Pharm Exec's 2012 Pipeline Report - Pharmaceutical Executive


Pharm Exec's 2012 Pipeline Report

Pharmaceutical Executive

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 angioedema (HAE).

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, via transfusion.

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."


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