Novartis's Pipeline Math Gets Harder as Investors Train Their Sights on the Avidity Bet
Published on 09/18/2026 at 09:11 | Editorial boerse-global.de
A single failed trial is a cost of doing business in pharmaceuticals. A cluster of them inside two weeks starts to look like a pattern — and for Novartis, the pattern has shifted the conversation away from the science and toward the balance sheet.
The Swiss drugmaker has now halted development of lifonebart (VHB937), its TREM2 antibody, in amyotrophic lateral sclerosis. The Phase 2 ASTRALS trial, which enrolled 251 patients in the early stages of the disease, missed both its primary and secondary endpoints at 40 weeks. Novartis confirmed the discontinuation to Reuters but is holding back the detailed data until the ALS/MND symposium in Amsterdam in early December.
That decision lands lifonebart in an already crowded loss column. On September 15, the Phase 2 SEALS study of partner candidate NX210c from Axoltis fell short. Earlier in September, Novartis absorbed two larger blows in quick succession: the Lp(a) lowerer pelacarsen missed its goal of cutting cardiovascular events in the Phase 3 Lp(a)HORIZON trial despite successfully reducing lipoprotein(a) levels, and del-desiran failed in myotonic dystrophy type 1 in the Phase 3 HARBOR study. Those setbacks are now roughly two weeks old, and the stock has clawed back 3.6 percent since.
One Platform, Two Very Different Bets
What separates the ALS news from the September wreckage is scope. Novartis is keeping its Alzheimer's program running on the same TREM2 mechanism, drawing a deliberate line between indications rather than abandoning the platform outright. Management has effectively told the market that the damage is contained — a narrower problem than the earlier wave of failures suggested.
The market's reaction bore that out. The shares barely moved on the ALS disclosure, a stark contrast to the roughly 3 percent slide they took in the wake of the pelacarsen miss. In premarket trading the stock sat at EUR 122.98, essentially flat against the prior close of EUR 122.96.
Should investors sell immediately? Or is it worth buying Novartis?
Zoom out, though, and the picture is less comfortable. At that level, Novartis trades about 15 percent below its 52-week high of EUR 144.30 set in February, and some 7 percent under its 50-day moving average of EUR 132.18. The rebound of the past week has not been enough to reverse the medium-term downtrend.
Momentum data tell a similar story. Over 30 days the stock has shed 10 percent, even as it added 3.7 percent across the last seven sessions — evidence that the selling pressure triggered by the trial failures has eased but not disappeared. A Relative Strength Index just under 40 stops short of signaling an oversold condition in the classical sense, yet it points to persistently weak price momentum.
The Question Behind the Failures
For institutional investors, the individual readouts are almost beside the point. What has drawn scrutiny is where the failed assets came from. Del-desiran originated in the pipeline of Avidity Biosciences, which Novartis acquired for USD 12 billion. Reuters explicitly tied the setback to that purchased program, turning a deal meant to fortify the pipeline into a case study in the hazards of expensive external acquisitions.
The concern is not that trials fail — that is inherent to drug development — but that Novartis may be leaning too heavily on billion-dollar M&A to drive growth without adequately pricing clinical risk. Reuters described a debate that reaches past any single study result and into the company's capital allocation. For a business that expands its pipeline largely through takeovers, that is no small matter.
Barclays had previously put the peak sales potential of the failed del-desiran at roughly USD 3.1 billion, assuming a 60 percent probability of success — a reminder of how much pipeline value was riding on that one candidate alone.
A Novartis spokesperson conceded that acquisitions carry inherent risk. At the same time, the company is pressing ahead on other fronts. It paid USD 125 million to biotech firm Sironax for global rights to a platform designed to shuttle active compounds across the blood-brain barrier, a building block for future treatments targeting neurological and rare brain diseases. Separately, the US subsidiary announced investments in data and AI capabilities covering 6,000 employees. Whether that reassures investors about the M&A approach is an open question.
Growth Targets Stay, Scrutiny Builds
Through the run of negative readouts, Novartis has left its medium-term guidance untouched: annual revenue growth of 5 to 6 percent for the 2025–2030 period. Portfolio pruning continues in parallel.
Still, the accumulation of setbacks is likely to pull investor attention toward the late-stage programs that remain. The central issue is not whether individual studies fail — they will — but whether Novartis subjects its multibillion-dollar purchases to more disciplined clinical-risk scrutiny going forward. That answer, more than any single trial result, is what will shape the share price in the months ahead.
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