While Ruconest in its current iv formulation could work on a preventative scale, it would also cost north of $700,000 dollars per year, and de Vries said the company was not keen on doing this “to the system or the patients”. However, an intradermal or subcutaneous version of Ruconest approved for prophylaxis could be delivered at a very different price point which would make a lot more sense than acute therapy on its own.
Fortunately, Pharming's Phase II prophylaxis study with the approved version did not have the data richness the FDA was looking for to proceed with a prevention indication. This “solved a problem” for a company keen to stick to its strategy of developing its new administration routes, which also include intramuscular (Phase I for use in the acute setting as a more convenient option).
Expanded Indications
But it has other plans for the product too. While gaining a bigger seat at the HAE table is a priority for the group, what is “even more exciting”, according to de Vries, is its potential in other indications that could benefit from a C1 esterase inhibitor, said Wright and De Vries, describing C1 as the “body’s own handbrake.”
PHARMING CFO ROBIN WRIGHT
Pre-eclampsia and contrast-induced nephropathy are Pharming’s immediate focus because of the unmet medical need, with both of these indications being potential blockbusters for the company.
In developed countries, about 3-4% of pregnant women develop pre-eclampsia, with cases totalling around two and a half million a year, with each of those patients needing 10-12 weeks of treatment. “It’s a significant market,” said de Vries, “compared to anything like HAE.” With clinical trials starting in 2019 for both CIN and pre-eclampsia, de Vries hopes that in the long term, this will produce “a very significant upside in what we can produce in sales.”
“We’d have done it earlier if we’d had the money,” said Wright, adding that if the clinical data are not positive in either of these prioritized indications they can be replaced “in a heartbeat” by disease areas such as meningitis or septic shock, which will be taken forward in the future anyway, “as funds allow”.
Resurrected Pipeline In Pompe
Another area of historial interest that Pharming now has the funds to pursue is Pompe and Fabry disease, and it has a alphaglucosidase candidate drug that the company is “jumping up and down to get it ready and into the clinic sometime in the next year,” explained de Vries.
Pharming has history in Pompe disease, partnering with Genzyme Corp. back in 2001. This collaboration ended badly for Pharming when it ran out of money and had to hand the asset to Genzyme to avoid bankruptcy. “Genzyme thought it was a bit too esoteric to continue with the rabbits,” said de Vries. “They thought their own drug reactor would do the job, and it did in their defense, but it is a suboptimal product.”
So Pharming is starting from scratch with an alphaglucosidase from its Transgenic Production Technology Platform. “We already know it is much closer to natural than [Genzyme’s marketed Pompe product] Myozyme and Lumizyme,” said de Vries, explaining that the more natural the product, the less immunogenicity is created in the patient.
“They tend to run perfectly well for about 12-14 weeks and then they become refractorate of the drug,” said Wright. Meaning that only about 15-20% of patients are able to stay on drug for any length of time. “The expanded dose is 500g infusion for six hours every two weeks,” he explained. “So there is a big advantage in having a version that is essentially natural alphaglucosidase, in all probability we will be able to reduce the dose and treat a lot more of the refractory patients, which multiplies the size of the market by several factors.”
Pharming intends to begin a Phase I/II trial for Pompe in the first half of 2019, and for Fabry’s Disease in the second half of 2020.
Everything that Pharming is currently working on will launch after 2020, so it is also looking for an opportunity for additional near-term revenue. It is actively looking to buy in additional assets in rare disease indications. “It’s about leveraging our commercial infrastructure and closing the gap in the pipeline,” de Vries concluded.