Patients suffering from one of the many hundreds of rare diseases known to exist have a better chance than ever of finding a treatment. Companies large and small continue to invest, given high unmet need and very targeted populations. Progress must continue: many conditions remain un- and under-diagnosed, and many more are therapy-less. Yet the growing number of new approved therapies must now be accompanied by creative approaches to paying for them.
Sanofi in early February secured expedited US approval for Cablivi (caplacizumab), which treats acquired thrombotic thrombocytopenic purpura (aTTP), a rare and often fatal disease characterised by unwanted blood clotting. The compound came to Sanofi via the French group’s $4.8 billion acquisition of nanobody company Ablynx in January 2018.
Patient numbers for individual conditions may be small (TTP is thought to affect fewer than four out of every million people; aTTP even fewer). But the dollars involved are not. Sales of drugs designated as treating orphan diseases – nowadays including most targeted cancer treatments – can reach many billions. Merck’s Keytruda (pembrolizumab) is the poster child of blockbuster orphans. Its 2019 estimated annual sales are between $7-9 billion, thanks to its suite of (mostly orphan-designated) approved indications. The price tags for such orphan drugs are attractive for developers, too – and more than make up for the low volumes. Keytruda costs more than $13,000 per month in the US, though actual prices, and those in other markets, vary widely.
Hence rare diseases are now, collectively, a popular franchise for even the largest Big Pharma. Sanofi, Novartis and Takeda, which underwent a $46 billion merger with rare-disease-focused Shire in 2018, are also leaning increasingly on orphan treatments to boost growth amid patent expiries and declining sales of older, more mass-market drugs. Novartis in April 2018 bought AveXis for $8.7 billion, keen to access a late-stage gene therapy candidate for spinal muscular atrophy (SMA), and a broader gene therapy platform. The SMA therapy replaces the defective gene that is the root cause of the disease, meaning it may become a one-time treatment. It was filed for US approval in October 2018.
Novartis was already a rare disease player before the AveXis deal: its pioneering CAR-T therapy, Kymriah (tisagenlecleucel), is an orphan drug used to treat various kinds of aggressive blood cancers. The treatment is very expensive – at about $400,000 – and highly complex, and time-consuming, to administer. (It involves extracting patients’ T-cells, a kind of white blood cell, engineering and re-infusing them.)
New and complex treatment classes like gene- and cell-therapies often address rare diseases, because these may result from defects in a single gene or group of genes, and/or are sufficiently serious to warrant higher-risk, less well-tested approaches. Spark Therapeutics’ approved gene-therapy Luxturna (voretigene neparvovec) treats a rare inherited retinal disease. Amgen’s oncolytic virus Imlygic (T-VEC) has orphan designation for a kind of skin cancer. There are multiple other similar therapies across the industry development pipeline – next-generation CAR-T therapies, checkpoint inhibitors, oncolytic viruses, gene therapies and more. Many have, or will have, orphan designation for increasingly narrowly-defined (sometimes genetically-defined) indications.
These advances are great news for patients. Such programs remain risky individually, but Big Pharma can absorb set-backs more easily than most biotechs. Nasdaq-listed Solid Biosciences saw its shares plunge more than 70% in early February when it got the dosing wrong in a Phase I/II study of gene therapy candidate for Duchenne muscular dystrophy. Yet biotech teams are still diving in: Axovant Sciences is reinventing itself as Axovant Gene Therapy after the failure of its initial strategy – polishing up discarded small molecule drugs (which had pulled in a cool $2 billion from investors).
Eventually, this wave of actual and potential blockbuster-orphans may force new ways to pay for drugs. These therapies are worth their weight in gold to individual sufferers and their families. But as they grow in number, they will place an increasing burden on health systems. Novartis, Spark and others have already engaged in outcomes-based deals, though these remain the exception. Amid a wider and louder drug pricing debate, it is in all parties’ interest to ensure that risk-sharing and other value-based payment approaches, like rare disease treatments themselves, become the rule.