Chief Executive Officer, President and Director at Vertex Pharmaceuticals
Thanks, Michael. Before we begin, as this will be Michael Partridge's last quarterly call with us, I'd like to take a moment to recognize Michael for his outstanding service and contributions to Vertex. For 25 years, he has been the face of Vertex with analysts and investors and with his calm and steady approach, Michael has led our IR team through countless milestones and many evolutions of the company. More recently, through the launch of all four of our marketed cystic fibrosis medicines and the emergence of our broad, mid- and late-stage pipeline, Michael has been an integral part of the Vertex leadership team, helping share our story with the world. Michael has shown a true passion for Vertex and the patients we serve.
We are grateful for his dedication, and I want to personally thank Michael for all that he's done for Vertex. On to the quarterly review. Vertex is off to an excellent start across the board with strong performance in the CF business, rapid advancement of the pipeline and continued operational excellence. Q1 CF product revenues grew 22% year-on-year to $2.1 billion, reflecting continued growth in the number of CF patients treated globally. And despite continued significant investment in internal and external innovation, our non-GAAP operating margins remained industry leading at 56%. We maintained a rapid pace of progress in research and across the clinical stage pipeline with a half a dozen programs now post the POC stage.
And we finished the quarter with a strong balance sheet and $8.2 billion in cash and investments. CF has been the exemplar of our R&D strategy. The last six to 12 months have made it clear. Our R&D strategy is proving itself beyond CF with the discovery and development of small molecules and cell and genetic therapies across a number of disease areas. This serial innovation enables the potential to transform, if not cure, multiple diseases and in so doing help more patients and drive long-term growth for the company. Fundamentally, the goal of our strategy grounded in causal human biology, validated targets and biomarkers that translate from bench to bedside and all the way through pivotal development is to increase the odds of success in drug discovery and development. With the data we've generated in CF, in sickle cell disease and beta thalassemia, and now in rapid succession with positive proof of concept in APOL1-mediated kidney disease, pain and type one diabetes, our clinical stage pipeline has never been broader in terms of the number of disease areas, more diverse in terms of modalities or more advanced.
The company is now at a new inflection point with continued growth in CF, the advancement of our broad clinical pipeline with six programs in mid- and late-stage development, representing multibillion dollar opportunities and the potential from the next wave of therapies approaching the clinic. In this next group of programs that have initiated IND-enabling studies is our mRNA program in CF, the cells plus device program in type one diabetes, the next wave of small molecule correctors in AATV and our in vivo gene editing program in DMD. A number of these programs are on track for IND filings later this year with clinical trials beginning thereafter. Our R&D strategy combined with our business model positions us well for continued innovation and sustained growth as we work to bring additional transformative medicines to more patients around the globe.
With this as context, I'll now review the R&D highlights for the quarter. Looking to our future in CF, we continue to strengthen our leadership for the long term. Our real-world experience with TRIKAFTA continues to accumulate, and as Stuart will discuss, raises the bar for any regimens in development. That said, if it is possible to outperform TRIKAFTA, we're determined to be the one to do so. Our next-in-class triple combination of VX-121/tezacaftor/561 is rapidly progressing through pivotal development. More than 180 clinical trial sites are open and enrolling patients in our Skyline Phase III program. We expect to complete enrollment by late 2022 or early 2023. As a reminder, VX-121/tezacaftor/561 has the potential for greater clinical benefit than TRIKAFTA and is a more convenient once-daily treatment that carries a lower royalty obligation for Vertex.
For the more than 5,000 patients who do not make any CFTR protein and cannot benefit, therefore, from a CFTR modulator, we are developing an mRNA therapy together with our partner, Moderna. IND-enabling studies for this program have been completed, and we remain on track to submit an IND in the second half of 2022 with clinical development starting thereafter. Turning to the pipeline beyond CF. Starting with CTX001, our gene editing approach designed to provide a potential functional cure for sickle cell disease and beta thalassemia. We plan to submit for U.S. and EU regulatory approvals for CTX001 for beta thalassemia and sickle cell disease by the end of 2022, and we expect this to be our next commercial launch. Enrollment in both Phase III studies is complete, and we have now dosed more than 75 patients across both programs. We look forward to sharing more clinical data on CTX001, including longer-term follow-up and more patients at medical forums this year.
Moving on to VX-147, our first-in-class small molecule inhibitor for people with APOL1-mediated kidney disease or AMKD, which has made rapid progress into pivotal development. In December, we reported unprecedented Phase II proof-of-concept results. In patients with FSGS, a particular kind of APOL1-mediated kidney disease, treatment with VX-147 led to a 47.6% reduction in proteinuria compared to baseline. VX-147 was generally well-tolerated. There were no SAEs related to VX-147, and all AEs were mild to moderate in severity. In late March, we initiated pivotal development of VX-147 following agreement with FDA and the design of the program, which included: one, a single adaptive Phase II/III study design in people with two APOL1 mutations, proteinuria and decreased renal function; two, evaluation of VX-147 in the broad AMKD population representing approximately 100,000 people in the U.S. and Europe with this disease; and three, the ability to conduct an interim analysis, which, if positive, could provide a pathway to accelerated approval in the U.S.
Transitioning now to our pain program. In late March, we announced that VX-548, a novel first-in-class, non-opioid NaV1.8 inhibitor achieved statistically significant and clinically meaningful relief in two Phase II studies of acute pain, meeting our high expectations. In the two studies, one following abdominoplasty and one following bunionectomy, VX-548 at the highest dose tested showed a rapid, sustained and consistent decrease in pain intensity compared to placebo on the primary endpoint of SPID48, a time-weighted sum of the pain intensity difference from time of first dose to 48 hours. In assessing the SPID48 score, it's important to note, higher scores indicate greater pain relief. VX-548 was superior to placebo with a statistically significant mean SPID48 of 37.8 in abdominoplasty, and 36.8 in bunionectomy.
In the reference arm of the study, standard of care opioid therapy showed a mean SPID48 difference from placebo of 12.5 and 14.7, respectively. From a safety and tolerability perspective, VX-548 was well-tolerated at all doses. There were no serious adverse events related to VX-548 and the majority of adverse events were mild or moderate. Given the high unmet need for an efficacious and well-tolerated, non-opioid pain medicine, we are working with urgency to advance VX-548. Our goal is to bring forward a novel class of pain treatment with the potential to provide effective pain relief without the addictive potential or adverse side effects of opioids. We plan to advance VX-548 into pivotal development for acute pain in the second half of 2022, pending discussions with regulators. I'll conclude with the type one diabetes program and VX-880, our stem cell-derived fully differentiated islet cell replacement therapy that could offer a functional cure for people living with type one diabetes. In the U.S. and Europe alone, type one diabetes affects more than 2.5 million people.
As we announced earlier this week, the VX-880 program has been placed on clinical hold in the U.S. by the FDA and we're working with urgency to understand more. At that time, we also shared the safety and efficacy data from the first three patients treated to date. To recap, the first patient was treated with half the target dose of cells, has achieved insulin independence at day 270, with a hemoglobin A1C level of 5.2%. The second patient also a half dose had positive results through day 150. The patient achieved robust increases in measures of pancreatic islet cell function and improved glucose control while simultaneously experiencing a 30% decrease in exogenous insulin use. Taken together, the results from patients one and patients two, both treated at half dose, demonstrate proof of concept for VX-880. The third patient who is the first to receive a full dose of VX-880 has reached the day 29 milestone. As of day 29, the patient showed encouraging early indications of efficacy, with increasing C-peptide levels and improving glycemic control. The first detailed assessment of pancreatic islet function and glycemic control for patients in the study occurs at the day 90 visit. Across the program, in the three patients dosed to date, there are no SAEs related to VX-880.
The majority of adverse events are mild to moderate, and the overall safety profile is consistent with the immunosuppressive regimen used in the study and the perioperative period. These are the data to date. Of course, all three patients will be continued to be followed per study protocol. We look forward to working constructively and expeditiously with the FDA to understand and address their questions so that we can resume the trial as soon as possible in the U.S. To close out on type one diabetes, a quick word on our cells plus device program.
We continue to make progress with our sales and device approach. In this program, instead of using immunosuppression to protect the cell from the immune system, the immunoprotective device is designed to serve that function. We remain on track for an IND filing for this program later this year. In summary, Vertex continues to deliver significant growth in CF, we're making rapid progress with programs in six disease areas in mid- and late-stage development, including five programs that are already in or entering pivotal development, with another wave of programs on track to enter the clinic starting later this year. We have a strong financial profile and balance sheet that enables continued investment to drive serial innovation.
With that, I'll turn it over to Stuart.