Orphan Drugs: Finding a Home with Patients
With some 7,000 known rare diseases out there, the orphan drug model makes a lot of sense for certain companies, with certain
infrastructures in place. The big three orphan categories—or the three where drugs and clear investment opportunities exist—are
enzyme replacement therapies (ERT), which is the biggest, followed by pulmonary arterial hypertension (PAH), and hereditary
In October, Schwartz of Leerink Swann published an extensive report entitled "Future of Orphan Drugs: The Golden Child of
Biotech." He discussed two of his favorites with Pharm Exec.
The first is a Biomarin ERT therapy for Morquio A syndrome (MPS IVa), an inherited disease caused by a deficiency of the lysosomal
enzyme, N-acetylgalactosamine-6 sulfatase, or GALNS. MPS IVa symptoms include skeletal dysplasia, short stature, and joint
abnormalities, which limit mobility and endurance. The disease often leads to shortened life expectancies, and is estimated
to occur in 1 in 200,000 live births. There isn't currently a treatment for MPS IVa, but GALNS would supply the lacking enzyme,
Unlike Biomarin's ERT therapy Naglazyme, for the related Maroteaux-Lamy syndrome (both are mucopolysaccharidosis diseases),
GALNS won't have to compete with bone marrow transplant, because it hasn't been shown to be helpful for MPS IVa, so Biomarin
would have the only treatment. Biomarin's drugs are "basically annuities that grow ad infinitum, because there are always
new patients being born with this disease, and there's going to be no change to the pricing and reimbursement model," says
Schwartz. "The patients are on it for life." One of the benefits of ERT therapies is that they are "some of the most highly
glycosylated products, with a lot of post-translational modifications that make it really difficult for biosimilars to replicate
to FDA's satisfaction," he notes. Schwartz likes Biomarin because the company "should get exponential operating leverage on
their model, because they'll go to essentially the same geneticists who treat MPS I, VI, IV and Pompe patients ... they don't
necessarily need more sales reps." Schwartz says the GALNS ERT could be a blockbuster eventually; Biomarin is expected to
announce Phase III data in late 2012. If that seems far-out, consider the fact that orphans "tend to advance more rapidly
than a mass-market drug." Leerink Swann forecasts global sales of around $550 million in 2022, and Schwartz describes it as
a "miniblockbuster," adding, "you don't need a blockbuster to move the needle on one of these orphan models ... but you could
string a few [orphans] together and have a good portfolio."
United Therapeutics Corp. (UTC) is another of Schwartz's favorites, particularly the company's PAH treatment, an oral form
of Remodulin (treprostinil). The company already markets an injectable form of Remodulin, and an inhaled form, called Tyvaso.
For the treatment of PAH, "it has been a two-company duopoly forever," with UTC's Remodulin and Tyvaso on one side, and Actelion's
Tracleer on the other. Gilead has made inroads against Tracleer with Letairis (ambrisentan), a once-a-day oral tablet. Schwartz
says Gilead's drug won't impact oral Remodulin, because treprostinil is a protocycline, and protocyclines have a "lot of beneficial
effects on certain cell types and PAH, and they're vasodilatory"—meaning they have anti-platelet properties—"but they are
very hard to administer." UTC will file with FDA in the first quarter of 2012, says Schwartz, adding that oral Remodulan (aka
UT-15C) "has been termed the holy grail by some pulmonologists, that would like to see more of their patients on protocycline
therapy, which is considered by some to be the optimal drug for PAH."
UTC's oral Remodulan has produced mixed data to date, and the stock is hovering at near-lows, but Schwartz is unmoved. "These
were the same concerns before the inhaled form [Tyvaso] was approved, and it's selling like hotcakes." Schwartz projects a
modest $250 million way out in 2025, but says that these drugs "generally outsell their data."