Chief Executive Officer and President at Vertex Pharmaceuticals
Thanks, Susie. We're delighted to have you on Board. Good evening all, and thank you for joining us on the call today. Vertex continues to execute exceptionally well and make significant progress towards our goals of: one, reaching all patients with cystic fibrosis resulting in strong sustainable growth; two, advancing our diverse mid- and late-stage clinical pipeline to develop transformative medicines in multiple disease areas; three, preparing for our next commercial launches; and four, progressing the next wave of innovation towards the clinic. In the third quarter, global CF product revenues increased 18% year-on-year to $2.3 billion as more patients initiated treatment with our CFTR modulators. Based on the strong performance, we are raising full year 2022 product revenue guidance from $8.6 billion to $8.8 billion to $8.8 billion to $8.9 billion.
Despite the growing numbers of CF patients on CFTR modulators, we still have many more patients to reach. And as you will hear from Stuart, we are working with focus and urgency to reach all patients around the globe who may benefit from our therapies. As previously discussed, we are at an important inflection point for the company. Each of our clinical stage programs, sickle cell disease and beta-thalassemia, acute pain, AMKD, type one diabetes and AATD is a first-in-class or best-in-class approach that holds the promise to transform the disease and each represents a multibillion dollar opportunity. With a uniquely strong and durable CF franchise, a broad and deep R&D pipeline with multiple potentially near-term commercial opportunities, a strong balance sheet and the capacity to invest in both internal and external innovation and deeply talented people, Vertex is well positioned to deliver for patients and shareholders for years to come.
With that overview, I'll turn to the details of recent R&D progress, starting with CF. TRIKAFTA sets a very high bar in terms of safety and efficacy in the registrational trials as well as in real world and long-term studies. That said, if it is possible to develop even more effective medicines for CF patients, we are determined to be the company that does so. Our next-in-class triple combination, VX-121/tezacaftor/VX-561, holds that potential. The triple now referred to as vanzacaftor, tezacaftor, deutivacaftor or the vanzacaftor triple is progressing rapidly through Phase III development with our studies in patients ages 12 and older, now projected to complete enrollment this year. As a reminder, this combination demonstrated greater activity in our human bronchial epithelial assay versus TRIKAFTA and greater clinical benefit in phase two than we have seen with any of our prior medicines. Additionally, it offers the convenience of once-daily dosing and royalties in the low single digits versus low double digits for TRIKAFTA.
For the 5,000 patients who do not make any CFTR protein, we're working on an mRNA therapy with our partners at Moderna. We have completed IND-enabling studies, and we remain on track to submit an IND for this program this quarter with clinical trials starting thereafter, and we're not done. Our work continues to identify even better potential therapies that could bring more patients with CF to carrier levels of sweat chloride. Turning to exa-cel, previously known as CTX001, our gene editing program for severe sickle cell disease and transfusion-dependent beta-thalassemia, or TDT. This is our most advanced program outside CF, and we expect exa-cel to be our next commercial launch. In June, we presented data from 75 patients with up to 37 months of follow-up from our pivotal trials of exa-cel. The data demonstrated exa-cel's potential to provide a onetime functional cure for these patients. Last month, we announced that in addition to having granted virtually all available U.S. regulatory designations, the FDA has now also granted exa-cel a rolling review. We plan to begin our BLA submissions for both sickle cell disease and beta-thalassemia in the U.S. next month, and complete the submissions by the end of the first quarter of 2023.
In Europe, we previously shared that we reached agreement on the filing package with the EMEA and MHRA in the EU and U.K., respectively. We remain on track to submit these MAAs by the end of this year. Our teams are intensely focused on preparing these multiple complex submissions with three separate regulatory agencies in order to bring exa-cel to patients as quickly as possible. Given that priority, we will not be sharing new clinical data at ASH, but instead, look forward to sharing updated clinical data in the first half of 2023. Exa-cel holds the promise for a onetime curative therapy for thousands of patients with severe sickle cell disease and transfusion-dependent beta-thalassemia. This therapy, potentially the first CRISPR-based gene editing treatment to be commercialized for patients with a genetic disease also represents a near-term and significant market opportunity.
Turning to VX-548 and our pain program. VX-548 is a novel selective NaV1.8 inhibitor that offers the potential of highly effective pain relief without the side effects or addictive potential of opioids. NaV1.8 is both a genetically and pharmacologically validated target. Recall that VX-150, an earlier-generation NaV1.8 inhibitor, demonstrated positive proof of concept in acute, neuropathic and musculoskeletal pain. VX-548 has been studied in two phase two placebo-controlled acute pain studies and showed statistically significant and clinically meaningful pain relief compared to placebo and was generally well tolerated. The study also included an opioid reference arm to support the evaluation of VX-548. With regard to the regulatory status, VX-548 has been granted fast track and breakthrough therapy designation in the U.S.
We reached agreement with the FDA on the design of the phase three program in support of a broad label in moderate to severe acute pain and recently initiated the pivotal studies. The phase three development plan for VX-548 in acute pain consists of two randomized controlled trials. The design of the RCTs in the pivotal program is very similar to our phase two completed studies, same pain states, post bunionectomy and post abdominoplasty. Same treatment duration, 48 hours and the same primary endpoint, the sum of pain intensity difference, or SPID, over 48 hours of VX-548 compared to placebo. A third single-arm study rounds out the phase three program. This study will enroll patients with multiple other types of moderate to severe acute pain with a treatment period of up to 14 days.
Given our experience in executing these types of trials efficiently, the short treatment duration and the high unmet need for effective pain relief without the significant side effects or addictive potential of opioids, we view VX-548 as a near-term and significant market opportunity. We also plan to study VX-548 in neuropathic pain and remain on track to initiate a phase two dose-ranging proof-of-concept study in patients with painful diabetic neuropathy towards the end of this year. Moving to inaxaplin or VX-147, the first potential medicine to treat the underlying cause of APOL1-mediated kidney disease, or AMKD. Inaxiplin has breakthrough therapy designation in the U.S. and both prime and orphan drug designation in Europe. Inaxaplin is being studied in a single adaptive, randomized, double-blind, placebo-controlled, phase two-three pivotal trial and the primary endpoint is a reduction in the rate of decline of kidney function in patients treated with inaxaplin on top of standard of care compared to standard of care for approximately two years. Importantly, the trial is a preplanned interim analysis at 48 weeks of treatment, which if positive, could serve as the basis for accelerated approval in the U.S. This study is underway in enrolling patients.
We now have more than 50 sites open for enrollment in the U.S. and internationally with a goal to open more than 150 sites in total. We look forward to updating you on the enrollment and study progress as the trial advances. Next, moving on to type one diabetes. We have been advancing three programs in our portfolio. First, VX-880, our stem cell-derived, fully differentiated insulin-producing islet cell replacement therapy, which is a mid-stage clinical development. In this program, we use standard immunosuppressive therapy to protect the cells from the immune system. These same cells are the foundation for our other two programs in type one diabetes. Next, the cells plus device program, which encapsulates these fully differentiated islet cells in a proprietary device that shields the cells from the body's immune system and does not require immunosuppressants.
We remain on track to file the IND for this program by the end of this year. Lastly, in our hypoimmune cells program, which is in preclinical development, we are editing the same fully differentiated insulin-producing islet cells to cloak them from the immune system, obviating the need for immunosuppressants. Earlier this year, we achieved proof of concept for VX-880 in type one diabetes with the first two patients dosed at half dose in Part A of the study. Part B of the study, which uses the full target dose is underway and enrolling patients. The type one diabetes program holds enormous potential. There are more than 2.5 million patients in the U.S. and EU alone with type one diabetes who may benefit from a treatment with the potential to provide glucose control without the fear of hypoglycemia or the need for insulin. We look forward to sharing additional data from more patients and longer duration of follow-up at the appropriate time.
A last word on our type one diabetes program. Having recently closed the acquisition of Viacyte, I want to extend a warm welcome to our Viacyte colleagues. Let me close with our Alpha-1 antitrypsin deficiency, or AATD program. Earlier this month, we announced that the IND for VX-634, the first in a series of next wave AAT correctors has cleared, and VX-634 has entered first-in-human clinical trials. We also announced that a 48-week Phase II study of VX-864, our first-generation AAT corrector will soon initiate. This study will assess the impact of longer-term treatment on polymer clearance from the liver as well as on serum levels of functional AAT.
With those R&D highlights, I'll hand it over to Stuart for a review of our commercial progress.