Is pharma’s interest in orphan drugs waning?

For many years, orphan drugs for rare diseases have been a draw for pharma companies, offering high prices, swift regulatory reviews, and often extended marketing exclusivity – but there are signs they may be losing their allure.

A new analysis by Evaluate has found that, while there is still plenty of interest in the category, sales growth is starting to level off and being caught by non-orphan drugs, in part because of a resurgence of effort in widespread diseases like obesity and immunological and neurological disorders, such as multiple sclerosis, depression, and anxiety.

Payers may also be focusing more on big health challenges at the population level, rather than rare conditions, and have started to baulk at the premium pricing for orphan drugs, according to Evaluate’s 2024 Orphan Drug Report.

The analysis notes that orphan drug sales growth averaged almost 11% annually in the 10 years to 2023 – reaching a market value of $168 billion worldwide – but will “barely make double digits” for the rest of the decade.

That’s still a healthy rate of growth, of course, resulting in an estimated market value of almost $270 billion in 2028, and Evaluate says that the slowdown in the orphan category is relative, retaining roughly the same proportion of the overall prescription medicines.

“High prices, small trials, well-defined populations and development incentives continue to buoy this important sector. So does regulators’ flexibility in offering expedited market access for drugs addressing unmet needs,” according to the report, which notes that almost 60% of the FDA’s new drug approvals in 2023 were for orphan drugs.

The category will remain a strategic priority for pharmaceutical companies for good reason, given that the top 10 orphan drugs will collectively generate more than $57 billion in 2028, according to Evaluate.

It predicts that the top three sellers in that year will be Johnson & Johnson’s blood cancer drug Darzalex (daratumumab), Vertex’s Trikafta (elexacaftor/tezacaftor/ivacaftor) for cystic fibrosis (CF), and Roche’s Hemlibra (emicizumab) for haemophilia A treatment, retaining their current podium positions.

There will be some new products among the lower end of the list, however, with big gains expected for Incyte and Novartis’ Jakafi (ruxolitinib) for myelofibrosis, Johnson & Johnson’s Carvykti (ciltacabtagene autoleucel) for bone marrow cancers, and BeiGene’s Brukinsa (zanubrutinib), supplanting AbbVie’s big-selling Imbruvica (ibrutinib) on the top 10 list after besting it in a comparative trial. The full list can be viewed here.

When it comes to pipeline prospects, Evaluate thinks the top five are Vertex’s VX-121 triple for CF, J&J’s nipocalimab with potential across a range of inflammatory and autoimmune diseases, Intellia Therapeutics’ NTLA-2002 for hereditary angioedema, and cancer drugs paltusotine from Crinetics Pharma and bemarituzumab from Amgen.

“Even with the anticipated moderation in growth, orphan drugs continue to punch above their weight class in terms of value,” said Daniel Chancellor, director of thought leadership at Evaluate.

“It’s not surprising that we’d see this moderation as orphan drugs become a mainstream business,” he added, pointing out that the category was only a little behind the value of the oncology market, which was worth $194 billion last year.

One factor that needs to be considered, however, is the Inflation Reduction Act (IRA) in the US, which Evaluate predicts could have an “outsized effect” on orphan drugs. For example, Imbruvica came into the picture for Medicare pricing negotiations because it has multiple indications, so cannot claim the IRA exemption for single-indication orphan drugs.