate their symptom severity and expected Long COVID symptom duration.

Investigators utilized data from 54 studies and 2 medical record databases inclusive of individuals across 22 countires who had symptomatic COVID-19. Participant data came from 44 published studies, 10 collaborating cohort studies, and 2 US electronic medical record databases.

The primary study outcome was the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters—persistent fatigue with bodily pain or mood swings, cognitive problems, or ongoing respiratory problems—for 3 months after COVID-19 infection.

The total cohort included 1.2 million individuals (mean age, 4-66 years; 26%-88% men). Results of modeled estimates showed that 6.2% of individuals who had symptomatic COVID-19 experienced at least 1 of the 3 Long COVID symptom clusters during the study period (95% uncertainty interval [UI], 2.4%-13.3%); 3.2% experienced persistitent fatigue with bodily pain and mood swings; 3.7% experienced ongoing respiratory problems; and 2.2% expericned cognitive problems—after adjusting for health status before COVID-19 infection. Ultimately, these comprised of an estimated 51%, 60.4%, and 35.4% of Long COVID cases.

Symptom clusters were more common in women older than 20 years of age than in men of the same age (10.6% vs 5.4%% 3 months after symptomatic COVID-19 infection. Across both sexes, individuals younger than age 20 were affected by Long COVID in approximately 2.8% of symptomatic COVID-19 cases.

Estimated mean duration of a Long COVID symptom cluster was 9 months (95% UI, 7-12 months) among individuals who were hospitalized, and 4 months (95% UI, 3.6-4.6 months) among those who were not. An estimated 15.1% continued experiencing symptoms at 12 months.

Study limitations include the wide 95% UI estimates, indicative of “limited and heterogenous data,” the need for multiple algorithms to achieve consistency, and assumptions about the similarity of the course of Long COVID across countries, among other limitations.

“The pattern of Long COVID symptoms by sex is distinct from that of severe acute SARS-CoV-2 infection, which tends to affect more males,” the researchers wrote. “This difference suggests that the underlying mechanism of Long COVID may be different from that of the severity of acute SARS-CoV-2 infection.”

1. Global Burden of Disease Long COVID Collaborators. Estimated global proportions of individuals with persistent fatigue, cognitive, and respiratory symptom clusters following symptomatic COVID-19 in 2020 and 2021. JAMA. 2022;328(16):1604-1615. doi: 10.1001/jama.2022.18931

Investigators analyzed the proportion of individuals with 1 of 3 clusters of Long COVID symptoms.

Examining the Global Burden of Long COVID by Sex

The FDA has approved bexagliflozin (Brenzavvy), a once-daily, oral, sodium-glucose cotransporter 2 (SGLT2) inhibitor as an adjunct therapy to diet and exercise for the improvement of glycemic control in adults with type 2 diabetes, according to a news release.

According to manufacturer TheracosBio, the FDA approval is based on results of a clinical program evaluating the safety and efficacy of bexagliflozin in 23 clinical trials and a cohort of more than 5000 adults with type 2 diabetes. Phase 3 study results in particular showed that bexaglifloxin significantly reduced both hemoglobin A1c (HbA

) and fasting blood sugar after 24 weeks, regardless of administration as a monotherapy, in combination with metformin, or as an add-on to standard of care treatment regimens. Modest decreases in both weight and systolic blood pressure were also noted, although bexagliflozin is not approved for either weight or blood pressure reduction, per the press release.

“As a class of drugs, SGLT2 inhibitors have shown tremendous benefit in treating adults with type 2 diabetes,” said Mason Freeman, MD, director of the translational research center at Massachusetts General Hospital in Boston. “I am greatly impressed with the efficacy of the drug in reducing blood glucose levels and I believe it is an important addition to the SGLT2 inhibitor class of drugs.”

Bexagliflozin is not indicated for the treatment of type 2 diabetes in patients with end stage renal disease, or in patients who are receiving dialysis. Treatment can be initiated in adults with type 2 diabetes who have an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73m

TheracosBio announces FDA approval of Brenzavvy (bexagliflozin) for the treatment of adults with type 2 diabetes. News release. TheracosBio. January 23, 2022. Accessed January 23, 2023. 

https://theracosbio.com/wp-content/uploads/2023/01/01-23-2023_TheracosBio-Announces-FDA-Approval-of-Brenzavvy.pdf

The new medication reduces HbA1c and improves glycemic control as an adjunct to diet and exercise. 

Bexagliflozin Approval Creates New SGLT2 Inhibitor Option for Adults With T2D

The Drug Enforcement Administration (DEA) has joined the Director of the White House Office of National Drug Control Policy and multiple health care associations, including the American Society of Health-System Pharmacists (ASHP), in applauding the elimination of the DATA-Waiver or X-Waiver program.

 The repeal became law when President Joe Biden signed the Consolidated Appropriations Act, 2023 (CAA 2023) into law on December 29, 2022.

The move comes at a time when the number of Americans living with substance use disorder continues to soar: a total of 110,236 people died due to an overdose during a 12-month period, according to CDC data reported by NPR on December 31, 2022.

Section 1262 of the bipartisan Omnibus bill “removes the federal requirement for practitioners to submit a Notice of Intent (have a waiver) to prescribe medications, like buprenorphine, for the treatment of opioid use disorder (OUD),” according to an update posted by the Substance Abuse and Mental Health Services Administration (SAMHSA).

The law also removes federal limits or patient caps impacting the number of patients a practitioner may treat with buprenorphine for OUD, according to a DEA letter.

 Health care providers, including pharmacists, with a DEA registration number that includes Schedule III authority “may not prescribe buprenorphine for opioid use disorder in accordance with their respective state scope of practice.

“In this moment, when the United States is suffering tens of thousands of opioid-related drug opioid poisoning deaths every year, the DEA’s top priority is doing everything in our power to save lives,” said DEA Administrator Anne Milgram. “Medication for opioid use disorder helps those who are fighting to overcome substance use disorder by sustaining recovery and preventing overdoses…. DEA applauds the repeal of the X-Waiver and all it will do to expand access to buprenorphine for those who need it.”

New training requirements were also introduced for prescribers in Section 1263 of the CAA 2023, although these requirements do not go into effect until June 21, 2023.

 Both the DEA and SAMHSA are “actively working on implementation” of this provision.

 Under this section, “the one-time [substance use disorder] education requirement becomes a condition on a controlled medication prescriber’s DEA registration beginning with the first applicable registration,” according to a practice management statement by the American Society of Addiction Medicine (ASAM).

The ASAM statement also noted that health care providers should remain aware of “applicable state laws or regulations that may still be in effect regarding the prescribing and dispensing of buprenorphine” for substance use disorder treatment.

 Additional guidance and clarification should be sought from state officials when necessary.

DEA applauds the repeal of the X-waiver. Drug Enforcement Administration. January 17, 2023. Accessed January 20, 2023. 

https://www.dea.gov/documents/2023/2023-01/2023-01-17/dea-applauds-repeal-x-waiver

Dr Gupta applauds removal of X-waiver in Omnibus, urges healthcare providers to treat addiction. News release. December 30, 2023. Accessed January 20, 2023. 

https://www.whitehouse.gov/ondcp/briefing-room/2022/12/30/dr-gupta-applauds-removal-of-x-waiver-in-omnibus-urges-healthcare-providers-to-treat-addiction/

DEA and SAMHSA eliminate X-Waiver requirements. News release. American Society of Health-System Pharmacists. January 13, 2023. Accessed January 20, 2023. 

https://www.ashp.org/News/2023/01/13/dea-and-samhsa-eliminate-x-waiver-requirements

Policies governing buprenorphine for opioid use disorder. American Society of Addiction Medicine. Accessed January 20, 2023. 

https://www.asam.org/advocacy/practice-resources/buprenorphine-management

Consolidated Appropriations Act, 2023, HR 2617, 117th Cong (2021-2022). Accessed January 20, 2023. 

https://www.congress.gov/bill/117th-congress/house-bill/2617/text

Mann B. 2022 was a deadly (but hopeful) year in America’s opioid crisis. 

Published December 31, 2022. Accessed January 20, 2023. 

https://www.npr.org/2022/12/31/1145797684/2022-was-a-deadly-but-hopeful-year-in-americas-opioid-crisis

Removal of DATA Waiver (X-Waiver) requirement. Substance Abuse and Mental Health Services Administration. Updated January 12, 2023. Accessed January 20, 2023. 

https://www.samhsa.gov/medication-assisted-treatment/removal-data-waiver-requirement

United States Department of Justice. Drug Enforcement Administration. Letter. January 12, 2023. Accessed January 20, 2023. 

https://www.deadiversion.usdoj.gov/pubs/docs/A-23-0020-Dear-Registrant-Letter-Signed.pdf

New legislation removes what many perceived as a barrier to treating opioid use disorder. 

DEA Joins Health Care Organizations in Applauding Repeal of X-Waiver Program

The FDA has accepted for review a New Drug Application (NDA) from Opiant Pharmaceuticals for OPNT003 nasal nalmefene, a product candidate for the treatment of opioid overdose, according to a company press release.1 The NDA has also received a Priority Review designation and a Prescription Drug User Fee Act (PDUFA) date of May 22, 2023.

OPNT003 is a nasal formulation containing high affinity opioid antagonist nalmefene. Results supporting the NDA submission come from 3 studies: a phase 1, open-label, randomized, 2-period, 2-treatment, 2-sequence crossover pharmacokinetic study in 68 healthy volunteers comparing the drug to an intramuscular nalmfene injection (

); a phase 1, open-label, randomized, 3-period, 3-treatment, 6-sequence randomized crossover pharmacokinetic study in 24 healthy volunteers comparing a different 3 different dosing options (

); and a phase 1, open-label, 2-part pharmacodynamic study comparing the drug to naloxone HCl (Narcan) nasal spray 4 mg (

Provisional data from the CDC indicate that in the 12-month period ending August 31, 2022, more than 81,000 people died of an opioid overdose, with 90% of those deaths associated with potent synthetic opioids.

“We are delighted to announce that the FDA has accepted Opiant’s NDA for filing and designated it priority review status,” said Roger Crystal, MD, Opiant president and CEO. “We believe the data supporting this NDA indicates that OPNT003 can potentially offer first responders and communities an important treatment option in tackling the very serious opioid overdose crisis.”

The development of OPNT003 was supported by an award for up to $10.8 million from the Biomedical Advanced Research and Development Authority and a $7.4 million grant from the National Institute on Drug Abuse.

Opiant Pharmaceuticals announces FDA acceptance and Priority Review of NDA for OPNT003, nasal nalmefene, for opioid overdose. News release. Opiant Pharmaceuticals. January 19, 2023. Accessed January 20, 2023. 

https://ir.opiant.com/news-releases/news-release-details/opiant-pharmaceuticals-announces-fda-acceptance-and-priority

The PDUFA date has been set for May 22, 2023. 