Preparing for the Near-Term Pipeline of Therapies, and Opportunities for Cost Savings

Increased competition is making its way into the specialty drug market, affecting orphan conditions, cancer types, and even common specialty conditions, which is presenting some cost savings opportunities, explained Aimee Tharaldson, PharmD, senior clinical consultant for emerging therapeutics at Express Scripts, who presented on the specialty pharmaceutical pipeline during her regular session at AMCP Nexus 2019.

Several specialty drugs will be going generic over the next few years, and there is a $34 billion market opportunity for first-time generics for specialty medications over the next 4 years, she explained. There are expected to be generics for the multiple sclerosis drug Tecfidera, which has annual sales of about $3.5 million, beginning in September 2020. At the same time, the market will see first-time generics for Truvada, the pre-exposure prophylaxis for HIV, which has annual sales of about $3 billion.

Biosimilars

Some of the most activity around competition is happening in the biosimilar space. There are 77 patent expirations through 2023, and there is a $62 billion opportunity for biosimilars during the next 4 years. However, the US market is moving slowly. For instance, Tharaldson noted that expectations of 2019 biosimilar launches were optimistic—Enbrel biosimilars now may not launch until 2029.

While there are 29 biosimilars approved for 9 biologics in the United States, only 9 biosimilars for 6 biologics have actually launched:

• Filgrastim biosimilars: Zarxio has gained 17% of the market share, and Nivestym has 34% of the market
• Infliximab biosimilars: the reference product, Remicade, still has 92% of the market share, so these biosimilars have had a more difficult time gaining market share
• Avastin biosimilars: the 1 launched biosimilar has provided a 15% discount to the reference drug's list price
• Herceptin biosimilars: the 1 launched biosimilar has also provided a 15% discount to the reference drug's list price
• Epogen/Procrit biosimilar: Retacrit has about 22% of the market
• Neulasta biosimilars: these 2 biosimilars, Udenyca and Fulphila, only have about 18% of the market, but they are priced at more than a 25% discount to Neulasta

There are a variety of reasons why products may not have launched yet, including patent protections, patent litigation, or simply the decision not to launch, according to Tharaldson. There are potentially 3 more biosimilars that can be approved by the end of the year. One of them, Pfizer’s Humira biosimilar, will not launch until 2023.

Currently, biosimilars are acting as a competing brand class. She noted that biosimilar manufacturers face many legal hurdles, and once they make it to market, they are having a difficult time capturing that market.

“But eventually are going to lead to significant cost savings,” Tharaldson said. “So, in just a little over 3 years, we’re going to have multiple biosimilars to Humira, which is an $18 billion per year drug, so that’s going to help lower spend in many therapy classes.”

Cancer

While there are 1.7 million new cases of cancer diagnosed each year, the death rate has dropped 25% since 1991. However, there was a big dip in approvals with only 8 so far in 2019 compared with 17 novel cancer drug approvals in 2018.

There are more than 100 types of cancer, with breast cancer being the most common in women and prostate cancer being the most common in men. Of the cancer drugs in the pipeline pending approval, 4 are breakthrough therapies:

• Avapritinib, an oral kinase inhibitor to treat PDGFRA exon 18 mutation in gastrointestinal stromal tumors. In addition to being approved for patients with the mutation, there could be a second indication for fourth-line use after other options.
• Zanubrutinib, a Bruton tyrosine kinase inhibitor to treat relapsed or refractory mantle cell lymphoma in patients who progressed on other therapies.
• Enfortumab vedotin, an antibody-drug conjugate targeting Nectin-4 to be used as a third-line treatment in advanced urothelial cancer. The early data had a 44% overall response rate, although 12% of patients discontinued therapy due to adverse events.
• Trastuzumab deruxtecan, an antibody-drug conjugate targeting HER2 in patients who with HER2-positive metastatic breast cancer who had previously been treated with at least 2 previous anti-HER2 therapies. It is also being looked at for other HER2 cancers, like gastric, lung, and colon cancers.

In the near-term pipeline, there are 8 breakthrough therapies, including 2 chimeric antigen receptor (CAR) T-cell therapies: idecabtagene vicleucel from bluebird bio to treat multiple myeloma and lisocabtagene maraleucel from Celgene to treat diffuse large b-cell lymphoma.

Gene Therapies

There are more than 600 cell and gene therapies in the pipeline. These therapies modify a person’s genes either by replacing disease-causing genes, inactivating disease-causing genes, or introducing new or modified genes.

Currently there are only 6 approved: 4 immunotherapies (2 of which are CAR T-cell therapies) and 2 gene replacement therapies. Another 9 could be approved in the next year, including 4 cancer immunotherapies, 3 gene replacements for rare conditions, and 2 gene replacements for hemophilia.

Nonalcoholic Steatohepatitis

There are 13 drugs to treat nonalcoholic steatohepatitis (NASH) in the near-term pipeline and only 1 that is currently pending approval. Patients with NASH have fat in the liver, liver inflammation, and liver damage. It is the fastest growing cause of liver cancer and transplant, and an estimated 6 to 16 million Americans have NASH. These patients also tend to have other comorbidities, such as high cholesterol, type 2 diabetes, insulin resistance, and obesity.

“There’s nothing specifically approved to treat these patients,” Tharaldson said. “They just need to lose weight and eat healthy and exercise and avoid alcohol.”

Most of the drugs in development for NASH have different mechanisms, and the standard of care will likely be some kind of combination therapy, she noted.

Obeticholic acid is the drug expected to be approved first. A study showed that it improved liver fibrosis with no worsening of NASH in 23% of patients versus 12% in the placebo group. It is expected to be approved in May 2020.

It is currently on the market to treat a rare condition with a $70,000 a year price tag; NASH is a much larger patient population, so “it’s going to be interesting to see how this is priced.”

Other drugs to treat NASH will come out later. The next treatment may be approved in late 2020, but phase 3 data hasn’t come out yet. After that there are 3 potentially in 2021 and 5 in 2022 or later.

The NASH market has the potential to be quite large, with costs of $20 billion or more a year. However, there remain a lot of unknowns, and there have not been a lot of positive phase 3 data as of yet. In addition, there need to be other ways to identify patients with NASH other than through biopsy, which is expensive and invasive.

Cost is also a big unknown. Some estimates have put these therapies in the range of $3000 to $6000, like a statin or diabetes medication, but there are other estimates that place the cost of these therapies much higher at $70,000 a year.

Finally, identifying patients with NASH remains a challenge. There need to be other ways to identify them other than a liver biopsy, which is not only expensive but invasive.