Novartis cast-off gives Pharming a gap-filler

Pharming picks up Novartis’s late-stage PI3K inhibitor and plans to launch it for an ultra-rare disease. How will the competition respond?


While Pharming’s Ruconest continues to hold up well despite headwinds, the company has wasted no time shoring itself up. Today’s $20m acquisition of Novartis’s leniolisib looks like a smart way to bring in a late-stage asset that Pharming will hope simply to plug into its existing rare disease infrastructure.

The project is a PI3K delta inhibitor, so faces numerous development-stage competitors. However, its target indication, activated PI3K delta syndrome, is so rare that there is probably insufficient room for more than one player; Pharming must make the most of its first-mover advantage.

Indeed, only one other PI3K delta inhibitor, Glaxosmithkline’s nemiralisib, is in clinical trials for activated PI3K delta syndrome, according to And the only other clinical-stage project for this condition, which Stifel analysts reckon affects one to two people per million, is rapamycin.

Glaxo’s phase II safety/pharmacokinetics trial of nemiralisib is set to read out next year. Pharming, meanwhile, says leniolisib could be launched in 2021-22 based on Novartis’s ongoing phase II/III trial. This primarily measures safety, with efficacy a secondary endpoint, but Pharming says it is registrational.


The rationale for Pharming is that the group already markets the hereditary angioedema (HAE) drug Ruconest to immunologists, and these same doctors would be expected to prescribe a treatment for activated PI3K delta syndrome.

Ruconest failed to secure a label extension from episodic to prophylactic HAE a year ago. While many thought this would leave it vulnerable, sales keep beating forecasts, suggesting that the group’s rivals, Takeda and CSL, are fighting it out over prophylactic use, leaving Ruconest relatively unencumbered in the episodic setting.

That said, Pharming’s pipeline had a gap between Ruconest and projects for other rare diseases such as Pompe and Fabry’s diseases. This is where it will hope leniolisib can fit in.

Selected PI3K inhibitors with delta subtype specificity
Project Company Indication highlight
Zydelig Gilead Approved for CLL
Phase III
TG-1202/umbralisib TG Therapeutics Oncology
CDZ173/leniolisib Pharming/Novartis Activated PI3K delta syndrome (NCT02859727)
Phase II
Nemiralisib Glaxosmithkline Activated PI3K delta syndrome (NCT02593539)
ME-401 MEI Pharma Oncology
INCB50465/parsaclisib Incyte/Innovent Oncology
HMPL-689 Hutchison China Meditech Oncology
ACP-319 Acerta Pharma Oncology
Phase I
AZD8154 Astrazeneca Asthma
GSK2292767 Glaxosmithkline Asthma/COPD
DS-1515 Daiichi Sankyo Inflammatory disorders
IOA-244 Ionctura Oncology & fibrotic indications
SRX2558 Signalrx Pharmaceuticals Oncology
Source: EvaluatePharma.

Activated PI3K delta syndrome results from a mutation in the PIK3CD gene that increases activity of this kinase subtype, resulting in patients failing to react effectively to infections. A specific PI3K delta inhibitor seems a logical pharmacology approach, though most of the numerous assets in development here target cancer indications.

However, recent thinking is that targeting PI3K alpha is needed for oncology use, leaving delta inhibitors like Gilead’s Zydelig, and pan-PI3K approaches, out in the cold.

Given how incompatible the big pharma model is with rare diseases it is little wonder that Novartis agreed to offload leniolisib for just $20m up front. Glaxo, too, might now be mulling over similar business considerations.

The biggest risk to Pharming is that Glaxo licenses nemiralisib to a powerful rare disease-focused biotech, or that one of the small players currently looking at PI3K delta inhibitors in oncology decides to give activated PI3K delta syndrome a shot. By then, however, it might be too late to compete with leniolisib.

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