Novartis CEO Vas Narasimhan is doubling down on his $5 billion peak sales projection for Pluvicto, even as the company has given up on a label expansion in Europe.
Novartis withdrew its European Medicines Agency application for Pluvicto as a pre-chemotherapy treatment for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), the two parties announced Friday.
The withdrawal “reflected a different perspective on what is the appropriate comparator in this pre-taxane” setting, Narasimhan told reporters on a call Tuesday. While the PSMAfore trial tested Pluvicto against a change of androgen receptor pathway inhibitors, some doctors have argued that chemotherapy should be the standard of care for this patient population.
The European authorities requested another trial, but Novartis does not think it’s worthwhile, Narasimhan said.
Despite the regulatory setback, Narasimhan dismissed the impact of the withdrawal, noting that the company had not factored that European indication in its $5 billion peak sales estimate for Pluvicto because it had anticipated pushback from regulators.
Meanwhile, the PSMA-directed radioligand therapy (RLT) has made inroads since its pre-taxane approval from the FDA about a year ago. Pluvicto’s $642 million in first-quarter sales represented a 70% year-over-year increase at constant currencies, beating analysts’ consensus by 3%, according to ODDO BHF.
In the U.S. specifically, Pluvicto sales grew 76%, with more than 70% of the business coming from the pre-taxane use, Narasimhan said on a separate call with investors Tuesday.
“I think that all just gives us confidence now we’ve been able to make RLT standard that’s available now broadly in the communities that we serve, and also sets us up well for the future radioligand therapy portfolio over the coming years,” Narsimhan said.
The company expects the drug’s next inflection point will come from a potential FDA nod later this year in metastatic hormone-sensitive prostate cancer, which would add 75% to the number of patients who are eligible for Pluvicto.
Pluvicto might not go unchallenged in the PSMA field for too long. Astellas just signed on to accelerate the development of Vir Biotechnology’s PSMAxCD3 masked T-cell engager candidate, VIR-5500, with a phase 3 mCRPC trial planned for 2027.
What’s more, outside of PSMA, the broader prostate cancer field is seeing an influx of new candidates, including antibody-drug conjugates that are already in phase 3.
But Novartis remains committed to Pluvicto and its radioligand approach.
“Patients more and more want a very compelling profile with respect to quality of life, and that’s what Pluvicto delivers,” Narasimhan said on the media call. “Thus far, with T-cell engagers that we’ve looked at, we continue to see high rates of severe or strong reactions from side effect profiles that give us caution in terms of diving into that space.”
“We’ll continue to evaluate,” the Novartis CEO added. “We think, for now, Pluvcito has a very compelling profile that should allow us to get well beyond hopefully that $5 billion sales.”
Pluvicto is one of the key growth drivers for Novartis as it navigates the massive Entresto patent cliff. Until the heart failure med’s U.S. loss of exclusivity last summer, the drug was the company’s biggest-selling product.
As expected, sales of Entresto dropped sharply in the first quarter, falling 46% at constant currencies to $1.3 billion and missing analysts’ expectations by 7%, according to ODDO.
The Entresto freefall led to a 5% decrease in Novartis’ overall first-quarter sales, which came in at $13.1 billion. Core operating income plummeted by 14% driven by the sales decline and increased investments in R&D.