Guérir Quelquefois

There is a sentence carved into the tradition of the sanatorium at Saranac Lake. It is of uncertain origin and long associated with Edward Livingston Trudeau, and it has survived every advance in medicine since: Guérir quelquefois, soulager souvent, consoler toujours. To cure sometimes, to relieve often, to comfort always. Look at how it is built. The ambition falls as the frequency rises. The rarest achievement is named first and immediately qualified. It is a physician’s saying, written by someone who had watched a great many patients die.

The modern biotechnology pitch deck has turned the sequence upside down. “Cure” is now the most frequently used word in the sector and the least frequently delivered thing in it. This would be merely tiresome, the ordinary inflation of commercial speech, except that the word also bears weight. It holds up prices. It holds up financial models. In several notable cases it holds up an entire capitalization table, meaning the whole structure of who owns what in the company.

So it is worth asking a question that sounds like a schoolman’s diversion and is nothing of the kind: is a cure a prevention or a treatment?

The reflexive answer is that a cure is obviously a treatment, because one cures what already ails. Prevention acts before the disease, therapy acts on it, and a cure is simply therapy that finishes the job. That is clean enough. Now press on it.

Sofosbuvir cures hepatitis C. In curing it, it also prevents cirrhosis, liver cancer, and a place on the transplant list. Was that a treatment for a virus or the prevention of a cancer? It was both, in sequence, in the same patient, from the same pill. Which category you assign depends on where along the course of the disease you choose to stand, and that choice is made not by the molecule but by the person describing it.

This is not wordplay, because categories carry prices. Prevention is sold to the well: a huge population, a thin margin per person, purchasing by ministries and public programs, and permanent political scrutiny. Treatment is sold to the sick: a narrow population, an urgent buyer, and a willingness to pay that grows with fear. The same intervention, filed under different headings, produces different profit-and-loss statements. A firm that can plausibly describe its drug either way will describe it whichever way the room requires, and will not think of itself as lying.

There is a deeper structural embarrassment that the industry has never resolved and mostly avoids discussing in daylight. A chronic treatment is an annuity, a steady stream of payments. A cure is a liquidation, a one-time sale of everything.

Gilead’s hepatitis C franchise took in something like nineteen billion dollars worldwide in 2015, about twelve and a half billion of it in the United States. Three years later it was less than a fifth of that. The drugs had not failed. They had worked. The pool of existing patients was drained, and what remained was the far smaller flow of new cases. In April 2018 an analyst at Goldman Sachs put the matter in a report title that was received as a scandal: whether curing patients is a sustainable business model. It was merely arithmetic. A cure retires its own customers. Every honest model in the sector already knew this. The offense was writing it down.

This brings us to the one-time genetic therapies and their remarkable prices: Zolgensma, Hemgenix, Casgevy, Lyfgenia. The prices run into the millions and are defended explicitly against the lifetime cost of the alternative. Note what is doing the work in that defense. The word “cure” is not decoration there. It is the premise of the whole calculation of future savings. Remove it, by conceding that the effect may fade at year eight, that the vector (the delivery vehicle for the gene) may not persist, or that the patient may return to standard care, and the price becomes indefensible within an afternoon. That is why one increasingly finds outcomes-based warranties attached to these products, where the manufacturer agrees to refund the payer if the cure “uncures” itself. The warranty is an admission. Nobody insures against an outcome they believe is impossible.

Now the second half of the question, and the useful half: does the answer change depending on which representative of the company you ask?

It does, reliably, and the pattern is clear enough to use as a tool.

• The chief medical officer will not say “cure.” She will say “durable response,” “sustained remission,” or “potentially transformative,” and she will attach a median follow-up measured in months. She is speaking to the regulatory label, and the label is judged by people who require evidence over a time horizon nobody has yet observed.
• The chief financial officer will say “one-time, potentially curative.” That adverb is the entire prospectus. He is modeling a burst of existing patients over three to five years, followed by a thin steady state of new cases only. He is hoping nobody asks about year six before the fundraising closes.
• The chief executive, onstage in San Francisco in January, will say “cure,” unhedged, to applause.
• Market access, the team that negotiates with insurers and governments, will say whatever the payer needs to hear, which is a different sentence in every country.

Meanwhile the euphemism of the moment, “functional cure,” is spreading through hepatitis B and HIV. It is an adjective that quietly empties its noun. It means the disease is still there and has agreed to behave. As a clinical idea it is respectable and even hopeful. As an investment idea it is a trapdoor with a rug over it.

The practical instruction follows. Ask the question three times, of three people at the same company, and record not the answers but how much they differ. The difference is the finding.

A small difference is the ordinary drift of a word pressed into too many jobs at once, and it should be forgiven. A wide difference means one of two things. Either the company does not understand what it owns, or it understands perfectly and has assigned a different truth to each audience. The first is incompetence and the second is something worse, and the market has only one way of pricing either.

Trudeau’s sentence had one great virtue: it was honest about its own limits. Sometimes. The modern deck promises “always.” Pressed, it means “functionally.” Pressed again, it means “for as long as anyone has bothered to look.” The corruption of language comes before the corruption of thought, as a more famous essayist observed, and in this sector it comes before the corruption of the balance sheet by roughly one funding round.

So when the check is in front of you, hold the modern Guérir Quelquefois up against the old one. The old version graded itself honestly. It rose from the rarest thing to the most reliable and admitted at the outset that the first was uncommon. The version being sold to you runs the other way. It promises “always” from the stage and discloses its “sometimes” in the extension study, in a footnote, eighteen months after the raise. The entire equity value sits in the gap between those two documents.

Notice too that the drift is not only between firms. It is inside them, often inside one person on the same afternoon. The chief executive who says “cure” in the morning will say “durable response” to a regulator after lunch, and will mean no dishonesty by either, because the word has been quietly allowed to carry a different load in each room. That is exactly what makes it worthless as evidence and valuable as a signal. Price the variance, not the adjective. A company whose senior people converge, unprompted and across audiences, on the same careful sentence has decided what it owns. A company whose sentence changes with the room has not, and you are being invited to underwrite the difference.

The right question, then, was never whether the drug cures. It is what the word has been hired to do in the sentence, and who is paying its wages.