Pharming Group NV, a Dutch biotech company that uses the milk of so-called "magic rabbits" to make its lead product Ruconest, intends to broaden the medicine's use beyond a rare genetic disease to address a market worth some $5.6 billion, piquing the interest of Big Pharma, according to analysts.
Ruconest was approved five years ago by U.S. regulators to treat hereditary angioedema, or HAE, a rare protein deficiency disorder that affects about 7,000 patients in the U.S. and is characterized by debilitating attacks of swelling in the organs, airways, hands or feet.
Administered via intravenous injection for acute episodes, Ruconest contains a recombinant protein that is produced in the milk of transgenic rabbits. These lactating animals are housed in a controlled environment in the Netherlands where they are used as a type of bioreactor, said CEO Sijmen de Vries. One cup of milk per day extracted from these magic rabbits provides enough protein to make one and a half doses of Ruconest. The Leiden, Netherlands-based company now intends to extract the protein from the milk of cows, given that 350 rabbits can produce the same amount as one cow, as it seeks to expand into other indications.
Having turned a profit for the first time ever in 2018 thanks to rising sales of Ruconest in the U.S. and in Europe, Pharming is also exploring new ways of delivering the medicine, ranging from a micro-needle skin patch to painless EpiPen-type administration, in order to make the dosing more convenient. De Vries hopes to expand the use of Ruconest to treat pre-eclampsia, a condition that affects 3% of women in pregnancy and for which there is no cure, and acute kidney injury — also known as contrast-induced nephropathy.
"We believe Pharming fits the profile of a company that Big Pharma is looking for, with an orphan drug product on the market (Ruconest for HAE) that validates the platform technology, which is now being applied to multiple protein-based deficiencies," said Stifel analyst Max Herrmann. There are multiple other protein deficiency disorders that Pharming could apply its technology to, Herrmann added, notably Pompe, Fabry and Gaucher's diseases — all of which are rare diseases known as lysosomal storage disorders, and represent a global market opportunity worth some $5.6 billion in 2017.
People with HAE are unable to make C1 esterase inhibitor, which is the handbrake of 90% of human inflammatory processes, including most of those that involve fatal cytokine storms, said CFO Robin Wright. As a consequence, sepsis, kidney injury and meningitis are all potential further indications for Ruconest.
"In a cytokine storm situation — such as is caused by pre-eclampsia, contrast-induced nephropathy, kidney injury, meningitis, sepsis — the pro-inflammatory molecules just swamp any production of C1 that is meaningful," said Wright. "So you have to supply if you want to treat it. The idea is if you supply lots of C1 early on, you can slow that storm down, so that it doesn't cause so much damage and ideally doesn't kill the patient. All of these indications are linked by that fundamental concept."
Affecting some 1 in 10,000 to 50,000 people across the world, rival products to treat HAE include Shire PLC's Cinryze, which was approved in 2008 and priced at $350,000 per year. Manufacturing issues for the rival plasma C1 inhibitor saw many patients switching to Ruconest last year, helping to drive the €25 million profit made by Pharming in 2018. Another competitor in the space is CSL Ltd., which has an under-the-skin medicine for HAE. Five of the top 20 most-expensive drugs in the world are for HAE.
Despite the availability of clinically and commercially viable competitor medicines for HAE, many of these treatments are produced in a type of hamster ovary cell called CHO, which can result in safety and tolerability issues and black box warnings from the U.S. Food and Drug Administration, said Stifel's Herrmann. Pharming intends to capitalize on this opportunity by expanding and facilitating the use of Ruconest.
"Since we developed the product, the world has moved on and realized that that molecule is absolutely crucial in a whole host of other indications," CFO Wright said.
Sijmen de Vries
"Having demonstrated the viability of producing recombinant proteins in the milk of transgenic rabbits through the global approvals and launches of Ruconest to treat HAE, the company is seeking to expand its Ruconest franchise into new therapeutic areas while turning the handle once more on its platform," said Stifel's Herrmann. "With particular reference to Sanofi's $4.8 billion acquisition of Ablynx NV, we believe Pharming has the right M&A target attributes that are unlikely to continue to go unnoticed."
"Our entire raison d'etre is transgenic animals," said de Vries.
"It's a very powerful platform."
Baby Verma contributed to this article.