Even at 10% Discount, Eylea Biosimilar Pavblu Offers Lower-Cost Option

Although the FDA has approved five biosimilars of Regeneron Pharmaceuticals, Inc.’s best-selling Eylea (aflibercept), patent infringement lawsuits by the drugmaker have kept those competitors off the U.S. market — until now. Following a successful defense of its Pavblu (aflibercept-ayyh), Amgen Inc. recently launched the drug at risk. The agent is entering an increasingly crowded therapeutic class, but it’s one that’s also costly for payers, which may be seeking some savings, say industry experts. But is its price good enough to pull market share?

Pavblu has approval for all of Eylea’s indications — neovascular (wet) age-related macular degeneration (AMD), macular edema following retinal vein occlusion (RVO), diabetic macular edema (DME) and diabetic retinopathy (DR) — except for retinopathy of prematurity. Among the vascular endothelial growth factor (VEGF) inhibitors approved for ocular use, Eylea is the only one with that indication on its label.

Approved Aug. 23, Pavblu is the most recent of the five Eylea biosimilars that the FDA has green-lighted, and all of the approvals have come in 2024. The others include:

• Sandoz Inc.’s Enzeevu (aflibercept-abzv), which was approved Aug. 9 for wet AMD;
• Formycon AG and Klinge Biopharma GmbH’s Ahzantive (aflibercept-mrbb), approved June 28 for wet AMD, RVO, DME and DR;
• Mylan and Biocon Ltd. subsidiary Biocon Biologics Ltd.’s Yesafili (aflibercept-jbvf), approved May 20 for wet AMD, RVO, DME and DR; and
• Samsung Bioepis Co., Ltd. and Biogen Inc.’s Opuviz (aflibercept-yszy), also approved May 20 for wet AMD, RVO, DME and DR.

Yesafili and Opuviz have interchangeable status with Eylea, and Enzeevu has provisional interchangeability.

Regeneron has filed eight lawsuits claiming patent infringement, with both FDA-approved and pipeline biosimilars of Eylea as its targets. Most recently, it filed a lawsuit (Case No. 3:34-cv-08760) against Sandoz shortly after Enzeevu’s approval. Preliminary injunctions against two of the approved biosimilars are preventing them from launching, while a permanent injunction is holding back Yesafili.

In Amgen’s case (No. 1:24-MD-3103-TSK/1:23-CV-39), a preliminary injunction hearing was held Aug. 13 to determine whether the company can launch Pavblu at risk. The district court denied Regeneron’s motion for the preliminary injunction on Sept. 23, citing two reasons. The first was a difference in formulation: “Eylea contains a sodium phosphate buffer,” noted Chief Judge Thomas S. Kleeh of the Northern District of West Virginia in his ruling, but Pavblu “does not contain a separate buffer component.” In addition, he found Regeneron’s arguments conflicted with ones it made in the earlier case (No. 1:22-cv-00061) resulting in a permanent injunction against the launch of Mylan and Biocon’s Yesafili.

Kleeh then issued a temporary injunction to halt the biosimilar’s launch on Sept 25. After reviewing briefs from both companies, the court then lifted the temporary injunction on Oct. 22, clearing the way for the at-risk launch. The court, however, granted Regeneron’s motion to expedite its appeal, with briefings due this month and oral arguments in January.

The day of the court’s decision, Amgen told Reuters that it would launch Pavblu “as quickly as possible to help expand access to affordable and effective treatment." During the company’s Oct. 30 call to discuss third-quarter earnings, Murdo Gordon, executive vice president of global commercial operations, revealed that Amgen had “fully deployed our team in support of the recent U.S. launch of Pavblu.…Our teams moved quickly to engage retina specialists, and we’re encouraged by the enthusiastic feedback from customers.”

He also said that the company was preparing for two other biosimilar launches: Wezlana (ustekinumab-auub), a biosimilar of Stelara (ustekinumab) from Johnson & Johnson Innovative Medicine, in the first quarter of 2025 and Bkemv (eculizumab-aeeb), with reference drug Soliris (eculizumab) from Alexion, AstraZeneca Rare Disease, in the second quarter. Both agents have interchangeable status.

Experts: At-Risk Launch Was Surprise

It is surprising that Amgen launched Pavblu at risk, says Renee Rayburg, R.Ph., vice president of specialty clinical consulting at Pharmaceutical Strategies Group (PSG), an EPIC company. “They are at financial risk for damages if the courts find in favor of Regeneron for patent infringement, particularly since Regeneron’s appeal arguments are set to be heard in January. At the same time, this is a very lucrative market financially, of which Eylea is the market share leader (2023 reported sales of Eylea in the U.S. were $5.9 billion), so being first to the market with a biosimilar could have some advantages for Amgen.”

“It was anticipated that Amgen would likely delay their launch until the Appeal Court arguments were heard given the risk of potential damages if the courts ruled in Regeneron’s favor,” comments Andy Szczotka, Pharm.D., chief pharmacy officer at AscellaHealth. “It is possible that Amgen is hoping that the ‘at risk’ launch of Pavblu could expedite a legal settlement with Regeneron over the patent issues. However, with reported 2023 Eylea sales of almost $5.9 billion, the potential to gain a portion of Eylea sales likely weighed heavily in Amgen’s decision.”

Those sales, says Rayburg, “accounted for an estimated 35% of market share in this category in 2023, most likely a result of proven efficacy, indications for treatment of multiple eye disorders and opportunity for an extended dosing interval.”

She acknowledges the possibility of a negotiated settlement between the companies but says that “there has been no indication of such discussions in the market so far.”

“It is hard to tell,” says Rayburg, whether Regeneron’s appeal will be successful, “especially since earlier this year the same court ruled in favor of Regeneron to delay the entrance of” Opuviz and Yesafili onto the U.S. market until 2027. But “it is uncertain” whether the buffer distinction “will affect the appeals hearing.”

One wrinkle that could help usher the biosimilars onto the market sooner rather than later is a provision of the Inflation Reduction Act’s (IRA) Medicare drug price negotiation process, notes Szczotka. CMS will establish a Maximum Fair Price (MFP) for high-cost, single-source Medicare drugs. “It is likely” that when the negotiation process expands from solely Medicare Part D to include Part B drugs as well, that due to its expenditures, Eylea will be selected for negotiation in 2026, with prices going into effect in 2028.

“If Regeneron were to reach an agreement that would allow biosimilars to launch prior to the conclusion of the negotiation period (i.e., Nov. 1, 2026), that would allow CMS to identify bona fide aflibercept competition, and this could assist in preventing Regeneron from having to negotiate a price with CMS for Eylea or Eylea HD. This would provide Regeneron the time to continue to switch patients to Eylea HD and avoid the IRA price concessions. This may provide an opportunity for one or more of the biosimilar aflibercept products to reach settlement agreements and be able to launch their FDA-approved product.”

List Price Is 10% Discount to Reference Drug

Also perhaps a surprise is that Pavblu launched with a list price of $1,664 per shot, which is only 10% less than that of Eylea. That price means that “it is not the lowest cost VEGF inhibitor and only provides another therapeutic option for minimal cost savings for patients, payers and providers,” maintains Szczotka. Newer agents within the class have less frequent dosing, “which is generally preferred by ophthalmologists and patients,” he points out. “The 10% discount is unlikely to cause any significant market erosion for Eylea, especially since lower-cost options are currently market available.”

“It is not too likely that price point can move much market share unless there are other incentives available, such as better contract prices, rebates, copay assistance or other patient or provider incentives which have not been disclosed as of yet,” adds Rayburg.

Pavblu is entering a fairly competitive therapeutic class. It includes not only Eylea but also a higher dose formulation of that agent known as Eylea HD; Novartis Pharmaceuticals Corp.’s Beovu (brolucizumab-dbll); Roche Group unit Genentech USA, Inc.’s Lucentis (ranibizumab), Vabysmo (faricimab-svoa), Susvimo — a version of ranibizumab for intravitreal use via an ocular implant — and cancer drug Avastin (bevacizumab), a compounded version of which is used off-label in ocular indications but is currently experiencing a shortage; and two Lucentis biosimilars: Samsung Bioepis and Biogen’s Byooviz (ranibizumab-nuna) and Sandoz’s Cimerli (ranibizumab-eqrn).

“In our 2023 Artemetrx book of business for eye disorders, Eylea holds a market share of 70.4% based on spend,” says Rayburg. “It is followed by Vabysmo at 15%, Lucentis at 8.3%, Cimerli at 4.5% and Avastin at 1.1%. When examining market share by claims, Eylea has a share of 56.2%, followed by Avastin at 16.5%, Vabysmo at 11.6%, Lucentis at 11% and Cimerli at 3.4%.”

But while Eylea currently is No. 1 in the class, others are pulling market share. According to Prime Therapeutics LLC’s recently released Medical Pharmacy Trend Report, Eylea ranked No. 2 in Medicare per-member per-month (PMPM) spend, but that spend actually decreased by 0.9% due to increased use of Vabysmo.

Prescribers Take ‘Very Particular’ Approach

Payers may have utilization management for the class that requires using a lower-cost option first, including off-label Avastin and the Lucentis biosimilars, says Rayburg. “What makes these eye disorders unique is that patients visit the physician's office for their injections. During these visits, physicians can evaluate their patients' visual acuity to determine how well the drug, dosage and dosing frequency are working for them. As a result, prescribers can be very particular over which drugs they are prescribing, as they have the ability to actively assess the benefits of drug therapy each time the patient comes in.”

Because the agents are intravitreal injections administered by a provider, they are primarily covered under the medical benefit and acquired via buy and bill, with payers reimbursing ophthalmologists for the drug and their administration of it. However, Szczotka says that “there is a growing trend to have the VEGF inhibitor provided by a payer’s contracted specialty pharmacy (i.e., white bagging) directly to the provider office in those cases where the provider office does not wish to purchase the product or by the payer’s preference. In this situation the product cost would be covered under the pharmacy benefit, while the professional administrative fees would be part of the medical benefit.”

Which benefit the drugs fall under also impacts interchangeability for the biosimilars, two of which currently have that designation. That status, says Szczotka, “may not be a significant advantage for these products since the primary benefit coverage for Eylea is typically under the medical benefit. Interchangeability generally applies to when drug products are dispensed by pharmacies, not under a buy-and-bill arrangement. This may only be applicable to those situations where white bagging is in use for aflibercept.”

Ultimately, says Rayburg, “a Pavblu launch offers an opportunity for a lower-cost option to this market-share leading brand drug that’s likely a top driver of spend in this therapeutic category for most payers. Additionally, this therapeutic category is expected to grow as we continue to face an aging population in the U.S.”

This infographic was reprinted from AIS Health’s monthly publication Radar on Specialty Pharmacy.