an october surprise

The Moderna-Merck melanoma cancer vaccine data arrived early 

Adam Feuerstein/STAT

As reporters, nothing juices your adrenaline, or spikes your frustration, more than a major embargo violation of the most highly anticipated data presentation at ESMO. All carefully laid plans went right out the window on the eve of the conference. We were NOT the guilty party. 

We were going to use the Friday lull before ESMO really gets hopping to preview the Phase 3 INTerpath-001 study, which evaluated Moderna and Merck’s mRNA cancer vaccine in patients with adjuvant melanoma.

But the data were leaked, so our story set for Saturday was published early. Let’s summarize:

The Moderna-Merck personalized mRNA cancer vaccine, intismeran, when added to Merck’s Keytruda, reduced the risk of disease recurrence in patients with melanoma by 42% compared to Keytruda with a placebo. Recurrence-free survival (RFS) measures how long patients live without melanoma returning.

The study also evaluated as a key secondary endpoint distant metastasis-free survival (DMFS), which is how long participants go without new lesions appearing in parts of the body other than where the cancer started. Here, intismeran-Keytruda reduced the risk of DMFS by 38% compared to Keytruda-placebo.

“This is the first phase 3 study to show that a treatment built from the unique fingerprint of a patient’s own tumour can reduce the risk of recurrence or death from cancer,” said Georgina Long of the Melanoma Institute Australia and The University of Sydney, Australia, in a statement provided by ESMO. Long was the lead investigator in the INTerpath-001 study and is set to present the data at the ESMO meeting on Saturday.

“For a patient, more time free of melanoma is a meaningful benefit in its own right,” she said. “Longer follow-up is needed to show an impact on melanoma-specific and overall survival, as well as whether the early benefit we are seeing across stages and subgroups holds, and which patients benefit most.”

Read our story for more information, context, and the debate arising from the data. We’ll also have more to say about intismeran and its potential impact for melanoma patients over the weekend.

Meantime, happy ESMO Embargo Breach Day, for all who celebrate. We aren’t.

Wall Street

The intismeran study was positive, so why did Moderna’s stock price plunge?

When Wall Street meets a medical meeting, strange things can happen. This is especially true when investors were already expecting very big things to happen.

The situation that Moderna (the stock, not the company) finds itself in at ESMO is what’s referred to by folks who sit in front of Bloomberg terminals all day as a “sell on the news event.” Stock prices often reflect future events and possibilities, and Moderna, which added $60 billion in market value just on the August intismeran press release, alone, had already priced in a lot of the therapy’s revenue upside.

If we’re being totally honest, Moderna’s tripled stock price and $90 billion market value overpriced the most optimistic intismeran business case. By how much is debatable, but to use more Wall Street jargon, the stock had gotten way ahead of itself.

So, that’s why Moderna’s stock price plunged 17% on Thursday when the intismeran data leaked. As this newsletter was put together, the stock was down another 1% Friday. That’s actually pretty good.

“This was a positive trial, and a very important outcome for patients and the field,” Jedd Wolchok, director of the Meyer Cancer Center at Weill Cornell Medicine and an immunotherapy pioneer, told STAT on Friday. “I don't quite understand what the reason for the disappointment was, but you know, I don't pretend to be smarter than a biotech analyst.”

This is not to say that the INTerpath-001 study leaves all questions answered. There will be debates. But investors on Wall Street and oncologists in Madrid are not always on the same wavelength.

“Taking a step back, the data were very much in line with expectations,” said Mizuho health care strategist Jared Holz, who graciously spoke to STAT Friday while touring colleges with his kid. “From the Wall Street perch, this was always going to be a tricky set-up for the stock given a parabolic move over the past month coupled with a $100 billion market value coming into ESMO.”

treatment optimization 

The trials we shouldn’t expect pharma to fund

At its recent conferences, ESMO has sought to highlight deescalation trials, studies that are meant to show whether giving less of a drug — smaller amounts, fewer doses, or a shorter duration — can maintain outcomes.

The idea behind the approach — also known as treatment optimization — is that it could lower the burden for patients and save money, while preserving the benefits of a medicine.

“By decreasing the amount of therapy you need to give to a patient, in fact you make accessible therapy because they are less expensive, the duration is less, you need less resources, less infrastructure,” Fabrice André, this year’s ESMO president, said at the meeting's opening press conference Friday.

The challenge in pursuing these studies is that drugmakers, which fund so many clinical trials, have little interest in generating evidence that could lead to people buying less of their products, and so typically won’t sponsor them, with limited exceptions.

But André, from France’s Institut Gustave Roussy, argued that it shouldn’t be up to the industry to back these studies. Instead, he said that academic researchers and public bodies need to take them on, and noted that ESMO and the European Union have started funding deescalation studies.

“We cannot forever ask everything to the pharmaceutical industry,” he said, adding that “this is not their role in the current landscape.”

Instead, André said, doctors need to say that “we are responsible for the way we deliver treatment, and we are responsible for optimizing treatment. It’s exactly why universities, research centers are here.”

At the opening briefing, André also highlighted guidance that ESMO released ahead of this year’s conference to encourage presenters to connect their data to the patients behind them.

“The starting point of this initiative was the observation that the way we communicate in scientific conferences is very dehumanized,” he said, noting that medical meetings don’t emphasize the fact that all the points in the charts that are displayed come from patients — many of whom die during these studies.

The ESMO Principles for Humanizing Scientific Reporting instead aim to better link study outcomes to the patient experience and real-world implications, even as the evidence from new research becomes increasingly complex. Recommendations include using accessible language in presentations and putting more of an emphasis on quality-of-life outcomes, in addition to typical endpoints like survival and progression.

“We want to reconnect scientific reporting … with the perceptions by the attendees that we are talking about human beings,” André said.