On May 4, 2021 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultra-rare genetic diseases, reported its financial results for the first quarter 2021 and reaffirmed its financial guidance for 2021 (Press release, Ultragenyx Pharmaceutical, MAY 4, 2021, View Source [SID1234579114]).

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"We continue to have strong Crysvita and Dojolvi launches and execute on our development priorities across our pipeline," said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. "In 2021, we will have ongoing pivotal trials for three gene therapies, one pivotal monoclonal antibody study for osteogenesis imperfecta, our first mRNA program for GSDIII, and an antisense oligonucleotide for Angelman with our partner GeneTx. These six clinical programs along with our commercial and early-stage programs make ours one of the most diversified pipelines in rare disease."

First Quarter 2021 Financials

In the first quarter 2021, Crysvita revenue in Ultragenyx territories1 increased 46% versus the first quarter 2020. This increase is driven by demand from pediatric and adult patients with X-linked hypophosphatemia (XLH) and patients with tumor induced osteomalacia (TIO), which became Crysvita’s second approved indication in the United States in June 2020.

Dojolvi revenue in the first quarter 2021 continued to build on the launch momentum after the U.S. Food and Drug Administration (FDA) approval in June 2020. As of the end of the first quarter 2021 the company has received approximately 230 completed start forms from approximately 115 unique prescribers. This has led to approximately 180 patients on reimbursed therapy as of the end of March 2021.

First quarter 2021 revenue included $42.8 million related to the technology transfer as part of the Daiichi Sankyo strategic manufacturing partnership around the HeLa PCL and HEK293 technologies. This revenue is expected to taper significantly through the end of this year as these activities come to a close.

Total operating expenses of $206.0 million in the first quarter 2021 increased 31% or $49.0 million versus the first quarter 2020, primarily driven by a $50.0 million expense for the upfront payment on the closing of the license and collaboration agreement with Mereo Biopharma. Excluding this upfront payment, total operating expenses for the year are expected to increase modestly as the company prepares for and enrolls six clinical programs, including four registrational studies.

Net cash used in operations for the quarter ended March 31, 2021 was $159.3 million, compared to net cash used of $95.2 million for the same period in 2020. Cash, cash equivalents, and marketable debt securities were $1.0 billion as of March 31, 2021.

2021 Financial Guidance

Crysvita Guidance in Ultragenyx Territories
The company reaffirms the 2021 guidance range for Crysvita that was provided at the beginning of the year. This range is $180 million to $190 million and includes the North American profit share region and the other regions where product sales are recognized.

Program Updates and Upcoming Milestones

Dojolvi for the treatment of Long-chain Fatty Acid Oxidation Disorders, or LC-FAOD

Health Canada approved Dojolvi for the treatment of adult and pediatric patients with LC-FAOD in February 2021 and the therapy was made commercially available to patients in Canada beginning in April 2021.
Recently published data2 under France’s nominative Authorization for Temporary Use program , or Authorisations Temporaires d’Utilisation (ATU), of 18 pediatric and adult patients with LC-FAOD showed that Dojolvi (triheptanoin) led to reductions in LC-FAOD manifestations and was well-tolerated, with median follow-up duration of 22 months (range 9-228 months). When comparing the year prior to treatment to the first year receiving Dojolvi, annual emergency hospital care visits decreased from a mean of 1.12 to 0.17, or an 85% reduction, and the mean number of emergency home care events decreased from 16.82 to 2.83, an 83% reduction. Similarly, the cumulative annual number of days of emergency home care were reduced from 286 in the year prior to receiving Dojolvi to 51 in the first year receiving Dojolvi, an 82% reduction. Further improvements in the cumulative annual number of days of emergency home care were seen during the second year receiving Dojolvi.
The efficacy and safety profile reported under the ATU is consistent with the results from prior reported data from the company-sponsored studies.
GTX-102 for the treatment of Angelman Syndrome, partnered with GeneTx

A pre-application meeting with a national regulatory agency in Europe was held in which the company reviewed the available efficacy and safety data as well as its proposal for dosing and administration of GTX-102. Based on our discussion, the authority agreed in principle on the expansion of the trial to Europe using the proposed modified study design, dosing and administration strategy, pending review of the application. The application to enroll the clinical study in this region was recently submitted.
In Canada, an amendment to the open clinical trial agreement was submitted and included the additional data and updated protocol and is pending review.
Discussions with the FDA are continuing and a request for a meeting has been granted and will take place in the second quarter 2021. The meeting will review additional clinical data requested by the FDA regarding the previously treated patients that confirm that the serious adverse event in the previously treated patients has fully reversed as well as an amended dosing plan for the previously treated patients.
The Phase 1/2 study is expected to resume in 2021, with clinical data on some patients still available before the end of 2021.
DTX401 for the treatment of Glycogen Storage Disease Type Ia, or GSDIa

Ultragenyx completed the Scientific Advice process with the European Medicines Agency (EMA) and an End-of-Phase 2 meeting with the FDA.
The Phase 3 study design has been submitted and endpoints are being finalized with regulators.
The Phase 3 study is expected to initiate early in the second half of 2021.
DTX301 for the treatment of Ornithine Transcarbamylase, or OTC, Deficiency

Late in the first quarter 2021, Ultragenyx met with the FDA in an End-of-Phase 2 meeting where the Phase 3 design and endpoints were finalized. The Phase 3 study will include a 64-week primary efficacy analysis period and enroll approximately 50 patients 12 years of age and older, randomized 1:1 to DTX301 (1.7 x 10^13 GC/kg dose) or placebo. The co-primary endpoints are the change in 24-hour plasma ammonia levels and the percentage of patients who achieve a response as measured by discontinuation or reduction in baseline disease management.
The final Phase 3 study design incorporates Scientific Advice feedback from the EMA.
The Phase 3 study is expected to initiate in the second half of 2021.
UX701 for the treatment of Wilson Disease

During the first quarter 2021, the Investigational New Drug (IND) application cleared FDA review. A seamless, single-protocol Phase 1/2/3 study is expected to begin early in the second half of 2021.
UX053 for the treatment of Glycogen Storage Disease Type III, or GSDIII

The IND application for UX053 for the treatment of GSDIII, the company’s most advanced mRNA program, was cleared by the FDA in March 2021. Enrollment in a Phase 1/2 study is expected to begin in the second half of 2021.
1: Ultragenyx territories include the collaboration revenue from the North American profit share territory and other regions where revenue from product sales are recognized by Ultragenyx. This excludes the European territory revenue, which is recognized as non-cash royalty revenue since the rights were sold to Royalty Pharma in December 2019.

2: View Source

Conference Call and Webcast Information

Ultragenyx will host a conference call today, Tuesday, May 4, 2021, at 2 p.m. PT/ 5 p.m. ET to discuss the first quarter 2021 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 by phone, dial (855) 797-6910 (USA) or (262) 912-6260 (international) and enter the passcode 6883837. The replay of the call will be available for one year.