On November 2, 2023 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultrarare genetic diseases, reported its financial results for the quarter ended September 30, 2023 and provided its financial guidance for the year (Press release, Ultragenyx Pharmaceutical, NOV 2, 2023, View Source [SID1234636799]).
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"We’re in a strong financial position due to growing demand for our commercial products, completion of our recent offering, and our disciplined expense and portfolio management," said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. "We’ve also made significant progress on our key clinical programs and highlighted new, interim data from UX143 for osteogenesis imperfecta, GTX-102 for Angelman syndrome, and UX701 for Wilson Disease at our Analyst Day in October demonstrating promising therapeutic potential in these larger indications with further updates to come in 2024."
Third Quarter 2023 Selected Financial Data Tables and Financial Results
Revenues (dollars in thousands), (unaudited)
Three Months Ended September 30, Nine Months Ended September 30,
2023
2022
2023
2022
Crysvita
Product sales $ 19,200 $ 13,184 $ 57,318 $ 34,980
Royalty revenue 35,160 — 64,221 —
Non-cash royalty revenue 20,543 5,373 42,695 15,634
Revenue in profit-share territory — 51,348 69,705 148,121
Total Crysvita revenue 74,903 69,905 233,939 198,735
Dojolvi 16,553 13,274 47,347 39,200
Mepsevii 5,633 6,045 22,552 15,839
Evkeeza 963 — 1,540 —
Daiichi Sankyo — 1,479 1,479 6,207
Total revenues $ 98,052 $ 90,703 $ 306,857 $ 259,981
Total Revenues
Ultragenyx reported $98.1 million in total revenue for the third quarter 2023, which represents 8% growth compared to the third quarter 2022. Third quarter 2023 Crysvita product sales, primarily in Latin America, were $19.2 million, which represents 46% growth compared to the same period in 2022 and 14% growth over the second quarter 2023. Third quarter 2023 also includes Crysvita royalty and non-cash royalty revenue in North America of $50.2 million, which was impacted by a decrease in channel inventory related to Kyowa Kirin Co., Ltd.’s (KKC) change from Ultragenyx labeled product to KKC’s labeled product as part of the transition of North America commercialization responsibilities for Crysvita from Ultragenyx to KKC. This one-time change occurred in the third quarter 2023, and the Company expects Crysvita channel inventories to increase to more normal levels at the end of the year. Third quarter 2023 non-cash royalty revenue in Europe was $5.5 million.
Selected Financial Data (dollars in thousands, except per share amounts), (unaudited)
Three Months Ended September 30, Nine Months Ended September 30,
2023 2022 2023 2022
Total revenues $ 98,052 $ 90,703 $ 306,857 $ 259,981
Operating expense:
Cost of sales 10,987 8,631 33,158 23,001
Research and development 157,245 237,297 487,892 534,981
Selling, general and administrative 74,917 69,841 232,966 205,290
Total operating expense 243,149 315,769 754,016 763,272
Net loss $ (159,649 ) $ (245,106 ) $ (483,449 ) $ (555,588 )
Net loss per share, basic and diluted $ (2.23 ) $ (3.50 ) $ (6.81 ) $ (7.96 )
Operating Expenses
Total operating expenses for the third quarter of 2023 were $243.1 million, including non-cash stock-based compensation of $34.9 million. In 2023, annual operating expenses are expected to decrease compared to 2022, as the company manages headcount and increases operational leverage while executing on its high-value programs.
Net Loss
For the third quarter of 2023, Ultragenyx reported net loss of $159.6 million, or $2.23 per share basic and diluted, compared with a net loss for the third quarter of 2022 of $245.1 million, or $3.50 per share, basic and diluted.
Cash, Cash Equivalents and Marketable Debt Securities
Cash, cash equivalents, and marketable debt securities were $524.2 million as of September 30, 2023. This excludes net proceeds of $326.5 million from an underwritten public offering of common stock and pre-funded warrants that closed in October 2023.
2023 Financial Guidance
For the full year 2023, the company expects:
Total revenue in the range of $425 million to $450 million
Crysvita revenue in the range of $325 million to $340 million. This includes all regions where Ultragenyx will recognize revenue, including the royalties in Europe, which have been ongoing, and the royalties in North America, which began in April 2023.
Dojolvi revenue in the range of $65 million to $75 million
Net Cash Used in Operations to be around $425 million
Recent Updates and Clinical Milestones
UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Phase 2 demonstrated 67% reduction in annualized fracture rate and continuous improvements in bone mineral density
At the American Society of Bone and Mineral Research 2023 Annual Meeting (ASBMR), interim data from the Phase 2 portion of the Phase 2/3 Orbit study were presented that demonstrated treatment with setrusumab significantly reduced incidence of fractures in patients with OI with at least 6 months of follow-up and continued to demonstrate ongoing and meaningful improvements in lumbar spine bone mineral density (BMD). As of the cut-off date on August 4, 2023 and following at least six months of treatment with setrusumab, the annualized fracture rate across all 24 patients in the Phase 2 portion of the study was reduced by 67%. The median annualized fracture rate of 0.72 in the two years prior to treatment was reduced to 0.00 (n=24, p=0.042) during the mean treatment duration period of nine months. As of the data cut-off, there were no treatment-related serious adverse events (SAEs) observed in the study. Additional longer-term Phase 2 data are expected in 2024.
Patients are being dosed in the late-stage clinical trials, Orbit and Cosmic, which evaluate setrusumab in pediatric and young adult patients with OI. The Phase 3 portion of the Orbit study is targeting to enroll up to 195 patients at more than 50 sites across 12 countries. The Phase 3 Cosmic study is an active-controlled study evaluating the effect of setrusumab compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients aged 2 to <5 years. Cosmic is targeting to enroll approximately 65 patients at more than 20 global sites.
GTX-102 antisense oligonucleotide for Angelman syndrome: data from extension cohorts in Phase 1/2 study showed clinically meaningful improvements in multiple domains
In October 2023, interim data from the extension cohorts (Cohorts 4-7) in the ongoing Phase 1/2 for GTX-102 in Angelman syndrome were presented at an Analyst Day event. The data showed improvements across multiple domains compared to natural history data, where available, and clinical changes were associated with quantitative changes in EEG. Long-term data showed patients who stopped and restarted treatment reacquired previously gained developmental skills when they were re-dosed with the current regimen. As of the data cut-off, there have been no additional treatment-related SAEs, including lower extremity weakness, since November 2022.
Globally, sites are dosing patients in the expansion cohorts (Cohorts A-E), which will evaluate the same safety, pharmacokinetic, and efficacy measures as the extension cohorts. Data from at least 20 patients enrolled in the expansion cohorts, who have been on therapy for six months or more, are currently expected in the first half of 2024.
UX701 AAV gene therapy for Wilson Disease: Stage 1 of pivotal clinical study dosing patients; expect Stage 1 enrollment completion around the end of the year
In October 2023, interim data from the first dose cohort (5.0 x 10^12 GC/kg) in the ongoing Cyprus2+ study for UX701 in Wilson disease were presented at an Analyst Day event. The company announced four out of five patients in Cohort 1 had reductions in urinary copper and were tapering off of chelators and/or zinc therapy, including two of three earlier treated patients in the cohort that are now completely off standard of care therapy. As of the data cut-off, UX701 had been generally well-tolerated with no treatment-related SAEs.
Dosing in the second of three dose escalation cohorts in the pivotal study has been completed. The data safety monitoring board (DSMB) is scheduled to meet and will review the available safety data from Cohort 2 before making a recommendation on escalating to Cohort 3 of Stage 1 in this study. Stage 1 is currently on track to complete enrollment around the end of the year and these data are expected in the first half of 2024. During this stage, the safety and efficacy of UX701 will be evaluated and a dose will be selected for further evaluation in the pivotal, randomized, placebo-controlled stage of the study.
DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Dosing in Phase 3 study complete
In May 2023, Ultragenyx announced the last patient had been dosed in the Phase 3 study. The 48-week study has fully enrolled patients eight years of age and older, randomized 1:1 to DTX401 or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. Phase 3 data are expected in the first half of 2024.
DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study dosing patients
Ultragenyx is randomizing and dosing patients in the ongoing Phase 3 study. The pivotal, 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels. Enrollment is currently expected to be completed in the first half of 2024.
Conference Call and Webcast Information
Ultragenyx will host a conference call today, Thursday, November 2, 2023, at 2 p.m. PT/5 p.m. ET to discuss the third quarter 2023 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at View Source To participate in the live call, please register by clicking on the following link (View Source), and you will be provided with dial-in details. The replay of the call will be available for one year.