Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Investigators from the University of Utah said they found no additional safety or clinical risks in a study of patients who were switched from originator infliximab to infliximab biosimilars. The participating institution, University of Utah Health Plans, achieved average savings of $11,508 per patient transitioned to a biosimilar.

The study findings are significant in part because health centers often start only new patients on biosimilars, for fear of destabilizing patients who have achieved disease control with the reference drug. The result is that for patients “grandfathered” to receive the reference product, the potential savings from biosimilars are forgone.

The strength of the study prompted the Academy of Managed Care Pharmacy (AMCP) Foundation to honor lead author 

 with the AMCP Foundation/CVS Health Best 

by a Resident or Fellow at the AMCP Nexus 2020 Virtual meeting on October 21, 2020.

Although multiple studies have demonstrated that switching patients with autoimmune disorders to an infliximab biosimilar is safe and efficacious, most physicians do not support nonmedical switching of patients who have achieved stability with the reference product Remicade because of concerns about effective management, patient mental health, and treatment safety and efficacy, the authors said, citing survey data.

Starting in February 2019, University of Utah Health Plans began switching all patients to biosimilar infliximab who were receiving Remicade originator infliximab. The primary end points were financial and clinical outcomes.

The study enrolled 63 patients (47.6% male, 52.4% female) ages 13 to 63 years. Savings calculations were based on the cost per 100 mg of the most recent Remicade infusion compared with subsequent biosimilar costs for the same patient. Patients included those with commercial (n = 42) and Medicaid coverage (n = 21), or 66.7% and 33.3%, respectively. Disease types included Crohn disease (47.6%), ulcerative colitis (17.5%), rheumatoid arthritis (12.7%), psoriatic arthritis (6.3%), and others.

A number of patients had been previously treated with other biologics, including adalimumab (29.5%) and etanercept (14.8%).

By April 2020, more than 90% of patients who began on the reference infliximab had been switched to a biosimilar. At a mean follow-up of 6.2 months, 44 (70%) of the 63 patients were on infliximab at the same or lower dose. Investigators said 9 patients had unstable or active disease before or after the switch and were given an increase in dosage or frequency of administration.

The savings for the health plan amounted to nearly $725,000, investigators said.

“Transitioning patients from the originator product to a biosimilar did not come with excess safety or clinical risks,” authors said. “The transition process included direct outreach via telephone to providers’ offices and was generally well accepted by all affected physicians.”

They said the findings suggest that the switching model could be applied to other patient populations. They recommended that in future investigations, patients be stratified by disease severity and treatment history to shed further light on the cost and cost and clinical efficacy relationship between reference infliximab and its biosimilars.

Parker T, Britton L, Willis C, et al. A retrospective analysis of the clinical and financial outcomes of converting patients from originator Remicade to an infliximab biosimilar. Presented at:

 AMCP Nexus 2020 Virtual; October 21, 2020. 

Articles

A study of mandatory switching for patients with rheumatologic conditions led to savings without effect on safety or efficacy.

Safety, Efficacy, and Savings Result From Study of Nonmedical Switching

With Amy Coney Barrett’s bid for a seat on the Supreme Court almost a done deal, the question in the biosimilars world is how her potential confirmation is likely to affect the Supreme Court’s pending deliberations on the Affordable Care Act (ACA) and whether the biosimilar approval pathway, which is part of that, survives.

On November 10, the Supreme Court will hear oral argument on whether the individual mandate portion of the ACA is severable from the entire statute or the whole of the ACA should be abolished, which would mean the end of the Biologics Price Competition and Innovation Act (BPCIA), which defines the biologics approval pathway. Legal experts interviewed by The Center for Biosimilars® had mixed opinions on whether Barrett is likely to side with the severable or non-severable arguments.

“Although some of Judge Barrett’s writings have questioned the constitutionality of parts of the ACA, she has not really addressed the severability issue,” said Chad Landmon, intellectual property and FDA chair for Axinn, Veltrop & Harkrider of New York, New York. This makes it difficult to read how she may vote on the issue, he said.

“Given that Justice [Antonin] Scalia was against finding severability, it’s certainly possible that she would come to the same conclusion because, in her own words, Judge Barrett shares Justice Scalia’s judicial philosophy. That being said, it’s also possible that some of the other, newer justices, such as Justice Brett Kavanaugh, would also conclude that the ACA is severable and preserve the BPCIA,” Landmon said.

Ha Kung Wong, an intellectual property attorney with Venable Fitzpatrick of New York, agreed that it’s not clear what Barrett’s opinion on ACA severability would be. In a 2017 

 Barrett discussed the challenge to the individual mandate, but does not appear to have specifically addressed the severability issue or whether she feels the parties to the case have legal standing to challenge the ACA, he noted.

“She’s most likely going to side with the conservatives on the court, but Justice Kavanaugh appears to prefer to sever provisions that are unconstitutional and not strike down whole laws, as he did in 

Barr v American Assn. of Political Consultants

, and Barrett comes from a similar conservative mold as Kavanaugh and Justices John Roberts and Neil Gorsuch. Also, Roberts previously upheld the individual mandate in 2012, based on Congress' taxing power, apparently due in part over concerns regarding the impact of voiding other parts of the ACA,” Wong said.

 originally required that individuals must maintain a certain amount of health insurance or pay a penalty for failure to do so, but the penalty portion was eliminated in January 2019, and plaintiffs may be found to have no standing to contest the ACA because they have failed to produce evidence of financial harm from the individual mandate. The court may uphold the lower court finding that the individual mandate is unconstitutional but decide that other parts of the law are valid and may stand independently, in accord with what may be perceived as the original intent of Congress when it voted on the legislation.

“We’ve seen that the ACA can operate without the individual mandate penalty, as it has done over the past year, so it doesn’t appear to be necessary for the ACA as a whole,” Wong said.

In the event of a nonseverable decision, the loss of the BPCIA could be devastating for the progress made with biosimilars, lower-cost copies of reference products that have benefited from this pathway to approval, which also adds structure to the process of resolving patent disputes, legal experts said.

“The smart thing to do would be a severability determination,” said Kevin Nelson, a partner with Schiff Hardin, of Chicago, whose practice has focused on biologics regulations. “Some of the amicus briefs have talked about that opportunity and emphasized how the BPCIA is a really a standalone provision and is not intertwined with the ACA. The responsible thing would be to segregate the BPCIA regardless of what you do with the ACA.”

The court seems primed to do this based on the philosophy that has encompassed its previous actions, he said. “There is a tradition on the Supreme Court of not striking down more of a statute than it needs to. The Supreme Court is not Congress. It has acknowledged that time and again. It’s not about rewriting laws. It’s about determining what’s constitutional and what’s not,” Nelson said.

If the Supreme Court were to rule on the side of nonseverability, it might be a very long time before Congress is able to enact a replacement for the BPCIA, he added. “We’d be asking Congress to do something that it’s having trouble doing right now, and that’s agreeing to stuff.” The election and the changes in representation it brings about would complicate the issue.

A trio of legal experts discuss Amy Coney Barrett's bid for a Supreme Court seat and how that might affect deliberations on the Affordable Care Act and the Biologics Price Competition and Innovation Act (BPCIA).

Legal Experts Weigh in on BPCIA Severability

Samsung Bioepis presented positive data from real-world switching and uptake studies of infliximab biosimilars in patients with inflammatory bowel disease (IBD) at the American College of Gastroenterology (ACG) 2020 Annual Scientific Meeting.

an 83% continuation rate among patients who were switched from reference infliximab (Remicade) to the biosimilar Renflexis. Investigators culled patient population data for the retrospective study from the US Veterans Affairs Healthcare System database.

The same study showed a similar continuation rate among patients who were switched from 

another biosimilar, to Renflexis, “reflecting the safety of switching from either reference product or biosimilar,” Samsung Bioepis said in a statement.

“Since IBD symptoms can be severe, maintaining a stable condition is important for IBD management. This study demonstrated that patients who were on infliximab, reference product or biosimilar, can remain stable after switching to another biosimilar, without major safety concerns,” said study leader Nabeel Khan, MD, an associate professor of clinical medicine at the University of Pennsylvania. 

that adoption of Renflexis, which became the preferred infliximab product on the Veterans Affairs National Formulary (VANF) in 2018, was faster than adoption of Inflectra. The latter became listed on the VANF in 2017, suggesting that providers are becoming more comfortable with the use of infliximab biosimilar agents.

“We are confident that this real-world switch data will provide additional reassurance to gastroenterologists who are treating patients with IBD,” said Seongwon Han, vice president and Medical & Lifecycle Safety team leader at Samsung Bioepis.

Renflexis was approved by the FDA in 2017. The goal of the first study was to augment data on the safety of switching in the real world. Patient data from January 2017 to May 2020 were included, and study requirements were that patients must have begun Renflexis prior to May 1, 2019, to provide sufficient follow-up. A minimum of 2 infusions of reference infliximab or Inflectra were required prior to initiating treatment with Renflexis, and patients must have switched to Renflexis after 3 months of stable IBD. The primary end point was Renflexis discontinuation at the 1-year point.

The investigators included 298 patients in the study and observed a 1-year Renflexis discontinuation rate of 17% (n = 52). They said 30 (10%) patients discontinued following cessation of response, which included development of resistant antibodies. Hypersensitivity led to discontinuation for 9 patients (3%).

The continuation rates for patients with a double medication switch (reference to Inflectra to Renflexis) and those with a standard single medication switch (reference to Renflexis) were similar: 82% and 87%, respectively.

The investigators noted that 13% of patients discontinued after loss of response or hypersensitivity reactions, leading them to conclude that switching from reference/Inflectra to Renflexis “through a single or double switch is relatively safe in a nationwide cohort of stable IBD patients.”

Rising Comfort Level for Infliximab Biosimilars

The second study described infliximab reference product use as the VANF policy transitioned to use of biosimilars. Again, the study looked at use of Remicade, Inflectra, and Renflexis. The originator drug was the preferred infliximab until May 2017, before it was replaced by Inflectra in that position from May 2017 to September 2018. Renflexis has held the preferred position since September 2018.

Patients with a treatment history may continue the nonformulary product under the VANF policy, but new patients must use the preferred product. These investigators studied 6 months of infliximab utilization data and found that infliximab products were used to treat 3488 veterans with IBD (60.2%, Crohn disease [CD]; 39.8%, ulcerative colitis [UC]) and the mean age was 52.5 years. Ninety percent of the patients were male.

The investigators said the mean time for the preferred formulary product to become the most commonly used product among veterans was 10 months for Inflectra and 2 months for Renflexis.

They said the percentage of patients treated with an infliximab biosimilar increased more than 800-fold (0.1% to > 86%) from the beginning to the end of the study. Prescribing patterns were similar in both UC and CD. The investigators noted no significant difference in utilization patterns for the various infliximab products, “suggesting that [Inflectra] and [Renflexis] are used in the same manner as [infliximab] originator.

They concluded that the rapid increase in use of these agents during the study period suggests that providers are becoming more comfortable with the use of biosimilar infliximab products in the treatment of IBD.

1. Pernes T, Patel M, Khan N. The safety of switching from originator infliximab or biosimilar CT-P13 to SB2 among a nationwide cohort of inflammatory bowel disease patients. Presented at: ACG 2020 Annual Scientific Meeting; October 23-28, 2020. P1597.

2. Johnson J, Sauer BC, Pinnell DK, et al. Infliximab biosimilar use for inflammatory bowel disease: a National Veterans Affairs experience. Presented at: ACG 2020 Annual Scientific Meeting; October 23-28, 2020. P1570. 

A retrospective analysis of data from the US Veterans Affairs Healthcare System database provides positive switching data for infliximab products.

Samsung Bioepis Presents Real-World Switching Data for Renflexis

Biocon, which launched an insulin glargine product on the US market in August, reported increased revenue of $238 million for the quarter just ended, driven by 11% growth in biosimilar sales, as well as growth in research services (12%) and generics revenue (8%). The net profit was $23.6 million.

Revenue for the company’s biosimilar products totaled $91.5 million, up from $82.2 million. Biocon has commercialized biosimilar versions of trastuzumab, pegfilgrastim, bevacizumab, and adalimumab in markets around the world. Besides insulin glargine, it also produces rh-insulin.

During the quarter ended September 30, Biocon 

the long-acting insulin glargine product Semglee in partnership with Mylan. Because it was approved by the FDA under the Food Drug and Cosmetic Act and not via the biosimilar pathway established under the Biologics Price Competition and Innovation Act, the agent is not officially considered a biosimilar, although Biocon and Mylan have announced intentions of seeking biosimilar and interchangeable status for the product on the US market. 

Interchangeable status would allow pharmacists to dispense the product as a substitute for the reference product Lantus without the need to obtain clearance from the prescribing physician.

“Our insulin glargine, Semglee, was commercialized in the United States by our partner Mylan during the quarter, thus heralding our entry into the US insulins market,” Biocon Executive Chair Kiran Mazumdar-Shaw said in the earnings 

. “With this launch, we have expanded our portfolio of biosimilars and occupy a position of impactful influence in the biosimilars segment.”

Semglee was launched in Spain over the past quarter. In addition, Mylan and Biocon launched an etanercept biosimilar in Europe, and Biocon aims to establish commercial offices in Brazil, Malaysia, United Arab Emirates, and Saudi Arabia.

Biocon said the quarterly growth in biosimilars revenue was led by its trastuzumab biosimilar (Ogivri), which the company said has a 6% share of the US market for trastuzumab (4% and 10% in the 150- and 420-mg product segments, respectively) and pegfilgrastim (Fulphila), which has a 15% share of the prefilled syringe market in the United States.

“Ogivri continues to be the leading biosimilar trastuzumab in Australia and Canada, and it has a double-digit share in 3 markets in Europe,” Biocon said. “For Semglee…we are witnessing encouraging market penetration in certain markets, such as Slovakia and Croatia.”

Biocon had a busy quarter, which included the launch of a long-acting insulin glargine product (Semglee) in partnership with Mylan.


Biocon Reports Biosimilars Revenue Growth

Cambridge, Massachusetts–based Biogen reported biosimilar 

up 13% for the third quarter of 2020, to $208 million. Biogen markets etanercept (Benepali), adalimumab (Imraldi), and infliximab (Flixabi) biosimilars. Benepali revenues were up 7%, or $124 million vs 116 million in the year-ago third quarter; Imraldi, up 14%, or $56 million vs $49 million; and Flixabi, up 49%, or $27 million vs $18 million. 

Etanercept, adalimumab, and infliximab are used in the treatment of autoimmune diseases such as Crohn disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, and psoriatic arthritis.

In total, the company reported third-quarter revenues of $3.4 billion, down 6%.

In October, Biogen and Samsung Bioepis reported that the European Medicines Agency had accepted their 

for approval of a proposed ranibizumab biosimilar (SB11), referencing Lucentis. Ranibizumab is an anti–vascular endothelial growth factor agent indicated for the control of blood vessel proliferation in retinal vascular disease.

Samsung Biologics, a major owner of the biosimilars company Samsung Bioepis, reported a third quarter 2020 operating 

of $50 million on revenues of $241.8 million. The company said sales were up 49% over the comparable 2019 quarter despite a global slowdown caused by the coronavirus disease 2019 pandemic.

In August, Samsung Bioepis’ bevacizuamb biosimilar (Aybintio) was granted marketing approval by the European Commission. The drug was indicated for the treatment of metastatic colorectal cancer; breast cancer; non

small cell lung cancer; renal cell carcinoma; epithelial ovarian, fallopian tube, and primary peritoneal cancer; and cervical cancer. 

During the third quarter, the Incheon, Republic of Korea–based Samsung Biologics announced plans to construct what it called the world’s largest biologics 

, spanning 23.8 million feet. Manufacturing activities are scheduled to begin in the second half of 2022. The company's current 3 manufacturing plants are approaching capacity and in combined floor space do not equal the anticipated size of the new plant.

Earnings fell overall for Biogen, although biosimilar revenues continued an upward climb. 

Biogen, Samsung Report Third-Quarter Biosimilar Results

Shanghai Henlius Biotech will share development and distribution of its bevacizumab biosimilar candidate HLX04 with Zhuhai Essex and Essex Bio-Investment, the company said in a 

The bevacizumab product will be codeveloped for the treatment of ophthalmic diseases such as wet age-related macular degeneration (wAMD). Henlius will handle preclinical and clinical development of the agent, and the Essex companies will collectively be responsible for regulatory filings and commercialization of the drug on global markets.

Henlius will receive up-front and regulatory and commercial milestone payments of $43 million and cumulative payments of $30 million for every $1 billion in net sales above the first $600 million.

The agreement, which also covers sublicensing fees, will help distribute the costs and risks associated with developing and marketing the biosimilar, while making use of the Essex companies’ marketing strengths.

Henlius said the market for this ophthalmic agent appears strong in China, as the incidence of wAMD is increasing year by year, especially among middle-aged and older individuals. The number of affected persons in China is about 5 million, and the globally affected population is close to 30 million, Henlius said.

HLX04 works by blocking the proliferation of blood vessels thought to contribute to macular degeneration, a process known as angiogenesis.

“Via specific binding with vascular endothelial growth factor (VEGF), HLX04 can block the interaction between VEGF and its receptors, thus inhibiting angiogenesis,” Henlius said. “Results from preclinical and clinical studies have demonstrated significant efficacy of VEGF inhibitors on ophthalmic diseases caused by fundus angiogenesis. Since bevacizumab has not been approved for the treatment of ophthalmic diseases globally despite of its broad use, HLX04 has the potential to be one of the first bevacizumabs approved for these indications.”

Hoping to secure indications in China for wAMD and diabetic retinopathy, Henlius has submitted an approval application to Chinese regulatory authorities. This was in January 2019. Global trials are planned to support similar regulatory submissions in Australia, the European Union, and the United States, Henlius said.

Shanghai Henlius Biotech will share development and distribution of its bevacizumab biosimilar candidate HLX04 with Zhuhai Essex and Essex Bio-Investment.

Henlius Inks Global Bevacizumab Biosimilar Distribution Deal

NeuClone’s ustekinumab biosimilar candidate has met 

 for similarity to the reference product (Stelara) in a phase 1 clinical trial, according to a company statement.

The reference version of ustekinumab is indicated for treatment of patients with plaque psoriasis, psoriatic arthritis, Crohn disease, and ulcerative colitis.

The Sydney, Australia-based biosimilar company said its ustekinumab candidate (NeuLara) demonstrated clinical pharmacokinetic similarity to US- and EU-sourced Stelara samples. Safety, immunogenicity, and tolerability profiles of NeuLara also matched the reference product, NeuClone said.

“With successful completion of the phase 1 trial for NeuLara, our ustekinumab biosimilar is now significantly de-risked along its development path to market,” said Noelle Sunstrom, CEO of NeuClone. 

“We are on track for a global phase III trial starting in 2021 and to be among the first biosimilar entrants, making this valuable antibody drug available to many more patients with psoriasis and inflammatory bowel diseases,” she said.

There are no ustekinumab biosimilars currently approved or marketed in either the United States or Europe.

Ustekinumab works by interfering with the cytokine signaling process that influences levels of inflammation in the body. In this way, ustekinumab suppresses the immune response and alleviates inflammatory disease.  

 currently and the agent is among the top 10 drugs by sales, with projected 2024 revenues of 

For a recent interview with NeuClone's strategic analyst Thomas Wakim about the company's foray into biosimilars for PD-1 inhibitors, 

Demonstrated biosimilarity across clinical parameters puts this drug among NeuClone's leading product candidates.

NeuClone's Ustekinimab Candidate Shines in Phase 1 Trial

Step therapy policies, which require patents to fail on a preferred therapy before switching to an agent doctors may consider more appropriate, could end up costing payers more money and shouldering patients with high, up-front out-of-pocket (OOP) costs, according to an Avalere Health 

of patients receiving treatment for Crohn disease, paid for by Bristol Myers Squibb. Avalere is a health care consulting firm.

Avalere said that under a hypothetical step therapy scenario, a patient with Crohn disease and a negative outcome would max out payer deductible and copay requirements as soon as 5 months into a plan year, whereas a patient with no step therapy requirement would not hit the maximum OOP (MOOP) until the end of the 12 month period.

“A patient hitting a plan’s MOOP may be viewed as a positive event due to the capping of any additional costs. However, when the MOOP is hit early in the plan year, patients are responsible for high OOP costs clustered within the first few months of the year as opposed to having costs spread throughout the year,” Avalere wrote.

The resulting clustered payment load can create affordability challenges for patients that may affect adherence to therapy and the pace of disease progression, Avalere said.

In each scenario, the hypothetical patients incurred $4065 in total OOP costs, but in the case of the patient not on step therapy, monthly costs averaged $339. In the non–step therapy scenario, steady disease management using the doctor’s first choice of therapies is assumed. In the step therapy example, the patient switches to the doctor’s choice of therapy in July of the plan year after a negative outcome, Avalere said.

The Avalere analysis indicated that payer costs were 37% higher in the case of the patient on step therapy with a negative outcome: $186,000 vs $136,000.

Often controversial, step therapy policies are also referred to as “fail-first” policies. The Association for Accessible Medicines, which represents many large biosimilar and generic drug manufacturers and developers, has called upon the FDA to establish 

that patients who are stable on biologic reference medicines are candidates for transition to corresponding biosimilars. Payer policies may require patients to fail on a reference product before switching to a biosimilar, which the AAM contends is illogical because biosimilars are identical in efficacy and safety to reference products, so a switch after failure is not likely to produce a positive outcome.

The Avalere analysis mentions the Safe Step Act, which would require group health plans to provide an exceptions process to step therapy requirements. “Stakeholders should continue to monitor the experience patients have with step therapy policies to better understand the effect on patients, insurers, and market dynamics,” Avalere said. The analysis also states that more than half of states have moved to enact step therapy protections for patients.

“Step therapy requires patients to try a preferred drug before gaining access to the drug prescribed by their provider. In some instances, step therapy may provide patients with an effective generic or low-cost treatment option and can therefore be associated with lower patient OOP and insurer costs. In other instances, step therapy may require patients to try a preferred brand option due to considerations related to contracts and rebate negotiations. In those instances, step therapy could serve as an obstacle to getting the product that a provider has deemed most appropriate for their patient and may be associated with delayed treatment, poor patient adherence, or a negative clinical outcome that may cause increased overall costs,” Avalere wrote.

An Avalere analysis suggests costs are more moderate and lower under a no–step therapy scenario for patients with Crohn disease. 

Avalere: Step Therapy May Exacerbate Patient, Payer Costs

Biosimilar competition for Roche added up to a $3.83 billion reduction in sales in the first 9 months of 2020, contributing to a sales decline of 4% in the United States for the pharmaceutical giant.

Roche had a 1% overall decrease in pharmaceutical sales, stating that the coronavirus disease 2019 (COVID-19) pandemic also had a significant effect on revenues for the 9-month period.

Roche markets the originator products Avastin (bevacizumab), Rituxan (rituximab), and Herceptin (trastuzumab), each of which faces international biosimilar competition. In the United States, Roche saw increased sales of Ocrevus (ocrelizumab), Hemlibra (emicizumab), Tecentriq (atezolizumab), Actemra/RoActemra (tocilizumab), and Kadcycla (ado-trastuzumab emtansine); however, the US revenues from these products were offset by biosimilar competition, the company noted.

US pharmaceutical sales dropped to $20.1 billion from $21.9 billion for the first 9 months of 2020, an 8% decrease. Japan sales dropped to $3.0 billion from $3.4 billion, a 9% drop. In Europe, sales dropped $6.85 billion vs $6.90 billion, a 1% decrease.

In Europe, Roche’s sales of trastuzumab, bevacizumab, and rituximab declined 32%, 16%, and 32%, respectively. The company largely attributed the drop to biosimilars.

Sales also decreased 6% in Japan “as a result of the considerable competition from biosimilars, generics, COVID-19, and government price cuts,” the company said.

Overall sales erosion from biosimilars was 22% for Avastin, 27% for Rituximab, and 31% for Herceptin. Roche reported strong worldwide sales gains for new products expected to compensate for biosimilar competition, such as Tecentriq, up 64%; Ocrevus, up 29%; Hemlibra, up 79%; and Actemra/RoActemra, up 33%.

Roche attributes a $3.83 billion reduction in sales to biosimilar competition.

Roche Earnings Hit by Biosimilar Competition, COVID-19

 with a joint plan to obtain FDA approval for a biosimilar onabotulinumtoxinA referencing Botox (AbbVie), Revance announced positive phase 3 clinical trial 

for its daxibotulinumtoxinA (Daxi) injectable, which also would compete with Botox by offering patients longer duration of drug activity and, consequently, fewer trips to the physician for injections.

Revance, of Newark, California, reported positive efficacy, safety, and tolerability findings for the daxibotulinumtoxinA injectable from the ASPEN-1 trial, supporting the concept of reduced physician visits and drug efficacy longevity with this agent.

DaxibotulinumtoxinA is intended for the treatment of cervical dystonia, a chronic neurological condition that causes abnormal movements and awkward posture of the head and neck. Frontline treatment is usually a neuromodulator, such as onabotulinumtoxinA.

Revance said daxibotulinumtoxinA was found to be safe and tolerable in a population of 301 patients randomized to single treatments of 125 or 250 units of daxibotulinumtoxinA or placebo. The study duration was 36 weeks. 

In addition, Revance said patients treated at either dose level achieved a clinically meaningful improvement in cervical dystonia by the fourth and sixth weeks. As measured on the Toronto Western Spasmodic Torticollis Rating Scale, statistically significant improvements were noted in patients who received either the 125- or 250-unit doses (12.7 and 10.9, respectively, vs 4.3 [placebo]; 

The median durations of response were 24.0 and 20.3 weeks for the 125- and 250-unit doses, respectively.

“Currently, most patients with cervical dystonia visit their physician 3 to 4 times a year for injections, which places a heavy burden on patients’ time and schedule,” said trial investigator Joseph Jankovic, MD, a professor of neurology and founder and director of The Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine in Houston, Texas.

“Often, the treatment effect wears off between injections, significantly impacting the quality of their work and personal lives. If a treatment could offer longer duration of effect, thus requiring fewer trips each year for reinjection, I imagine patients would find this quite beneficial,” Jankovic said.

The ASPEN-1 findings improve Revance’s shot at the $5.1 billion global neuromodulator market, said Mark Foley, president and CEO at Revance.

“We are very pleased to report these positive results from the ASPEN-1 phase 3 trial, as this is the company’s second successful phase 3 program demonstrating daxibotulinumtoxinA for injection’s extended duration profile, now across 2 different treatment categories: aesthetics and therapeutics,” Foley said. “In addition to laying the foundation for our therapeutics franchise, these results reinforce its potential in other muscle movement and pain disorders.”

In February 2020, Revance said the FDA had accepted its biologics license application for daxibotulinumtoxinA for the treatment of moderate to severe glabellar (frown) lines. The drug received an FDA orphan drug designation in 2017 for the treatment of cervical dystonia. Orphan drug status confers tax reductions and other advantages designed to spur development of innovative products.

DaxibotulinumtoxinA met all end points in a study demonstrating longer duration of action, safety, and tolerability.