Ultragenyx (RARE) reports strong Phase 3 DTX301 gene therapy data in OTC deficiency

Rhea-AI Filing Summary

Ultragenyx Pharmaceutical Inc. reported positive Phase 3 Enh3ance results for DTX301, its investigational AAV8 gene therapy for ornithine transcarbamylase (OTC) deficiency. At Week 36, DTX301-treated patients showed an 18% reduction in 24-hour plasma ammonia AUC0-24 versus placebo, with ammonia levels generally maintained in the normal range.

Treated patients reduced ammonia scavenger medications by a mean 27% and increased protein intake by about 13%, while still keeping ammonia controlled. Patient-reported outcomes at Week 24 showed notably higher rates of symptom improvement with DTX301 compared to placebo. DTX301 was described as well tolerated, with most adverse events being mild to moderate hepatic reactions managed with steroids.

The trial continues to a second primary endpoint assessing reduction in treatment burden through 64 weeks, with additional data expected in the first half of 2027. Ultragenyx states that the program fits within its 2026 spending guidance and its goal of achieving profitability in 2027.

Positive

• Phase 3 efficacy: DTX301 achieved an 18% reduction in 24-hour plasma ammonia AUC0-24 versus placebo at Week 36, with ammonia generally maintained in the normal range.
• Quality-of-life signals: At Week 24, 71% of treated patients were rated much improved for OTC symptoms on the patient global impression scale, compared with 0% on placebo.
• Safety profile: DTX301 was described as well tolerated, with mostly mild to moderate hepatic events managed with steroids and fewer hyperammonemic crises and deaths than placebo.

Negative

• None.

Insights

Biotech and clinical-trials analyst

Strong Phase 3 efficacy and safety data support DTX301’s potential in OTC deficiency.

The Phase 3 Enh3ance study shows DTX301 achieved an 18% reduction in 24-hour plasma ammonia AUC0-24 versus placebo at Week 36 in OTC deficiency. Maintaining ammonia within the normal range despite lower scavenger use and higher protein intake suggests a robust biological effect in a difficult-to-manage disease.

Patient-reported outcomes reinforce this, with 71% of treated patients rated much improved on OTC symptoms at Week 24 versus none on placebo. Safety appears manageable, with mostly mild to moderate hepatic events, one treatment-related acute hepatitis that resolved with steroids, and fewer hyperammonemic crises and deaths than placebo.

The study is ongoing to a second primary endpoint on treatment burden through 64 weeks, with data expected in the first half of 2027. Ultragenyx notes that development plans for DTX301 are reflected in its 2026 spend guidance and target of profitability in 2027, but regulatory outcomes and longer-term data will be critical for eventual commercial impact.

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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): March 12, 2026

Ultragenyx Pharmaceutical Inc.

(Exact name of Registrant as Specified in Its Charter)

Delaware			001-36276	27-2546083
(State or Other Jurisdiction of Incorporation)			(Commission File Number)	(IRS Employer Identification No.)
60 Leveroni Court
Novato, California				94949
(Address of Principal Executive Offices)				(Zip Code)

Registrant’s Telephone Number, Including Area Code: 415 483-8800

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock, $0.001 par value		RARE		Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 8.01 Other Events.

On March 12, 2026, Ultragenyx Pharmaceutical Inc. (the “Company”) issued a press release announcing positive results from its Phase 3 Enh3ance study of DTX301, an investigational AAV8 gene therapy for the treatment of ornithine transcarbamylase (“OTC”) deficiency. At Week 36 in the randomized, double-blind placebo-controlled period of the trial, DTX301-treated patients (n=18) demonstrated a statistically significant and clinically meaningful 18% (p=0.018) reduction in 24-hour plasma ammonia (“AUC0-24”) compared to placebo (n=19) and maintained average ammonia AUC0-24 in the normal range through Week 36. Eight of nine patients with abnormal ammonia AUC0-24 at baseline despite optimal current drug treatment and diet restriction reached normal ammonia levels rapidly, which were generally maintained during this treatment period.

Baseline 24-hour ammonia AUC levels were normal in 50% of DTX301-treated patients and 68% of placebo patients, who were all on current care of scavenger medications and strict dietary control of protein intake. Patients treated with DTX301 (n=18) experienced reductions in 24-hour ammonia rapidly by Week 6 and were decreased by 18% (p=0.018) compared to placebo (n=19) at Week 36. Ammonia was generally maintained in normal range in treated patients despite their mean 27% reduction in ammonia scavenger medications at Week 36 (n=18) and an approximately 13% increase in protein intake relative to no change in placebo (n=19).

Assessed at Week 24, patient global impression scale (“PGIC”) for OTC symptoms (total n=15 reporting) overall showed 71% of treated patients were much improved (equivalent to +3) versus 0% of placebo. For Week 24, PGIC evaluations of OTC deficiency symptoms and OTC impact on daily living (total n=30 reporting), both showed 64% were either much improved (43%) or moderately improved (21%) and on placebo only 19% were moderately improved (none were much improved).

DTX301 was well tolerated with an acceptable safety profile, consistent with prior Phase 1/2 safety data. The most common treatment-emergent adverse events were mild to moderate transient hepatic reactions managed with steroids. One serious adverse event (“SAE”) of acute hepatitis was assessed as treatment-related and resolved with steroids. No SAEs or AEs related to thrombotic microangiopathy, dorsal root ganglion toxicity, malignancies, or other complex immune reactions. Hyperammonemic crises requiring hospitalization occurred five times in the placebo group with one death, and only one such event in the treated group and no deaths. Two patients in the placebo arm discontinued, including one death due to hyperammonemia crisis and one patient who became AAV8 antibody positive prior to crossover. One patient in the DTX301 arm discontinued after Week 36 for non-clinical reasons.

As planned, the study is continuing to its second primary endpoint which evaluates reduction in treatment burden, including use of ammonia scavengers and dietary management, across both the treatment and placebo-crossover groups following treatment with DTX301 through 64 weeks of follow-up. Data are expected in the first half of 2027. The conduct of the program is reflected in the Company’s February 2026 guidance on 2026 spend and will be managed within the company goals of 2027 profitability.

Cautionary Note Regarding Forward-Looking Statements

This Current Report on Form 8‑K contains forward‑looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of words such as, but not limited to, “anticipates,” “expects,” “plans,” “continues,” “will,” “may,” “potential,” or other similar terms or expressions that concern the Company’s expectations, plans, objectives, and intentions.

Forward‑looking statements include, without limitation, statements regarding the related to the development, timing and progress of DTX301, the timing, scope and outcome of future data results from the Phase 3 study of DTX301, including data expected in the first half of 2027, future regulatory interactions related to DTX301, the safety and tolerability profile of DTX301, the potential clinical benefit of DTX301 for patients with OTC deficiency, business plans and objectives for DTX301 and the management of development activities within the Company’s previously issued guidance on 2026 spend and its goal of achieving profitability in 2027.

These forward‑looking statements are based on current expectations and assumptions that are subject to substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward‑looking statements. Such risks and uncertainties include, among others: the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, the risk that interim or topline clinical results may not be predictive of final study results or longer‑term outcomes, the ability of the Company to successfully develop DTX301, complexities related to the development of gene therapy product candidates such as DTX301, the Company’s ability to achieve its projected development goals

in its expected timeframes, risks related to adverse side effects, risks related to reliance on third party partners to conduct certain activities on the Company’s behalf, smaller than anticipated market opportunities for the Company’s products and product candidates, manufacturing and supply risks, the ability of the Company and its third party manufacturers to comply with regulatory requirements, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and drug candidates.

The Company undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 18, 2026, and its subsequent periodic reports filed with the SEC.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

			Ultragenyx Pharmaceutical Inc.
Date:	March 12, 2026	By:	/s/ Howard Horn
			Howard Horn Executive Vice President, Chief Financial Officer, Corporate Strategy

FAQ

What did Ultragenyx (RARE) report about its DTX301 Phase 3 Enh3ance study?

Ultragenyx reported positive Phase 3 Enh3ance results for DTX301 in ornithine transcarbamylase deficiency. DTX301-treated patients showed significant ammonia reductions versus placebo and generally maintained normal ammonia levels, supporting the therapy’s potential clinical benefit in this rare metabolic disorder.

How much did DTX301 reduce ammonia levels in Ultragenyx’s Phase 3 trial?

DTX301-treated patients achieved an 18% reduction in 24-hour plasma ammonia AUC0-24 compared with placebo at Week 36. Ammonia levels were generally maintained within the normal range, even as treated patients reduced scavenger medications and increased dietary protein intake during the study period.

What patient-reported outcomes were seen with DTX301 in Ultragenyx’s Enh3ance study?

At Week 24, 71% of DTX301-treated patients were rated much improved for OTC symptoms on the patient global impression scale, versus 0% on placebo. Broader evaluations showed 64% of treated patients were much or moderately improved, compared with 19% moderately improved on placebo.

How was the safety profile of DTX301 described in Ultragenyx’s Phase 3 data?

DTX301 was described as well tolerated with an acceptable safety profile, consistent with prior Phase 1/2 data. Most adverse events were mild to moderate transient hepatic reactions managed with steroids. One treatment-related acute hepatitis resolved, and fewer hyperammonemic crises and deaths occurred versus placebo.

What are the next steps for Ultragenyx’s DTX301 program after these Phase 3 results?

The Enh3ance study is continuing to a second primary endpoint focused on reducing treatment burden, including ammonia scavenger use and diet management, through 64 weeks of follow-up. Ultragenyx expects data from this phase in the first half of 2027, guiding future regulatory interactions.

How does the DTX301 program align with Ultragenyx’s financial goals?

Ultragenyx stated that the conduct of the DTX301 program is reflected in its February 2026 guidance on 2026 spending. It also indicated these activities will be managed within its broader corporate objective of achieving profitability in 2027, integrating development plans with financial targets.

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