On November 17, Tyruko (reference product, Tysabri) became available to treat relapsing forms of multiple sclerosis (MS), in addition to Crohn’s disease. This agent is the first biosimilar to treat MS in the United States.

Manufactured by Polpharma Biologics and commercialized by Sandoz, Tyruko was approved by the FDA in August 2023, but its launch was delayed by FDA’s certification of a test for the JC virus, which must be administered before infusing natalizumab. Sandoz has partnered with Labcorp to administer the JC virus test (which is paid for by Sandoz).

In a press release from Sandoz, Leslie Ritter, Vice President of Healthcare Access for the National MS Society, stated, “For people living with MS, cost and access to care remain significant barriers. The availability of a biosimilar is an important step forward in making medications more affordable.”

Tyruko is available in Europe, and Sandoz has the exclusive license to market the product globally. Biogen reported US net 2024 sales of Tysabri at $920 million, an 8% decrease from the previous year. Biogen’s Tysabri revenues in the rest of the world decreased by 10%, which they attributed to growing biosimilar marketshare.

Natalizumab has about 5% marketshare of the MS category, partly the result of its black box warning for the risk of progressive multifocal leukoencephalopathy, a potentially fatal, brain infection caused by the JC virus. The test for the JC virus seeks the presence of antibodies to the virus. The MS category is dominated by Ocrevus, which has generated more interest in biosimilar development, but will not come off patent until late 2028.

Keren Haruvi, President of Sandoz North America, said, “As the only biosimilar available to treat MS in the US, Tyruko has an important opportunity to help people with MS navigate this disease in a way that is more cost effective. We are proud to be expanding the reach of natalizumab, which underscores our commitment to our purpose of pioneering access for patients.”

No other biosimilar manufacturer has disclosed a biosimilar candidate for natalizumab. Limited competition could restrict cost savings on the agent. A request for Tyfuko pricing information from Sandoz was not answered at the time of publication.

As we reported last month, Tyruko will be the first biosimilar therapy for neurology practices. It will be interesting to see how quickly (or how slowly) they gain comfort in prescribing a natalizumab biosimilar.

On November 17, Organon and its China-based partner Henlius announced that the FDA has approved the first pertuzumab biosimilar. The Perjeta biosimilar was dubbed Poherdy (pertuzumab-dpzb).

Poherdy is approved for use for all of the indications of the reference product Perjeta (manufacturer, Roche). Pertuzumab is an HER2/neu-receptor agonist that is used in combination with trastuzumab and docetaxel for the treatment of HER2-positive metastatic breast cancer in patients who have not received prior anti-HER2 therapy or chemotherapy for metastatic breast cancer. This first pertuzumab biosimilar is also indicated for use in combination with trastuzumab and chemotherapy as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer. Additionally, Poherdy can be used as adjuvant treatment in patients with HER2-positive early-stage breast cancer that has a high risk of recurrence.

Jon Martin, Organon’s US Commercial Lead, Biosimilars and Established Brands, stated in a press release, “Not only is Poherdy the first Perjeta biosimilar approved in the US, but its approval also builds on Organon’s recent momentum of expanding our biosimilars portfolio in women’s health and oncology. Our collaboration with Henlius is critical to our goal of making health care more sustainable for US patients.”

Organon and Henlius signed an agreement in 2022 granting Organon exclusive commercial rights to several Henlius-developed biosimilars in the US. In 2024, Roche announced Perjeta net sales of $1.69 billion, about 3% greater than in prior year.

Formerly designated HLX11, Poherdy leads several pertuzumab biosimilar candidates seeking to launch. Organon did not announce a launch date or pricing for the product; we assume that launch of Poherdy will take place in 2026. The main patent for the reference product expired in 2024, and four other manufacturers have publicly disclosed potential biosimilar candidates in this category.

The level of price discounting for Stelara biosimilars has hit a new low (or high), depending on your point of view. Hikma Pharmaceuticals USA announced on November 6 that it has launched Starjemza, its ustekinumab biosimilar, manufactured by Bio-Thera Solutions. Yesterday, Mark Cuban’s Cost Plus Drug Company announced the availability of Starjemza’s low monthly price of $360 per 90-mg dose, for cash-paying patients. This translates to a 98.8% price cut—the wholesale acquisition cost (WAC) of the reference product Stelara is $29,000 per month.

It is unclear if Hikma will be using Cost Plus as its sole pharmacy distributor and whether there will be a higher cost for patients with insurance coverage. The discount that Mark Cuban is offering is available to patients without insurance coverage. This brings up a relevant point in direct to patient dispensing of specialty drugs like biologics. It is clear that $360 per dose for any drug paid out of pocket is not exactly conducive to long-term adherence by the patient, although this would be paid every 8 weeks for a patient with Crohn’s disease receiving chronic injections. Most specialty pharmaceutical coverage in commercial health plans use a flat copay of $100 to $150 per dispensing or a coinsurance of 10% to 30% up to some maximum ceiling (perhaps $225).

Consider that WAC pricing for most of the ustekinumab biosimilars is an average of $3200 per dose. A 10% co-insurance would result in patient out-of-pocket cost of $320 (or likely lower, depending on the plan’s maximum cost sharing). The Cost Plus pricing for Starjemza roughly brings patients without coverage into the same cost-sharing range as patients with insurance coverage.

It does seem that by bypassing health insurance and PBMs to bring these patients the same out-of-pocket costs that insured patients pay after plans receive rebates and discounts, it is a positive. However, is the appeal of direct-to-patient dispensing greater for drugs like GLP-1s or insulins, where the starting costs are much lower than for monoclonal antibodies such as anti-TNF inhibitors and interleukin antagonists?

From the manufacturer’s standpoint, this net pricing brings this particular ustekinumab biosimilar in line with the adalimumab biosimilars. As we reported earlier this year, there is somewhat limited opportunity for a biosimilar company to earn profits when it has to split that $360 q8wk with its manufacturer (Bio-Thera) and pay any royalties that it might have agreed to when signing a marketing arrangement with the reference manufacturer. We do not know if that is the case for Hikma, but it is consistent with previous agreements).

This news still sets the bar far lower on ustekinumab biosimilar pricing; the lowest previously announced available price was for Accord’s Imuldosa at a 92% WAC discount or $2332.00 per month.

Samsung Bioepis Now Under Samsung Epis Holdings

Samsung Bioepis is the subject of a new corporate structure. On November 3, Samsung Epis Holdings Co., Ltd. announced the establishment as a new investment holding company, following the spin-off of Samsung Bioepis Co., Ltd. from Samsung Biologics.

Kyung-Ah Kim, currently President and CEO of Samsung Bioepis, will also take on the same roles for the holding company. In a press release, Ms. Kim said, “By establishing an independent decision-making structure, we see the potential for further growth and investment. Progress is being made to secure next-generation therapeutic technology on the back of the capabilities accumulated through our biosimilar business. With the spin-off, we expect to have more opportunities to explore next-generation growth drivers.”

Any biosimilar manufacturer will tell you that one of the most daunting and delaying issues in biosimilar development is the abuse of the patent system by reference manufacturers. They delay launch by years, resulting in billions in additional revenues for the reference product, and extra workload for the courts.

At last week’s GRx+Biosims meeting, panelists discussed the current state of the patent system facing biosimilar makers today, and prospects for addressing these hurdles to commercialization.

Robert Cerwinski, JD, Managing Partner, Gemini Law, said that although inter partes review (IPR) is generally an inexpensive route for patent disputes (relative to district court cases), the latest US Patent and Trademark Office notice of rulemaking “will effective remove IPR as an option for generic and biosimilar companies.” Public comments on this rule are due November 17.

Sara Koblitz, JD, Director, Hyman, Phelps & McNamara explained that the US allows patent thickets to develop, to the extent that against the same 30 biosimilars worldwide, the reference manufacturers has asserted some 377 patents in the US vs only 46 in Canada and 24 in the UK. “A patent owner in the US may obtain multiple patents with nonpatentably distinct claims. Double patenting is generally prohibited by patent offices around the world, but not in the US,” she said. The USPTO, however, will permit patent owners to meet an “obviousness-type double patenting” challenge by filing a “terminal disclaimer,” which aligns the expiry date of the multiple patents. “This is supposed to ensure that patents claiming the same invention could not inappropriately extend the life of the original, or ‘parent patent.’ Instead, this results in a cluster of patents, and maximum complexity and launch delays,” said Ms. Koblitz.

She provided a case example where 73 patents were claimed based on 14 distinct inventions, but of which 59 patents were non-patently distinct. In this case, 10 patents were created just for the product composition, 7 patents for the primary indications, 18 patents for secondary indications, 21 patents for the initial formulation, and 4 more for the follow-on indication. In Europe, only 8 patents are granted (2 for the product composition, 2 for primary indications, 1 for the secondary indication, 2 for formulation, and none for the follow-on indication).

Biologic manufacturers tend to add patents with terminal disclaimers just as the biologic marketing exclusivity ends in year 12, stated Ms. Koblitz: “Biosimilar manufactursrs must then contest, settle or design around a wave of new patnets that become enforceable just as statutory exclusivity ends. This effectively shields secondary patents from scrutiny.”  

The Eliminating Thickets to Increase Competition (ETHIC) Act (S.2276/HR3269) would “limit patent assertions for biosimilars and generics only to one patent for each patentably-distinct improvement made on the drug.” It would also invalidate all terminal patents in a group if one is invalidated, providing a mechanism for cutting through the patent thicket.

Through the Courts: The Usual Suspects

Mr. Cerwinski described the typical patent litigation journey today, which usually plays out in district court (“with judges who often have little technological expertise”). He said, “Under certain circumstances, the case can wind up in front of a jury, who have even less technological knowledge.”

The biosimilar-enabling legislation—the BPCIA—created “the patent dance,” where the reference manufacturer must assert whatever patents it intends to defend. “One cannot add later to this list, but it could be 40, 50, or 60 patents. Often, the biosimilar manufacturer seeks leverage to force a settlement, which allows the drug to get to market.”

“Generic and biosimilar companies have huge pressure to reduce the risk of patent litigation, both in terms of time and expense.

Rachel Goode, JD, Senior Vice President, and Head of Legal and Intellectual Property, Fresenius Kabi, described another legislative proposal that addresses patent abuse. The Preserving Access to Affordable Generics and Biosimilars Act (S.1096) would prohibit brand sponsors from compensating generic/biosimilar sponsors to delay market entry of a drug that could be substituted for a reference drug. It prohibits anticompetitive agreements in patent settlements, backed with civil penalties. Ms. Goode said that although these settlements intuitively seem to be anticompetitive, IQVIA data argue that they are procompetitive, by getting contested products to the market faster. According to IQVIA, mean savings was $5 billion to the healthcare system, or a $516 million median savings for each molecule that was the subject of such an agreement.   

At the Association for Accessible Medicines’ GRx+Biosims meeting on Wednesday, we heard hints of a major announcement regarding biosimilar 351(k) application requirements. By the time FDA Commissioner Marty Makary, MD, MPH, left the stage, we knew that a new draft guidance would be announced in an HHS press conference that afternoon.

Indeed, HHS Secretary Robert F. Kennedy Jr; CMS Director Mehmet Oz, MD; and Dr. Makary joined to announce that comparative efficacy studies (CESs) will no longer be required for the vast majority of biosimilar candidates. According to the draft guidance, this decision to nix the mandate for large, phase 3 trials, was based on FDA gaining “significant experience in evaluating data from comparative analytical and clinical studies used to support a demonstration of biosimilarity.” This thinking finally catches up with years of scientific scrutiny and experience.

The Move to Remove the Comparative Efficacy Study Requirement Was not the Administration’s Idea

Biosimilars have been approved for 10 years in the United States and for almost 20 years in the European Union. The idea that these confirmatory studies did not contribute to the totality of evidence of biosimilarity, has been growing since 2019 with advocates like Chris Webster, Hillel Cohen, and Gillian Woollett. Most recently, Sarfaraz Niazi, PhD, has been lobbying Sarah Yim, MD, at the office of biosimilars and biologics to remove the mandate for comparative efficacy studies. We’ve argued in the past that the primary objective of these studies and the study populations used were insufficient to prove any clinically significant difference between a biosimilar candidate and the reference product, based on the work of these scientists.

That the FDA finally was able to pull the trigger on a draft guidance reflecting this reality was both gratifying and frustrating, simply because it has taken so long. At the press conference, the Trump administration took a victory lap for making it happen. In fairness, Health Canada only made this decision on June 10. Dr. Makary claimed that this would reduce the cost of biosimilar development by some $100 million and cut the time to approval by several years. That and future work to streamline biosimilar development could bring the total cost of research and development down below $100 million or considerably less if issues like utilization of a single global reference product were finally resolved.

Critical questions that need to be addressed involve timing. The draft guidance will not become a finalized document for around 6 months. To which biosimilar candidates will it first be applied? For reference drugs expecting biosimilar competition through 2029, CESs have largely begun (at least recruiting), and this includes some of the highly anticipated big-ticket items like Keytruda and Opdivo. When can a prospective biosimilar manufacturer forget about conducting a late-stage CES?

Another Draft Guidance to Come: Interchangeability

Furthermore the press conference promised new draft guidance on the elimination of the interchangeability designation for specific biosimilar products. This also has been many years in the making, though the HHS Secretary, CMS Director, and FDA Commissioner were eager to take credit for finally making it happen. Part of the issue was that interchangeability was written into the BPCIA legislation, and it would seemingly take an act of Congress to remove it. However, acts of Congress seem to be a thing of the past.

Instead, the administration took a different tact, according to Dr. Makary. If the FDA has the authority to designate a biosimilar as interchangeable, it also has the authority to designate all biosimilars as interchangeable with their corresponding reference products. Based on that premise, they decided that legislative action was unnecessary.

Although they have the right idea about removing the designation, they are seemingly confused about its impact. In that press conference, HHS Secretary Kennedy erroneously claimed that removing interchangeability would be a huge step forward in reducing the cost of biosimilars. As any biosimilar manufacturer will tell you, having to litigate endless patents by reference manufacturers is by far the greatest limiting factor in speeding these drugs to marketplace and further lowering the cost of biosimilar development.

Interchangeability has always been a red herring for the FDA; the agency could not seem to create consistent policy on interchangeability for many years, with regard to exclusivity of the designation and how interchangeability is actually assigned. The fact has been that payers have not been able to use interchangeability’s automatic substitution provision for creating rapid biosimilar adoption. Nearly all conversion from reference product use to biosimilars under the pharmacy benefit has been through formulary change and reference product exclusion. Further, automatic substitution plays almost no role in medical benefit covered products, yet FDA designated some buy-and-bill products (e.g., ranibizumab) as interchangeable.

Still interchangeability only referred to substitution between this specific biosimilar and the reference product. It did not allow for automatic substitution between different biosimilars in the same drug category. Nor did it clarify in a timely manner how low-dose and high-dose formulations of the same product would be treated for interchangeability purposes within the adalimumab category. In some cases, it was mystifying how the date of first exclusivity for a product was assigned, further muddying the waters and diluting its potential value.

However, real progress in this area has been a long time in coming. We’ll be happy to see the interchangeability designation placed in the dustbin. It was a confusing and ambiguous attempt at improving the biosimilar environment.

The Kaiser Family Foundation recently released its latest annual report on employer-sponsored health care benefit costs. People seem to be aghast that the premium (employer plus worker contributions) for a family health insurance policy is $26,993. As KFF’s CEO Drew Altman stated, “You can buy a new Toyota Corolla Hybrid every year for less than that.” He’s right. The total cost is outrageous.

Who Knew? Anyone Who Looked at the Trend

However, this is not sudden or out of the blue. This reflects three decades of steady health cost escalation. The summary chart from KFF clearly demonstrates a rock-solid slope of price increases. It was 6% higher in 2025 than 2024, but it has ranged from 1% to 7% since 1999. The biggest recent perturbation is in 2021–2023, reflective of nearly no increase in premiums just after the COVID-19 pandemic and a larger jump in 2023 when all of the pent-up health care demand in 2022 resulted in higher premiums the following year.

This post will not address worker contributions vs. employer contributions, although the rise in the former especially, has multiple effects, including lower salary and less discretionary spending. Instead, we’ll focus on the increase in total costs.

I’ve been covering the health care industry since 1987, and virtually every policymaker at that time believed that health care was too costly. Personally, I didn’t think so, because I had no exposure to it. My employer paid my premium in full, and it was a zero-deductible health plan. Nearly all private health care was obtained through employers. Both public and private employers and the federal government were increasing their use of managed care plans like HMOs and PPOs to combat these rising costs. Yet the increase in costs continued, unabated. A well-known professor at Northwestern University’s Kellogg School of Economics, Edward F.X. Hughes, PhD, pointed out repeatedly that without managed care, the slope of health care cost increases may have been far greater. Today, I wonder.

At the time, we blamed the introduction of new technologies and their increasing utilization for the inexorable rise in costs. For example, every hospital purchased an MRI, CT scanner, and often a PET scanner. To pay for that high capital expenditure, hospitals would raise their price for all services. The managed care plans would try to negotiate lower rates with the hospitals and health systems, but that negotiated rate still was greater than in the last contract. Costs never went down. That catalyzed the silly game of hospitals charging increasing amounts for common procedures like knee replacements, and managed care plans reimbursing them a smaller fraction of those amounts. Patients were often asked to foot the rest of the unreimbursed charge (“balance billing”). In the end though, managed care plans did not halt the annual increase in provider costs, and sure enough, premiums rose to pay for the higher costs.

Are Drugs the Main Reason for Rising Health Costs?

By the late 2000s and mid-2010s, it was clear that specialty drugs utilization was rising fast. The specialty pharmaceuticals were accused of being the latest drivers of rising health care costs. Keep in mind that pharmaceutical costs do play a role in rising health care costs, but they have generally represented less than 12% of the total health care spend. Even today, where specialty pharmaceuticals represent more than half of pharmacy costs, this percentage has remained largely unchanged (mainly because the denominator—total health care costs—is growing as well). Hence, the BPCIA was passed, to help us save money through biosimilar competition. And biosimilars have delivered on that promise, to the tune of about $56 billion since 2015 and accelerating, according to the Association for Accessible Medicines. But total pharmaceutical spending in the US was $450 billion in 2023 alone (an 11% increase from the previous year). This represented only 9.1% of total health care spending in 2023 ($4.9 trillion).

Increased pharmaceutical spending should not be looked upon negatively; it is generally associated with lower acute, emergency, and urgent care spending. Greater use of biosimilars can contribute to greater care value, as greater use of generics contributed in this respect in the 1980s and 1990s. The biosimilars marketed today, later this year, and in 2026, will have a statistically significant effect on curbing pharmaceutical spending, especially in specific drug categories.

In the United States, however, biosimilars are funding two separate, important health care benefits: (1) getting effective biologic medications to greater numbers of patients who may benefit from them and (2) providing the means to shift resources to pay for new and expensive technologies. Biosimilars will not lower overall pharmaceutical spending, until we run out of new treatment technologies to research and use. Both benefits are highly valued and judged by society to be worthwhile. Overall, though, pharmaceutical costs will not level off or decrease any time soon.

The Affordability Tipping Point

Note that it will be less possible each year to shift additional costs to workers, patients, and their families (households now shoulder 27% of total healthcare spending). Indeed, cost shifting and premium sharing are the only reasons that employer-based health insurance still represents the largest segment of the private market.

We are at a tipping point for personal out-of-pocket spending on premiums and care, as we await the outcome of Congressional action on the Affordable Care Act subsidies. Get ready for a sizable boost in the uninsured. Hopefully, they can afford biosimilars and generics, at least. They won’t be able to afford a new Toyota Corolla Hybrid every year. Who can?

More than 2 years since the approval of the natalizumab biosimilar (reference product, Tysabri), partners Sandoz and Polpharma Biologics have yet to introduce neurologists to the concept of biosimilar prescribing. The reason is a JC virus test submitted by the biosimilar manufacturers, which is required for patients prior to receiving natalizumab treatment, has not yet been approved by the FDA. Natalizumab carries a small risk for progressive multifocal leukoencephalopathy (PML), and the presence of JC virus antibodies can help identify those at higher risk for PML, which is potentially fatal.

The launch of Tyruko was to be a prelude to the main event—the first ocrelizumab (Ocrevus) biosimilar; natalizumab is utilized by around 5% of all patients with relapsing forms of multiple sclerosis (MS) who are receiving pharmaceutical treatment. Tysabri is also approved for use in Crohn’s disease, but utilization is negligible relative to the immunomodulators, anti-TNFs, and interleukin monoclonal antibodies.

In 2024, Ocrevus accounted for about half of all MS drug market share, and approximately $6.1 billion in net US sales revenues in 2024 for its manufacturer (Genentech, and its parent Roche). This represented a 5% increase over the previous year’s sales.

It was first approved March 28, 2017, which would allow its market exclusivity period to run through March 2029. The primary US patent is expected to expire sometime after October 2028.

The following are the leading, publicly disclosed ocrelizumab biosimilar candidates.

Amgen’s ABP 692

Amgen is currently recruiting candidates for a phase 3 trial for its infusible ocrelizumab biosimilar candidate ABP 692. This study, in patients with relapsing-remitting MS, is expected to have preliminary results in January 2027. Amgen has a good record of getting their biosimilars to market first, so we wouldn’t count them out here.

Celltrion’s CT-P53

Similarly, Celltrion has begun recruiting study participants for its infusible product CT-P53, with initial results to be available in early 2027. This investigation plans to test an estimated 512 patients.

Polpharma Biologics’ PB018

Polpharma, which is partnered with Sandoz on the commercialization of its natalizumab biosimilar Tyruko, is also working on the competing MS product ocrelizumab. Designated PB018, this product is in preclinical development. Without a commercialization partner at the moment, Polpharma may be willing to move forward if the FDA does follow through on its intention to no longer mandate large phase 3 comparative efficacy studies. We’ll see whether Sandoz or another major player wants to enter the fray with PB018.

Another Contender, and a Fly in the Ocrevus Biosimilar Ointment

An Iranian company, CinnaGen, has phase 3 results for an ocrelizumab biosimilar product it calls Xacrel. This company does not have a history of marketing to the US, and it is unknown whether it intends to find a marketing partner and file its first 351(k) application in the US.

Interestingly, no record of any BPCIA patent proceeding involving Ocrevus is listed on our favorite patent litigation source, Big Molecule Watch. We’ll need to stay tuned for more developments regarding patent litigation, particularly because there is a significant complicating factor with ocrelizumab.

In 2024, Roche received approval for a subcutaneous injection, known as Ocrevus Zunovo, which offers the convenience of a 10-minute injection versus a 4-hour infusion for the older form, both given every 6 months. If interested in producing a subcutaneous form, a biosimilar maker would have to create its own, assuming this formulation gains increasing utilization. I suspect that the reference manufacturer believes it will be able to convert the majority of its patients and new prescriptions to the subcutaneous form by the time a biosimilar is approved and launched. If that is the case, Roche may be less concerned about vigorously defending its patents on the original intravenous formulation in 2028/2029.

All of the clinical studies by Amgen, Celltrion, or Polpharma mentioned above tested the intravenous formulation only of their biosimilar. Celltrion in particular has some experience in this area, with the 2023 approval of its subcutaneous form of infliximab (dubbed  Zymfentra). This approval, subsequent to its initial approval of the biosimilar Inflectra, however, was not considered as a biosimilar but as a follow-on biologic.

In an expansion on their previously announced alliance, Biocon Biologics will begin manufacturing a private-label version of insulin glargine for Civica, which Civica will then commercialize in the US. Biocon will continue to market its own brand of insulin glargine biosimilar (Semglee/insulin glargine-yfgn).

Civica is a nonprofit pharmaceutical company, that was founded to expand access and affordability of low-cost medicines in the United States. It has primarily served as a supplier of generic drugs, with a focus on drugs subject to shortage, to hospitals and health systems. In March, we reported that the two organizations were collaborating on producing an insulin aspart biosimilar (wherein Biocon would supply the raw materials, and Civica would manufacture a biosimilar product, as well as commercialize it).

According to this latest press release, Civica will market the private-label insulin glargine biosimilar under its own branding in all states but California, where it will “carry the CalRx brand.”

“By extending our collaboration with Civica, Inc. to include insulin glargine, we are building on our differentiated approach to serving and enhancing patient access—by retaining our direct commercialization and through this strategic partnership,” said Shreehas Tambe, CEO and Managing Director, Biocon Biologics. “This collaboration enables us to reach underserved populations through new channels in direct alignment with our mission.”

The news report did not specify when Civica will begin marketing the insulin glargine biosimilar from Biocon.

In Other Biosimilar News

Celltrion’s Yuflyma adalimumab biosimilar was approved on October 17 for two additional pediatric indications of the reference product Humira: hidradenitis suppurative in adolescents and uveitis in pediatric patients.

Enoby and Xtrenbo are the latest denosumab biosimilars to receive FDA approval, referencing Prolia and Xgeva, respectively. The approval, announced October 14, is the seventh denosumab biosimilar.

Both are designated denosumab-qbde. Enoby is approved to treat the principal osteoporosis-related indications of Prolia, and Xtrenbo’s approval matches the oncology-related skeletal indications of Xgeva.

Gedeon Richter’s partner Hikma USA will commercialize these biosimilars in the US. ”The approvals of Enoby and Xtrenbo represent a significant milestone accomplishment for Richter, as our first FDA approved biosimilars,” stated Dr. Erik Bogsch, Head of the Biotechnology Business Unit at Richter. “They are a testimony to Richter’s ambition in providing affordable biosimilar access in important therapies to patients across the globe and establishing Richter as a high-quality biosimilar developer and manufacturer.” 

Hikma is already involved in the US biosimilar market, as the commercialization partner of Bio-Thera for the ustekinumab biosimilar Starjemza. This latest news represents the first US biosimilar approval for the manufacturer Gedeon Richter.

The company has a strong presence in the EU and in women’s healthcare. The company’s website lists a tocilizumab biosimilar in clinical development, and two nondisclosed biosimilars in the autoimmune space in early characterization stages. Gedeon Richter also has a 10% equity stake in another biosimilar player—Formycon.

(Editor’s Note: This post was revised to reflect an initial posting error: Hikma is not owned by Gedeon RIchter.)

On October 9, Celltrion, Inc. announced it had received the nod from the FDA on the latest aflibercept biosimilar, Eydenzelt (aflibercept-boav). This Eylea biosimilar is indicated for the treatment of neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy.

Celltrion will join a heavily competitive field when it does launch, as it is the sixth aflibercept biosimilar to receive approval in the US. “Timely access to effective therapies is essential for individuals affected by retinal diseases. We are proud to have Eydenzelt approved by the FDA, and we look forward to expanding the availability and access of biological treatments across the US,” said Dr. Juby Jacob-Nara, Senior Vice President and Chief Medical Officer at Celltrion USA.

Outside of Amgen’s at-risk marketing of Pavblu, which launched a year ago, it is likely that other aflibercept biosimilars won’t launch until at least mid-2026. In an Email to BR&R, a Celltrion spokesperson stated, “At this time, we are engaged in ongoing litigation concerning the US launch of Eydenzelt. As the legal proceedings progress, the final decision regarding the product’s availability will be determined. We are committed to ensuring that all regulatory and legal considerations are thoroughly addressed to facilitate timely access to Eydenzelt for patients in need.” Interestingly, Celltrion also has a bevacizumab biosimilar (Vegzelma). Though not approved by the FDA for ophthalmologic indications, bevacizumab is often used in compounded formulations to provide a very low-cost alternative to ranibizumab and aflibercept and is typically covered by payers. The extent to which one of the several bevacizumab biosimilars versus the reference product Avastin is used to treat retinal disease is unknown.