Biosimilars, Orphan Drugs Headline Market Trends to Watch in Specialty Drug Pipeline

Biosimilar competition and the development of orphan and cancer drugs were key market trends mentioned by Aimee Tharaldson, PhD, senior clinical pharmacist of emerging therapeutics at Express Scripts, during her keynote address on the upcoming pipeline of specialty drug approvals at the Academy of Managed Care Pharmacy (AMCP) Nexus 2022 meeting.

The next few years will see significant opportunities for biosimilars, noted Tharaldson, with 103 patent expirations through 2025. Not all generics whose patents are set to expire have biosimilars that are in development or FDA approved, and patent litigation may further slow this market impact, she said, but an estimated $71 billion opportunity underlies the approval and integration of biosimilar drugs.

“According to Amgen’s biosimilar report that was released yesterday, biosimilars resulted in $21 billion in savings over the past 6 years, and just in the second quarter of this year alone, savings on drug spend with biosimilars was $3.2 billion,” Tharaldson noted.

A total of 39 biosimilars have been approved by the FDA for 9 different reference biologics, of which 23 are now currently available on the market. Furthermore, 10 biosimilars are expected to enter the market next year for adalimumab (Humira), including one that has achieved interchangeable status (Cyltezo) and at least 4 others seeking this designation.

Additional first-time biosimilar launches are expected within the inflammatory disease market, the leading class of specialty drugs by per-member per-year spending ($199), said Tharaldson, as well as in multiple sclerosis (reference product, Tysabri) and certain eye disorders such as wet age-related macular degeneration (reference product, Eylea).

Within the pipeline of novel specialty drugs pending approval, nearly half (49%) are in development for orphan conditions. And when including orphan cancer drugs, a projected 80% of specialty drug development right now is for orphan conditions and cancer.

“Approximately 7000 rare diseases affect between 25 to 30 million Americans—of these known rare diseases, 95% have no treatment,” Tharaldson explained.

Last year saw a record number (40) of specialty drug approvals by the FDA, accounting for 75% of all drug approvals. A total 22 novel specialty medications have been approved by the FDA this year, with 16 more expected before the end of 2022.

Tharaldson further reviewed 6 specialty therapy classes that could yield new approvals in the coming years, along with gene therapies and specialty drugs of other diseases pending approval. New and emerging cancer therapeutics were not addressed in the discussion, with a separate oncology pipeline session taking place on Friday.

Inflammatory

The leading class of specialty drugs will see a variety of novel therapeutics entering the market, including tumor necrosis factor inhibitors, other biologics, and targeted synthetic disease-modifying antirheumatic drugs (DMARDs).

Already approved for atopic dermatitis, upadacitinib (Rinvoq) is expected to be approved on November 7, 2022, for an expanded indication in axial spondyloarthritis. Next year will see 6 upcoming potential approvals for new and expanded indications in diseases such as alopecia areata (ritlecitinib), plaque psoriasis (bimekizumab), and ulcerative colitis (UC) (mirikizumab). Risankizumab-rzaa (Skyrizi) is also expected to be approved in 2024 for UC.

Atopic Dermatitis

Tharaldson spoke separately on atopic dermatitis (AD), another inflammatory condition that is expected to see 3 drug approvals in the next 2 years. Lebrikizumab, an IL-13 inhibitor, could be approved as early as 2023 for patients 12 years and older with moderate to severe AD, with etrasimod and rocatinlimab also coming up for potential approvals in 2024.

The Janus kinase inhibitor baricitinib (Olumiant) was also mentioned, as Tharaldson noted that it will most likely not be developed for AD despite previously being listed for a potential approval in 2023.

Multiple Sclerosis

Ublituximab is expected to be approved for multiple sclerosis on December 28, 2022, but the majority of other specialty drugs for this disease class are not expected to enter the market until potentially 2024 and 2025. These include evobrutinib, tolebrutinib, fenebrutinib, orelabrutinib, and remibrutinib, all of which are Bruton tyrosine kinase inhibitors.

HIV

With at least 95% adherence needed to maintain viral suppression among patients with HIV, the market is dominated by once-daily regimens. Upcoming potential approvals show another daily oral drug in islatravir, which is used in combination with oral doravirine and is expected to be approved in 2025.

More near-term treatment options seeking approval include potentially the first long-acting HIV-1 capsid inhibitor for the disease, lenacapavir, that is expected to be approved on December 27, 2022. Leronlimab is also projected for approval in 2024, but did recently receive a warning letter from FDA’s Office of Prescription Drug Promotion regarding a promotional video created for the drug by the manufacturer CytoDyn.

Pre-exposure prophylaxis (PrEP) usage is also on the rise, with about 25% of eligible patients prescribed the drug in 2020 compared with only 3% in 2014, said Tharaldson.

Nonalcoholic Steatohepatitis

As the third-leading cause of cirrhosis and the fastest growing cause of liver cancer and liver transplant, the treatment pipeline for nonalcoholic steatohepatitis (NASH) has remained largely similar to that listed in the presentation given by Tharaldson last year.

The most near-term drugs potentially coming in 2023 include resmetirom and obeticholic acid, the latter of which was issued a complete response letter from the FDA saying that based on the available data, the potential benefits of the drug do not outweigh the risks. The manufacturer for obeticholic acid plans to resubmit its application for approval later this year, she said.

Other drugs in development for NASH have target dates for potential approval that may change, but they include aramchol in 2023, cilofexor and firsocostat in 2024, and belapectin and semaglutide in 2025.

Alzheimer Disease

As the population continues to age, prevalence of Alzheimer disease, a progressive brain disease predominantly affecting those 65 years and older, is on the rise as well and is expected to double within 30 years, cautioned Tharaldson. Aducanumab (Aduhelm) was the first drug approved for Alzheimer disease in 18 years—with notable controversy—and its outcomes data are expected to come in 2026.

Additional potential biologic DMARDs in the development for the disease include 3 anti-amyloid beta antibodies, lecanemab, donanemab, and ​​gantenerumab, with expected approval dates in 2023 and 2024, and an anti-tau antibody (semorinemab) that is projected for approval in 2025 or later.

“There are other companies like Eisai and Janssen that also have anti-tau antibodies in development for Alzheimer disease as well, but it's going to be at least a few years before any of these type of drugs come to market,” she said.

Hemophilia

Gene therapies play a large role in the specialty drug pipeline for hemophilia, with 8 different therapeutics under development for potential approvals through 2025. Next month may see the approval etranacogene dezaparvovec for hemophilia B, which has shown in phase 3 clinical trial data to reduce all factor IX–treated bleeds by 77% over months 7 to 18.

Efanesoctocog alfa and valoctocogene roxaparvovec, a long-acting factor VIII and a gene therapy, respectively, both for hemophilia A, could also be approved in 2023.

Gene Therapies and Other Select Specialty Drugs

More than 500 gene and cell therapies are in the pipeline for specialty drug approval, with this market projected to generate $25 billion per year by 2034. Next year will see potential specialty drug approvals for rare diseases such as eystrophic epidermolysis bullosa, duchenne muscular dystrophy, and β thalassemia/sickle cell disease.

Tharaldson concluded the session by reviewing select specialty drugs pending approval in the near term that were not yet mentioned:

• Pending approval in 2022: cipaglucosidase alfa in Pompe disease, sparsentan in immunoglobulin A (IgA) nephropathy, teplizumab as a preventive therapy in type 1 diabetes, and palovarotene in fibrodysplasia ossificans progressiva
• Pending approval in 2023: tofersen for SOD1-positive amyotrophic lateral sclerosis, daprodustat for anemia of chronic kidney disease, trofinetide for Rett syndrome, velmanase alfa for alpha mannosidosis, and leniolisib for activated phosphatidylinositol 3-kinase delta (PI3Kδ) syndrome