Reshma Kewalramani
Chief Executive Officer and President at Vertex Pharmaceuticals
Thanks, Charlie, and good evening all. Vertex continues to make strong progress towards our goal of reaching all CF patients eligible for our medicines. Based on the continued uptake of TRIKAFTA in the U.S. as well as in the international region, our Q2 CF product revenues grew 22% year-on-year to $2.2 billion. And based on this uptake as well as the new reimbursements recently secured, we are updating revenue guidance from $8.4 billion to $8.6 billion, to $8.6 billion to $8.8 billion.
We're also making rapid progress in advancing our R&D portfolio with programs in five disease areas now entering or progressing through late-stage clinical development, and the next wave of innovation getting ready to enter the clinic. Our expanding leadership in CF, coupled with the broad, deep and advanced research and clinical stage pipeline brings Vertex to this new inflection point highlighted last quarter.
This inflection point is rooted in our differentiated R&D strategy, which is designed to increase the odds of success in drug discovery and development. This strategy is working. First in CF and more recently, we have seen it deliver potentially transformative, if not curative therapies in multiple disease areas, including sickle cell disease, beta thalassemia, APOL1-mediated kidney disease, acute pain and type one diabetes, programs that are all now past the proof-of-concept stage.
Each of these programs individually represents a multibillion-dollar market opportunity. And taken together, they represent enormous potential for patients and for Vertex. In addition, we continue to use our strong balance sheet to pursue external innovation that complements or accelerates our internal efforts. The Viacyte acquisition, for example, has the potential to accelerate development of our type one diabetes programs.
The early stage assets from Catalyst and the Verve collaboration complement our internal efforts in sandbox diseases. With our strong revenue growth and rapidly advancing pipeline, we are continuing to invest in internal and external innovation, as you see us do today with the increase in opex guidance to $3 billion to $3.1 billion, and the multiple business development deals we've announced this quarter. Let me now turn to the pipeline and review some of our recent R&D progress. Starting with CF.
For patients who can benefit from CFTR modulators, TRIKAFTA has set a very high bar. But if it is possible to develop more effective medicines, we are determined to be the ones who do so. Our next-in-class triple combination, VX-121/tezacaftor/VX-561, is now in Phase III development enrolling patients 12 years and older, and we remain on track to complete enrollment by the end of this year or early next. With the progress in the SKYLINE one and SKYLINE two trials, we've also recently initiated pivotal development of VX-121/tez/VX-561 in patients six to 11 years old.
Lastly, for patients who do not make any CFTR protein and cannot benefit from a CFTR modulator, we're developing an mRNA therapy with our partners at Moderna. We are on track to file the IND for the mRNA program in the second half of this year. Moving to CTX001. Our most advanced pipeline program outside of CF is our exa-cel, or CTX001 gene editing program in severe sickle cell disease and beta thalassemia. In June, we presented data for more patients treated with exa-cel and with longer follow-up at the Annual Meeting of the European Hematology Association.
These data, which included 75 patients with up to 37 months of follow-up continue to demonstrate that exa-cel holds the potential to be a durable, onetime functional cure for these patients and the safety data continue to be consistent with myeloablative conditioning and autologous bone marrow transplant. In terms of next steps, we have recently concluded our discussions on the filing package with EMA and MHRA and have reached agreement on the filing package.
We remain on track to submit the MAAs in both sickle cell disease and beta thalassemia in the EU and the U.K. in Q4 of this year. We expect to wrap up our conversations with the FDA regarding the filing package, in particular, the number of patients and duration of follow-up, in the coming weeks, and we look forward to updating you after that. Turning now to inaxaplin, or VX-147 in APOL1-mediated kidney disease, or AMKD. Inaxaplin is a small molecule inhibitor of APOL1 that targets the underlying cause of AMKD.
Based on the unprecedented Phase II proof-of-concept results, which showed a 47.6% reduction in proteinuria, inaxaplin received Breakthrough Therapy designation in the U.S. and Priority Medicines, or PRIME designation in the EU. The pivotal trial is a single adaptive Phase II/III randomized, placebo-controlled trial, and the primary endpoint is the reduction in the rate of decline of kidney function in patients who have been treated for approximately two years. Importantly, the study is designed to have a preplanned interim analysis at 48 weeks of treatment.
If the interim analysis is positive, it will serve as the basis for us to seek accelerated approval in the U.S. We initiated the inaxaplin pivotal trial in late March, site activation, patient screening and enrollment are all ongoing. Moving to pain. And VX-548, a novel first-in-class NaV1.8 inhibitor. We have high expectations from this program because NaV1.8 is both a genetically and pharmacologically validated target across acute, neuropathic and musculoskeletal pain. And VX-548 demonstrated a very desirable benefit/risk ratio profile in Phase II.
Additionally, the VX-548 program represents a near-term commercial opportunity. To recap, earlier this year, we shared positive proof-of-concept results from VX-548, which demonstrated statistically significant and clinically meaningful relief of pain in two Phase II studies of acute pain, one in the post-bunionectomy setting and one in the post-abdominoplasty setting. Based on these results, the VX-548 has received Breakthrough Therapy designation, highlighting the significant need for highly efficacious and well-tolerated non-opioid pain medicines.
We are very pleased to have completed our end of Phase II meeting with the FDA and reach agreement on the VX-548 pivotal program in acute pain. The Phase III program will include two randomized placebo-controlled trials that will evaluate VX-548 post-bunionectomy and abdominoplasty. The exact same postsurgical acute pain settings we explored in Phase II. These trials are shortened duration, approximately two days of treatment followed by 14 days of safety follow-up. Both of these Phase III studies will also include an opioid treatment arm.
A third single-arm study will evaluate the safety and effectiveness of dosing with VX-548 for up to 14 days across multiple other types of moderate to severe acute pain. We remain on track to initiate the pivotal development program by the end of this year. In addition, we have completed our preclinical studies to support initiating a Phase II dose-ranging proof-of-concept study of VX-548 in neuropathic pain towards the end of this year. Turning now to type one diabetes. In June, our VX-880 clinical data were featured in an oral presentation at the ADA Scientific Sessions.
We've previously shared that we achieved proof-of-concept with the results from the first two patients who were treated in Part A with half the targeted dose. Both achieved glucose-responsive insulin secretion, improvements in hemoglobin A1C with concurrent reductions in or, as in the case of the first patient, elimination of exogenous insulin. The new data that we presented at ADA included glucose time and range measurements. Time and range is important because it gives much more granular and comprehensive data than hemoglobin A1C alone and is correlated with the risk of developing micro and macrovascular complications.
Patient one achieved a glucose timing range of 99.9% at day 270 versus 40.1% at baseline and remained insulin-independent. Patient two showed a glucose timing range of 51.9% at day 150 versus 35.9% at baseline with a 30% reduction in exogenous insulin. The trial, which has remained open in Canada and resumed enrollment in the United States last month, continues to screen and enroll patients in Part B.
To close, a word on the next wave of innovative therapies. These are programs in late preclinical development that are rapidly approaching the clinic. For the CFTR mRNA program, our cells and device program in type one diabetes and our next-generation AATD molecules, we expect to file INDs this year. Lastly, our gene editing program in DMD is in IND-enabling studies, and we plan to file the IND for this asset in 2023.
With that, I'll hand it over to Stuart for a commercial overview.