Our persistence rates with our CFTR modulators are let me just reemphasize as high as I’ve ever seen for any chronic oral medication, but we do have patients who have discontinued over time. And so I think those patients who want to be on a CFTR modulator, but have to discontinue one of our previous generations may be interested in the vanzacaftor triple combination when a new treatment option is available. So I do think there is likely to be a significant interest from physicians and patients if the vanzacaftor triple combination delivers incremental benefits.
Reshma Kewalramani: Robyn, let me take the question about chronic pain next, and we’ll end with growth. We see pain as three distinct categories, acute pain, that’s what we’ve been talking about with VX-548 and this very near-term commercial opportunity, given we are well underway with our Phase 3 program, and it is only 48 hours of dosing. The second, we see is neuropathic pain. Obviously, that’s a version of chronic pain, but we distinguish that from musculoskeletal pain. For neuropathic pain, I see that as equally a Vertexian opportunity as is acute pain. There is a €“ there are discrete number of prescribers. It can be serviced with a specialty sales force. And we have already shown that this target NaV1.8 with our predecessor molecule, VX-150 is effective for neuropathic pain.
When LYRICA was a branded medicine, just to give you a sense of the market size, it was approximately a $5 billion market for LYRICA in this chronic neuropathic pain. And then there’s the third kind of pain, which is musculoskeletal pain. It turns out that we’ve already studied that as well with our predecessor molecule, and it’s effective in that kind of pain setting as well, which is actually quite unusual. There aren’t very many medicines that work in acute neuropathic and musculoskeletal pain. We are €“ I don’t see the musculoskeletal pain as a Vertex sales and marketing specialty opportunity, but we’re absolutely going to serve all patients and we would partner that, but our focus is on the two Vertexian opportunities right in front of us, acute pain, very near term, and the neuropathic pain that’s already in Phase 2 and the predecessor molecule with successful there.
With regard to growth, let me ask, Charlie to comment on the growth profile for the company.
Charlie Wagner: Yes. The question, so just a reminder on the guidance, we gave $9.55 to $9.7, 7% to 9% growth over 2022, and that’s after a 1.5 percentage point headwind from FX. Stating it differently, it’s a $700 million increment on €“ or 2022 revenue of $9 billion, so a significant increase in 2023. I think your question really was about where does growth come from? And so importantly, as has been mentioned, we’ve recently increased our estimate of epidemiology, several years ago, we used to say 75,000, then it was 83, now it’s 88. So the patient population is growing. Within that patient population, there are 20,000 patients or more who would benefit from a CFTR modulator who are not on medicine today. And we intend to bring as many of those as possible onto medicine, as we go with continued uptake across eligible patient groups in countries where we already have reimbursement or approvals, as we expand to younger age groups, and to a lesser extent, as we add additional new reimbursements.
And so we have high visibility into our guidance for 2023, and with those drivers, we see growth beyond 2023 as well. And of course, we have the emerging opportunity from the vanza triple and the mRNA therapy in coming years. So overall, we’re in great position for continued growth in 2023, and we see lots of opportunity for growth beyond 2023.
