Reshma Kewalramani
Chief Executive Officer and President at Vertex Pharmaceuticals
Thanks, Susie. Good evening all, and thank you for joining us on the call today. We've delivered another strong quarter and continued to drive execution across the company. By reaching more CF patients, third quarter global product revenue grew 6% versus the prior year period. And we are raising full-year 2023 CF product revenue guidance to approximately $9.85 billion. We are delivering on our marketed medicines in CF, while simultaneously preparing for commercial excellence in multiple areas, ahead of our potential near-term launches including exa-cel in both severe sickle cell disease and transfusion dependent beta thalassemia. VX-548 for acute pain and longer term in peripheral neuropathic pain and our Vanzacaftor triple combination therapy for cystic fibrosis. Most notably, we are tracking towards and exa-cel PDUFA date for sickle cell disease on December 8th of this year and for TDT on March 30th of next year with global regulatory reviews also underway in Europe and the UK. Phase 3 pivotal trial readouts in early 2024 from both our Vanzacaftor triple in CF and our VX-548 program in acute pain. A Phase 2 trial read out by year end 2023 from our VX-548 trial in diabetic peripheral neuropathy, and completion of enrollment in the Phase 2 portion of the VX-147 Phase 2/3 program in AMKD later this year.
With that overview, let me now turn to a pipeline update. Starting with cystic fibrosis. For our next in class Vanzacaftor triple combination therapy, we remain on track to complete all three Phase 3 studies SKYLINE 102 and 103 in patients ages 12 years and above and the RIDGELINE study in patients, ages six to 11 by the end of 2023 and share results from these three pivotal studies in early 2024. We have high expectations that the Vanzacaftor triple combination can deliver greater improvements in CFTR function than TRIKAFTA based upon the totality of evidence generated to date, including in-vitro from our HPE assays and in Phase 2 studies. The Vanzacaftor triple holds the potential for enhanced clinical benefit versus TRIKAFTA for patients and the convenience of once daily dosing. It also carries a substantially lower royalty burden.
In addition, we continue to make progress with another important program in our CF portfolio VX-522, our CFTR mRNA therapy in development with our partners at Moderna for the more than 5,000 CF patients who cannot benefit from CFTR modulators. We continue to expect to complete the single ascending dose portion and initiate the multiple ascending dose portion of this study by the end-of-the year.
Turning now to exa-cel, our CRISPR/Cas9 based gene editing program for sickle cell disease and transfusion dependent beta thalassemia. This program holds the potential to be a one-time functional cure for these debilitating and life shortening diseases. Exa-cel represents an enormous advancement for the estimated 32,000 people living with severe sickle cell disease and transfusion dependent beta thalassemia across the US and Europe. It is a large commercial opportunity. On the regulatory front, in the US, we were very pleased to have had the chance to discuss the exa-cel filing with members of the FDA Advisory Committee last week and to hear the very compelling stories from patients. The meeting represented a significant milestone for Vertex. And the first potential CRISPR/Cas9 based therapeutic. We look forward to our upcoming PDUFA dates and to the potential of bringing this precise durable gene editing therapy to patients.
Internationally, in both the UK and the EU, we are also well into the regulatory review process and expect regulatory decisions in these jurisdictions in the coming months. In addition, we recently submitted a marketing authorization application for exa-cel to the Saudi Food and Drug Authority or SFDA. I am pleased to share that exa-cel is the first medicine ever to receive breakthrough designation by the SFDA, reflecting both the high unmet need and the high enthusiasm for exa-cel in the Kingdom of Saudi Arabia. We look-forward to updating you in the coming months.
Moving on to the pain program, VX-548, our novel highly selective NaV1.8 inhibitor that holds the promise for effective pain relief without the side effects or addictive properties of opioids and therefore represents a significant commercial opportunity in both acute and neuropathic pain. The pace of the Phase 3 program in acute pain has been rapid, which we see as an indication of the high unmet need and strong patient and physician interest in an efficacious non-opioid acute pain therapy. We have completed the randomized controlled trial in abdominoplasty, the RCT and bunionectomy, and a single-ARM safety and efficacy study, remain on track to complete by the end of this year. As previously discussed, we will unblind analyze and share results on all three studies at the same time, and we expect to do so in early 2024. This comprehensive Phase 3 program has been designed to support a broad moderate-to-severe acute pain label and to enable prescribing and usage across multiple care settings.
We're also studying VX-548 in peripheral neuropathic pain or PNP, yet another area of high unmet need. Recall, we've previously demonstrated positive proof-of-concept with the predecessor molecule VX-150 in neuropathic pain. In diabetic peripheral neuropathy or DPN, I am pleased to share that we have completed our Phase 2 12-week dose-ranging proof-of-concept study. We anticipate sharing the results from this Phase 2 trial by the end of this year. As we await the DPN results, we are excited to initiate a second Phase 2 peripheral neuropathic pain study of VX-548 by the end-of-the year in lumbosacral radiculopathy or LSR. It's a type of neuropathic pain caused by the impairment of nerve roots in the area of the lumbar spine. Given the limited therapeutic options, the significant opportunity to serve a large number of patients and the promise that the NaV1.8 mechanism holds, we are excited to pursue the potential of VX-548 in each of these neuropathic pain types.
Next onto to type 1 diabetes, where we are evaluating stem-cell derived, fully differentiated, insulin-producing islet cells for people with type 1 diabetes. Our goal is to develop a potential one-time functional cure for the millions of people living with type 1 diabetes including the more than 2.5 million patients in North America and Europe alone. The VX-880 or naked cell program where we have already established proof-of-concept is foundational to the type 1 diabetes program as a whole. Here patients take standard immunosuppressants to protect the islet cells from the immune system. At EASD last month, we presented positive updated clinical data from all patients in Part A and B of the VX-880 study. With regard to study status, Part C of the study, which administers the full target dose with concurrent dosing is now fully enrolled.
Our second program, VX-264 or the cells plus device program encapsulates these same cells in a proprietary immunoprotective device and hence there is no requirement for immunosuppressants. We have begun enrollment in dosing in part a of the VX-264 for study. And finally, our third program still in the research stage is our hypoimmune cells in which we edit the same fully differentiated cells, so as to obviate the need for immunosuppressants.
Transitioning now to Inaxaplin or VX-147. The first potential medicine to target the underlying cause of APOL1 mediated kidney disease or AMKD. The Inaxaplin pivotal program for patients with AMKD is a single adaptive Phase 2/3 study with a pathway to accelerated approval in the US. The Phase 2b dose-ranging portion of the study continues to enroll and dose patients and we expect to complete enrollment by the end of this year. We now expect to select a dose and move to Phase 3 of the study in Q1 of 2024.
Now turning to alpha-1 antitrypsin deficiency or AATD. We have discontinued development of VX-864 for due to non-serious rash events in some patients in the Phase 2 program. Our next generation molecule VX-634 and VX-668, both have greater potency and better drug-like properties and are both in Phase 1 clinical trials. These trials continue to enroll and dose healthy volunteers. We look-forward to sharing more on AATD including next steps as we learn more in the coming months.
With that, I'll turn it over to Stuart.
