- Netherlands-based group Pharming has in-licensed for $20 million an experimental rare-disease drug from Novartis called leniolisib, which is part of a drug class more typically advanced for oncology indications.
- Gilead Sciences' Zydelig, Bayer's Aliqopa and Novartis' Piqray are all PI3K inhibitors from the same class. They each hold U.S. approvals for treating cancer, but have struggled to make a strong impact on the market.
- Pharming will assist Novartis' clinical work in activated phosphoinositide 3-kinase delta syndrome (APDS) and, if successful, commercialize the drug, raising the potential that anti-PI3K drugs might have promise in immune and inflammatory disorders.
Drug developers had high hopes for phosphoinositide 3-kinase (PI3K) inhibitors in cancer a decade ago. These small molecule agents disrupt a key pathway in tumor development, where mutations allow for cell survival and proliferation.
The promise hasn't been borne out, as side effects and disappointing efficacy have sidelined many projects. Three agents from this class, though, have made it through to the market — Zydelig (idelalisib), Aliqopa (copanlisib) and Piqray (alpelisib), the last of which received approval in May.
Gilead's project, approved in lympohma, is the only one for which sales were available. Those were $133 million in 2018, down 11% from 2017 numbers.
Autoimmune and inflammatory disorders are thought to be another potential target for PI3K inhibitors, however, because the protein is also involved in immune response. Pharming's deal shows the biopharma sector is still looking at this option for the class.
It helps that APDS, which affects around one to two individuals per million people, is caused by a mutation in the isoform of PI3K that leniolisib blocks. The resulting disease suppresses production of immune cells, and patients have frequent infections. Novartis first initiated trials in 2015, with a plan to enroll 30 patients.
Pharming says the current trial should be sufficient for regulatory approval. If successful, the drug could be marketed as soon as 2020 or 2021.
In a note to clients, Stifel analyst Christian Glennie wrote that the deal helps to diversify Pharming's product lines away from the hereditary angioedema drug Ruconest (C1 esterase inhibitor) in a way that complements its current sales and marketing efforts. The target specialists of both drugs are immunologists.
Ruconest is a treatment for acute attacks of HAE, and may be under pressure by prophylactic treatments like Takeda's Takhzyro (lanadelumab), so Pharming will need to beef up its product offerings.
Glennie forecasts leniolisib peak sales of $85 million, evidence of the disease's extremely rare nature.