Keeping an Eye on Increasing Competition in the Specialty Drug Pipeline

With all of the changes in the pharmaceutical development landscape from year to year, there is at least 1 constant: Aimee Tharaldson, PharmD, will be on hand to make sense of the specialty drug pipeline and its implications for the managed care market. As she does every year, Tharaldson, senior clinical consultant in emerging therapeutics for Express Scripts, presented her look at the development pipeline to a crowded room at the Academy of Managed Care Pharmacy Annual Meeting, held March 25-28 in San Diego, California.

She explained that her assessment of the specialty drug pipeline could be distilled into 3 broad themes: increased competition, cancer drug development, and orphan drug development.

More competition will result in more opportunities for cost savings, said Tharaldson, with many specialty drugs going generic in the next few years and biosimilar approvals increasing. About $24 billion in opportunity lies within the group of specialty drugs that have upcoming generics through 2023, compared with $14 billion in the 2015-2018 period.

In the biosimilar landscape, she noted that, although 18 have been approved, 7 are still pending a launch, mostly due to patent litigation. These biosimilars often have limited indications compared with the reference drugs because some of the originators’ indications are still protected by orphan drug exclusivity. The impact of legal hurdles is exemplified by the uncertainty around the launch of the etanercept biosimilar Erenzi. If a court rules in favor of the biosimilar’s maker, Sandoz, it could hit the market as soon as this year; if Amgen, which makes the reference Enbrel, succeeds, the biosimilar’s entry could be delayed until 2028 or 2029.

Even though some biosimilars have struggled to capture market share, Tharaldson foresees significant cost savings opportunities in the coming years, especially with 8 biosimilars pending approval this year and new FDA policies encouraging biosimilar development and providing more clarity around naming conventions.

Relating to the second trend of cancer drug development, Tharaldson noted that, despite the FDA approving a record 17 new cancer drugs in 2018, there hasn’t been a subsequent reduction in cost—many of these drugs launch at around $150,000 per year.

Orphan drug development represents a particularly lucrative segment, as the costs of these drugs are 5 times those of other drugs; 30% are considered “blockbusters,” indicating more than $1 billion in sales. In the specialty pharmacy pipeline, 53% of drugs are for orphan diseases.

In terms of the 4 specialty drug approvals so far this year, Tharaldson said 2019 was off to a “slow start” but that the drug mechanisms and disease states covered by these approvals represent promising strides in areas without many alternatives. For example, brexanolone (Zulresso) treats severe postpartum depression, which affects 11% of new mothers, and starts working within 48 hours compared with oral antidepressants that may take weeks to show effects. The breakthrough therapy esketamine for treatment-resistant depression is related to the illegal party drug ketamine, so its distribution and use will be monitored carefully, but it could help reach the large market of about 5 million patients who don’t respond to depression treatments.

Looking ahead to the upcoming pipeline, Tharaldson discussed 7 classes of specialty drugs to keep an eye out for.

• Inflammatory disease. These drugs to treat diseases like rheumatoid arthritis and ulcerative colitis are the leading class by per-member-per-year spending. With the 5 upcoming drugs targeted for approval in 2019 or 2020, we will see indications expand and competition increase in this market, especially as new products are demonstrating improvements over existing drugs in clinical trials.
• Multiple sclerosis. Five new oral drugs (4 in 2019 and 1 in 2020) will potentially join the disease-modifying drugs on the market. Four of them treat the relapsing form of the disease and the other is for secondary progressive multiple sclerosis. These new agents offer improved safety profiles compared with existing drugs.
• Oncology. Of 8 cancer drugs pending approval in 2019, 7 are oral and 1 is intravenous; these drugs will treat a range of cancer types from urothelial cancer to solid or giant cell tumors to myelofibrosis. Some are breakthrough therapies, and some apply to patients with specific gene types. They also have different prospects for approval. Tharaldson thought selinexor was unlikely to be approved in July because an FDA panel voted to wait for more data on it, but she said that pexidartinib might be approved even before its August action date.
• HIV. The HIV market is dominated by single-tablet regimens because adherence to antiretroviral therapy is key for achieving viral suppression. One new oral drug could be approved in 2019, and 2020 could see the entry of 1 intramuscular, 1 oral, and 1 subcutaneous drug. The intramuscular injection presents an alternative to daily pill regimens, but the pain associated with injection may limit its uptake.
• Nonalcoholic steatohepatitis. There’s been “a lot of buzz” in this disease class, with many drugs in development, said Tharaldson, who provided a snapshot of the pipeline. Three oral drugs are in phase 3 trials and could gain approval by 2020 and beyond, and there are several more that could be approved later on. Drug manufacturers are drawn to this class because analysts expect it could be a market of $20 billion per year, but “there’s a lot of unknowns at this point…We don’t know what combos are going to be effective and safe, we don’t know long-term clinical benefits of these medications, we don’t know how much they’re going to cost,” she said.
• Alzheimer disease. The search for a drug that can modify the disease course instead of temporarily improving symptoms has suffered disappointing setbacks, but there are prospects on the horizon. Three drugs that affect antiamyloid-β antibodies are in the pipeline and could be approved in 2021-2022 and beyond, whereas drugs acting on anti-τ antibodies would take even longer. “It’s gonna be several years, unfortunately, before we see disease-modifying drugs available,” Tharaldson said.
• Hemophilia. With 7 drugs in the pipeline that could be approved from 2020 to 2022, Tharaldson sees opportunity in the early promising results of gene therapy via 1-time infusions, which seem to be well tolerated and could potentially eliminate the need to use clotting factors.

Some other interesting drugs in the pipeline with approvals expected within the first half of 2019 included the breakthrough therapy onasemnogene, a 1-time intravenous infusion for treating the highly fatal disease type 1 spinal muscular atrophy in babies. Videos of improvements in treated patients have been “very impressive,” said Tharaldson. She thought the drug has a chance of being approved before its May action date.

Tharaldson also mentioned 4 therapies—tafamidis, afamelanotide, fenfluramine, and golodirsen—that could be approved later in the summer.