FDA Approves Semglee Insulin Glargine as First Interchangeable Biosimilar

The FDA has approved Biocon Biologic's Semglee insulin glargine as an interchangeable biosimilar, referencing Lantus. The approval carries with it many hopes for stronger competition in the insulin market, which is dominated by a handful of brands and characterized by stubbornly high prices.

The approval of Semglee was much anticipated; it is also the first biosimilar decision for the year, during which the FDA has been preoccupied with addressing the need for COVID-19 treatments and vaccines. The product launched last year without the interchangeability designation.

An interchangeable designation means that Semglee can be substituted for Lantus automatically by pharmacists without physicians' permission. All states have enacted laws in anticipation of interchangeable biosimilars, however, and these describe conditions under which pharmacists can substitute these agents. Predominantly, patients must be told they're getting a biosimilar substitute for the reference product and some type of registry must be created so physicians can find out that biosimilars have been dispensed. In addition, pharmacists generally will not be allowed to dispense interchangeable biosimilars if the prescribing physicians have expressly indicated on prescription forms that the originator brand is to be used.

As with other biosimilars approved in the United States, the FDA has added a suffix to the nonproprietary name; in this case Semglee will be referred to as "insulin glargine-yfgn."

Insulin glargine is a long-acting human insulin analog to enhance glycemic control in adults and pediatric patients with type 1 diabetes and in adults with type 2 diabetes.

Biosimilars are approved by the FDA as having highly similar safety and efficacy to the reference brand and "no clinically meaningful differences." Physicians are free to use them not only for the indication they were expressly approved for, but also for extrapolations for which the original brand has been approved. For example, a bevacizumab biosimilar may have been approved for colorectal cancer, but also may be used for nonsquamous non–small cell lung cancer.

The interchangeable designation is not meant to suggest that interchangeables are superior to biosimilars, but in order to obtain the designation, biosimilar developers generally must perform switching studies that provide evidence that patients who use first the originator or biosimilar and then switch to the other do not experience higher rates of adverse events or decreased efficacy.

Therefore, the interchangeable designation does create the impression that there may be a difference between a general biosimilar and an interchangeable, and some in the biopharmaceutical industry have speculated that interchangeables will create confusion and possibly discourage use of standard biosimilars. In fact, there is some debate among manufacturers about the value of interchangeable status.

The company Alvotech of Reykjavik, Iceland, is banking on interchangeable status for its pending adalimumab high concentration biosimilar (AVT02), which would be the first high concentration adalimumab in the United States. The company has submitted "intention to market" notice that it will market the product in November 2021, but Alvotech is currently entangled in litigation with the maker of the originator (Humira) over patents protecting Humira from competition.

Although they got FDA approval for Semglee in mid-2020, Biocon Biologics and its distribution partner, Viatris (formerly Mylan), have sought biosimilar and interchangeable status for this product separately because they felt it would improve the product's marketability. Because it is the first interchangeable insulin biosimilar to Lantus, the FDA approval gives Semglee 12 months of product exclusivity before the next interchangeable biosimilar to Lantus can be approved, according to Biocon Biologics.

"Commercial preparations for launch are underway," the company said in a statement. “We are extremely proud to be the first to obtain approval of an interchangeable Biosimilar product in the United States. It is a milestone achievement for both Biocon Biologics and our partner Viatris. This will allow pharmacy level substitution and thereby provide convenient and affordable access to Semglee, a quality biosimilar insulin glargine," said Kiran Mazumdar-Shaw, executive chair for Biocon Biologics.

In early 2020, insulins were added to the biologics that are approved under the Biologics Price Competition and Innovation Act approval pathway. There is much debate over whether their approval as biosimilars will help to bring more competition to the insulin market, although that was the intention. Lantus was Sanofi's second best selling pharmaceutical product in 2020 and generated $2.7 billion in worldwide revenue.

"Biosimilars marketed in the United States typically have launched with initial list prices 15% to 35% lower than comparative list prices of the reference products," the FDA wrote.

According to the FDA, interchangeables carry the following criteria:

• The interchangeable is biosimilar to the reference product,
• They produce the same clinical result as the reference product in any given patient.
• There is no greater safety or diminished efficacy risk from switching between the interchangeable biosimilar and the reference product.

In tandem with the approval announcement, the FDA made available 3 fact sheets today for health care providers, and these include a fact sheet about interchangable products. It has also created a Consumer Update about interchangeables for patients and caregivers.

Semglee is used subcutaneously once daily and is distributed in 10 mL vials and 3 mL prefilled pens.

"This approval furthers FDA’s longstanding commitment to support a competitive marketplace for insulin products. The availability of interchangeable biosimilar insulin products can provide more treatment options to patients, potentially lowering treatment costs and enabling greater access for more patients," the FDA wrote.