Novartis trims its pipeline

With sales of a key product, Leqvio, still sluggish, Novartis needs its much-maligned pipeline to be firing on all cylinders. But today the group slipped out several project discontinuations and delays in a fourth-quarter earnings report best described as mixed.

Perhaps most worrying to investors will be hints that all is not completely rosy with iptacopan, one of Novartis’s big R&D hopes. But there were also discontinuations for the Huntington’s hopeful branaplam, and Piqray in new indications recently highlighted as promising.

During the group’s fourth-quarter earnings call today its chief executive, Vas Narasimhan, said more cuts to the pipeline would come as Novartis starts “to prune out non-core areas” and focuses on quality over quantity.

Iptacopan delays

Iptacopan has already prevailed in its lead indication, paroxysmal nocturnal haemoglobinuria (PNH), but a raft of other uses are coming behind.

At least one of these is now a dead end. Novartis disclosed that it had dropped the oral complement factor B inhibitor in membranous nephropathy, where it was in phase 2.

The sellside had not pencilled in any forecasts for this indication, so Novartis should be able to brush the setback off. More concerning could be delays in IgA nephropathy and C3 glomerulopathy, where analysts expect 2028 sales of $112m and $305m, according to sellside consensus compiled by Evaluate Pharma.

Trial recruitment has been slow, delaying expected submissions by a “few months”, but Novartis still expects pivotal data in both uses this year, in line with previous guidance. But timings in atypical haemolytic uraemic syndrome have been pushed back, with results from the Appelhus trial now due in 2025, back from 2024 previously.

While iptacopan could still succeed in these uses, the pace of recruitment might provide a note of caution to those expecting strong demand for oral complement-targeting projects.

And Mr Narasimhan admitted that, in PNH, the iptacopan launch would "not be fast” given the strength of incumbent products – presumably a reference to Astrazeneca’s Soliris and Ultomiris.

Piqray and branaplam blows

While iptacopan is Novartis’s most valuable pipeline prospect by some distance, the group also highlighted its approved breast cancer drug Piqray as one to watch at an analyst day last September. Specifically, the company flagged studies in the new uses of triple-negative and Her2-positive breast cancer.

Now these have fallen by the wayside, with Novartis saying the move would help it prioritise “other key programmes”. Epik-O, a phase 3 study in ovarian cancer, continues.

Meanwhile, the loss of branaplam from the Huntington’s pipeline will be a blow in a disease that has seen many failures. This was not entirely unexpected, following a pause in the Vibrant-HD study last summer after signs of side effects.

This looks like bad news for PTC’s similarly acting project PTC518; in October, enrolment into the US portion of the phase 2 Pivot-HD trial of that asset was paused, with the FDA requesting more data. The most advanced Huntington’s candidate is Prilenia’s pridopidine, with data from the phase 3 Proof-HD trial expected this quarter.

Perhaps Novartis should have culled branaplam sooner. It abandoned the project in spinal muscular atrophy in 2021, but this was down to competition from existing agents; Huntington’s is a very different beast, with no treatments available.

Knowing when to stick and when to call it a day in future will be key if Novartis is to move away from its current status as a company with a lot of approved products but a dearth of valuable ones.

The table in this story has been updated to clarify that iptacopan C3G data are due in 2023.