Four years ago, the orphan drug market was predicted to be a huge target for biosimilar entries. The year 2020 represents opportunity for biosimilars as multiple, dominant orphan drug brands lose their exclusivity.

Meanwhile, patent battles continue to play out between established brands and biosimilar competitors, Ann McNamara, PharmD, said in a drug pipeline report for the Specialty Therapies and Biosimilars Congress.

For the rheumatoid arthritis drug infliximab, there are 2 contender biosimilars that have been approved but not launched, and it remains to be seen whether these will hit the market in 2020, said McNamara, director of clinical development for Fairview Specialty Pharmacy of Minneapolis, Minnesota. These are Avsola by Amgen and Ixifi, by Pfizer. They would join already launched biosimilars Renflexis (Merck) and Inflectra (Pfizer).

According to a 2019 October update from Johnson & Johnson (J&J) the originator biologic Remicade notched third quarter sales of $749 million, down 24.1%. J&J attributed the sales decline to biosimilar competition.

No launch date for Avsola has been announced. Pfizer has previously said it would not launch Ixifi in the US market, where it already has Inflectra in the biosimilar space for infliximab. There are, however, other countries where Inflectra has not been launched and these could be candidates for Ixifi, Pfizer has said. The company acquired Inflectra through its Hospira purchase in 2015, which made Pfizer’s strategy for Ixifi moot.

Heavy biosimilar competition is lined up for AbbVie’s originator Humira for rheumatoid arthritis, although the company is pushing back in a patent struggle to protect its exclusivity against adalimumab biosimilars, McNamara noted. Would-be contenders, all of which are FDA approved and slated for 2023 market entry, include Amjevita (Amgen), Hadima (Merck), Cyltezo (Bi), Hyrimoz (Sandoz), and Abrilada (Pfizer), McNamara said.

Humira generated $20 billion in 2018 revenue. Adalimumab biosimilars entered the European marketplace in 2018 and within 6 months had taken a 27.9% share of Humira’s overseas market.

Amgen’s originator etanercept Enbrel also has been the focus of a patent battle. Two key patents were upheld by a US District Court Judge in August of 2019, although one of the plaintiffs, Sandoz, which is attempting to get Erelzi on the market as an etanercept biosimilar, announced intentions to appeal. Samsung’s Eticovo is another approved biosimilar in this space that could launch. Without a reversal of the court’s opinion, market entry could be delayed until 2029, McNamara said.

Patent Expirations

Aldurazyme (laronidase), an enzyme replacement therapy for the treatment of mucopolysaccharidosis type I, an often life-threatening lysosomal disorder, will lose exclusivity this year, as will Kineret (anakinra), a biologic that can reduce the activity of interleukin-1 (IL-1), a key driver of inflammation in autoimmune and autoinflammatory diseases.

Lucentis (ranibizumab), a treatment for “wet” type age-related macular degeneration, among other conditions, also faces patent loss in 2020, McNamara said. The wet age-related macular degeneration market is estimated at $6.9 billion, according toa 2019 report that projected it to reach $10.4 billion by 2024.

Biosimilar competition on this front is coming from Biogen, which has acquired rights to Samsung Bioepis’ SB11, a biosimilar of ranibizumab, as well as SB15, which is a version of aflibercept (Eylea).

In March 2021, Soliris, the branded eculizumab, a treatment for paroxysymal nocturnal hemoglobinuria, goes off patent. The drug had net product sales of $981 million in 2019, up 9% from the previous year and making it a prime target for competition. Amgen is developing a biosimilar of the Soliris product and reported phase 1 trial findings last year.

Although orphan drugs address needs of small patient populations, they can represent quite large dollar totals. Across drug categories, manufacturers are developing biosimilars and generics to carve market share away from established drugs; McNamara said sometimes single brand drugs may see multiple contenders, whose manufacturers may look to distinguish these products through refinements.

Providing an example of this trend, McNamara cited a generic medicine, berotralstat, a BioCryst entry for prevention of hereditary angioedema (HAE), which affects just 1 person in 67,000. “This would be the first oral regimen for prevention [of HAE], the fourth drug on the market for prevention, and the eighth drug for prevention or treatment; so even though it’s a small orphan condition, we’re seeing competition or refinement of products,” she said.

Dysport (abobotulinumtoxinA), a neuromodulator for cosmetic enhancement, also faces patent loss in 2021 and could see biosimilar competition, McNamara said. Mylan hopes to get a biosimilar neuromodulator to market to compete with Dysport and Allergan’s Botox (onabotulinumtoxinA).

Also in the 2021 exclusivity loss category is Roche’s Mircera (methoxy polyethylene glycol-epoetin beta), a protein for the treatment of anemia.