BioMarin Provides Update on Phase 3 Trial for BMN 401 in Children Aged 1-12 With ENPP1 Deficiency

Rhea-AI Summary

BioMarin (Nasdaq:BMRN) reported top-line Phase 3 ENERGY 3 results for BMN 401 in children aged 1-12 with ENPP1 deficiency. One co-primary endpoint was met, with statistically significant increases in plasma PPi through week 52 versus control, but no corresponding improvement in RGI-C or secondary clinical endpoints.

BMN 401 was generally well-tolerated with no new safety signals, and BioMarin is evaluating next steps. Detailed data will be shared at a future medical meeting.

Positive

• Statistically significant increases in plasma PPi through week 52 versus control
• BMN 401 generally well-tolerated with no new safety signals reported

Negative

• No improvement in Radiographic Global Impression of Change (RGI-C) co-primary endpoint
• No positive trends in secondary endpoints, including Rickets Severity Score and growth Z-scores
• Clinical benefit of BMN 401 in ENPP1 deficiency remains uncertain pending further evaluation

News Market Reaction – BMRN

-4.13%

-4.13% News Effect

On the day this news was published, BMRN declined 4.13%, reflecting a moderate negative market reaction.

Data tracked by StockTitan Argus on the day of publication.

Market Context

This announcement details pivotal Phase 3 ENERGY 3 data for BMN 401 in ENPP1 deficiency, showing sta...

Analysis

This announcement details pivotal Phase 3 ENERGY 3 data for BMN 401 in ENPP1 deficiency, showing statistically significant plasma PPi increases but no improvement in RGI-C, rickets severity or growth Z-scores. The company is evaluating next steps, and prior clinical updates on PALYNZIQ and ROCTAVIAN highlight both successful label expansion efforts and long-term gene therapy data. Investors may track future disclosures on BMN 401 strategy and how resources shift across BioMarin’s rare-disease pipeline.

Key Figures

Phase: Phase 3 Age range: 1–12 years Co-primary endpoints met: 1 of 2 +3 more

6 metrics

Phase Phase 3 ENERGY 3 trial for BMN 401

Age range 1–12 years Children with ENPP1 deficiency in ENERGY 3

Co-primary endpoints met 1 of 2 Plasma PPi improved; RGI-C showed no improvement

Biomarker duration 52 weeks Statistically significant plasma PPi increase through week 52 vs control

RGI-C outcome No improvement Radiographic Global Impression of Change scores showed no benefit

Secondary endpoints No positive trends RSS and growth Z-score (height/length and weight)

Previous Clinical trial Reports

4 past events · Latest: Oct 29 (Positive)

Same Type Pattern 4 events

Date	Event	Sentiment	24h Move	Catalyst
Oct 29	Label expansion review	Positive	-3.0%	FDA accepted PALYNZIQ sBLA for Priority Review for adolescents with PKU.
Sep 06	Pivotal trial data	Positive	-2.4%	Positive Phase 3 PEGASUS results showed strong Phe reductions in adolescents.
Jun 24	Long-term efficacy data	Positive	+1.1%	Five-year Phase 3 ROCTAVIAN data showed sustained efficacy and safety in hemophilia A.
Jun 07	Long-term safety update	Positive	-0.2%	Four-year ROCTAVIAN Phase 3 data confirmed long-term safety and bleed control.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Pattern Detected

Clinical trial and regulatory updates for BioMarin have often been positive on fundamentals but followed by flat-to-negative price moves, showing frequent divergence between news tone and short-term trading.

Recent Company History

Over the past year, BioMarin’s clinical news has focused on expanding indications and reinforcing long-term efficacy. PALYNZIQ updates for adolescents with PKU, including a Priority Review sBLA and positive Phase 3 PEGASUS data, highlighted strong reductions in blood phenylalanine and a Feb. 28, 2026 PDUFA date. ROCTAVIAN Phase 3 data at ISTH 2024 and 2025 underscored durable bleed control and sustained Factor VIII activity. Against this backdrop, the BMN 401 ENERGY 3 results add a mixed outcome: biomarker improvement without corresponding clinical benefit in ENPP1 deficiency.

Key Terms

phase 3, enpp1 deficiency, plasma inorganic pyrophosphate (ppi), radiographic global impression of change (rgi-c), +4 more

8 terms

phase 3 medical

"results from the pivotal Phase 3 ENERGY 3 trial evaluating BMN 401"

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

enpp1 deficiency medical

"children aged 1-12 with ENPP1 deficiency, a rare, serious and progressive genetic condition"

ENPP1 deficiency is a rare genetic disorder in which the body lacks enough of an enzyme (ENPP1) that normally helps control mineral balance, so calcium and phosphate can build up in soft tissues and blood vessels and impair bone and organ function. For investors, it signals an area of high unmet medical need where new drugs or gene therapies could command significant clinical and commercial attention, but also carry development, regulatory and pricing risks similar to other orphan-disease programs.

plasma inorganic pyrophosphate (ppi) medical

"statistically significant increases in plasma inorganic pyrophosphate (PPi) concentration"

Plasma inorganic pyrophosphate (PPi) is a naturally occurring small molecule in the blood that acts like an “anti-scale” agent, helping prevent unwanted calcium deposits in tissues and blood vessels. For investors, PPi is important because its level can serve as a biomarker of diseases involving abnormal calcification and a target for drugs; changes in PPi can affect clinical trial results, regulatory decisions, and the commercial prospects of therapies aimed at reversing or preventing tissue hardening.

radiographic global impression of change (rgi-c) medical

"no improvement was observed in Radiographic Global Impression of Change (RGI-C) scores"

Radiographic Global Impression of Change (RGI-C) is a clinician or expert reader’s overall judgment, based on medical images, of whether a patient’s physical condition has meaningfully improved, stayed the same, or worsened compared with baseline. For investors, RGI-C provides a simple, visual measure of a treatment’s structural impact (like comparing before-and-after photos), which can influence clinical value, regulatory decisions and commercial prospects when image-based outcomes matter.

rickets severity score (rss) medical

"no positive trends were observed across secondary endpoints, including Rickets Severity Score (RSS)"

Rickets Severity Score (RSS) is a numeric scale clinicians use to rate how badly a child’s bones are affected by rickets, a disease caused by poor mineralization often from vitamin D or calcium deficiency. Think of it like a damage meter for bone X‑rays: higher numbers mean more severe changes. For investors, RSS is important because it often serves as a clinical trial endpoint or regulator-observed outcome that helps judge whether a treatment is effective and therefore how a drug or therapy might perform commercially.

growth z-score medical

"secondary endpoints, including Rickets Severity Score (RSS) and growth Z-score (height/body length and weight)"

A growth z-score is a standardized measure that shows how far a company’s growth rate (for example, revenue or earnings growth) sits above or below a typical level, expressed in units of standard deviation. For investors it converts raw growth numbers into a common scale so you can quickly spot unusually fast or slow growth compared with peers or the company’s own history — like using a thermometer to see whether growth is unusually hot or cold and to gauge potential risk of reversing.

co-primary endpoints medical

"ENERGY 3 study met 1 of 2 co-primary endpoints in children with ENPP1 deficiency"

Co-primary endpoints are two or more key outcomes that a clinical study must meet simultaneously to be considered successful, like needing both improved symptoms and a marker of disease reduction. For investors, they matter because meeting multiple agreed goals strengthens the evidence that a treatment works and can influence regulatory approval, market access and commercial potential—similar to a product needing to pass both safety and performance checks before launch.

statistically significant technical

"Treatment with BMN 401 led to statistically significant increases in plasma inorganic pyrophosphate"

"Statistically significant" means that a result or difference observed in data is unlikely to have occurred by chance alone, suggesting there is a real underlying effect. For investors, it indicates that the findings or patterns they see are likely meaningful and not just random noise, helping them make more informed decisions based on reliable information. Think of it as a pattern that is strong enough to stand out clearly from background randomness.

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ENERGY 3 study met 1 of 2 co-primary endpoints in children with ENPP1 deficiency

Treatment with BMN 401 led to statistically significant increases in plasma inorganic pyrophosphate (PPi) concentration, one of the study's co-primary endpoints; however, no improvement was observed in Radiographic Global Impression of Change (RGI-C) scores, the study's other co-primary endpoint and an important clinical measure of change in rickets severity

Company is evaluating data to determine next steps

SAN RAFAEL, Calif., May 18, 2026 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced results from the pivotal Phase 3 ENERGY 3 trial evaluating BMN 401 in children aged 1-12 with ENPP1 deficiency, a rare, serious and progressive genetic condition. Deficiency in ENPP1 function results in a decrease in plasma inorganic pyrophosphate (PPi) that can lead to progressive damage to blood vessels, soft tissues and bones.

The study met one co-primary endpoint, showing treatment with BMN 401 resulted in statistically significant increases in plasma PPi through week 52 compared to the conventional therapy control arm in children with ENPP1 deficiency. However, the study did not meet its other co-primary endpoint as there was no corresponding improvement in Radiographic Global Impression of Change (RGI-C) scores, an important measure of treatment impact in children with rickets. Additionally, no positive trends were observed across secondary endpoints, including Rickets Severity Score (RSS) and growth Z-score (height/body length and weight). BMN 401 was generally well-tolerated with no new safety signals reported.

"We are disappointed that the significant increases in plasma PPi observed with BMN 401 did not translate into meaningful clinical improvements for children with ENPP1 deficiency," said Greg Friberg, M.D., Executive Vice President and Chief Research & Development Officer at BioMarin. "We are actively evaluating these data to determine the appropriate next steps. ENPP1 deficiency is a devastating disease, particularly for infants, where mortality rates remain high and new treatment options are urgently needed. We are deeply grateful to the children, families, investigators and study teams who are participating in this trial."

Detailed results from the ENERGY 3 study will be presented at an upcoming medical meeting.

About BMN 401 and ENERGY 3

BMN 401 (formerly INZ-701) is a potential first-in-class, subcutaneous enzyme replacement therapy for the treatment of people with ENPP1 deficiency.

ENERGY 3 is a Phase 3 multicenter randomized (2:1) controlled open-label clinical trial designed to evaluate the efficacy and safety of BMN 401 in children ages 1-12 with ENPP1 deficiency. Change from baseline in PPi through week 52 and RGI-C global score at week 52 are co-primary endpoints in this study. Following discussions with health authorities, RGI-C was added as a co-primary endpoint to assess clinically meaningful functional improvement in children with ENPP1 deficiency.

Key secondary endpoints include change from baseline in Rickets Severity Score (RSS), change from baseline in growth Z-score (height/body length and weight), and measurements of BMN 401 serum concentration and enzyme activity. Enrollment in ENERGY 3 was completed in January 2025, with the inclusion of 27 pediatric participants.

For more information, please visit clinicaltrials.biomarin.com.

About ENPP1 Deficiency

ENPP1 deficiency is a rare and lifelong genetic condition caused by changes in the ENPP1 gene, leading to progressive damage to blood vessels, soft tissues and bones. Infants with this condition are often diagnosed with generalized arterial calcification of infancy (GACI) Type 1, and about 50% of them do not survive beyond six months. Children with ENPP1 deficiency typically develop a type of rickets called autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adolescents and adults may develop osteomalacia (softened bones), both of which may cause pain and difficulty with movement. Individuals may also experience hearing loss, calcification in arteries and joints, and heart problems.

About BioMarin

BioMarin is a leading, global rare disease biotechnology company focused on delivering medicines for people living with genetically defined conditions. Founded in 1997, the San Rafael, California-based company has a proven track record of innovation, with a portfolio of commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that have a profound impact on patients. To learn more, please visit www.biomarin.com.   

Forward-Looking Statements

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including without limitation, statements about: BioMarin's plans and expectations regarding the BMN 401 program generally, and the pivotal Phase 3 ENERGY 3 trial results particularly; the safety profile and potential benefits of BMN 401; and BioMarin's plans to share detailed results from the ENERGY 3 study at an upcoming medical meeting. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others, any potential adverse events observed in the continuing monitoring of the patients in the clinical trials; the content and timing of decisions by the U.S. Food and Drug Administration, the European Medicines Agency, the European Commission and other regulatory authorities; and those factors detailed in BioMarin's filings with the Securities and Exchange Commission (SEC), including, without limitation, the factors contained under the caption "Risk Factors" in BioMarin's Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, as such factors may be updated by any subsequent filings with the SEC. Investors are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise.

BioMarin^® is a registered trademark of BioMarin Pharmaceutical Inc.

Contacts:
Investors	Media
Traci McCarty	Andrew Villani
BioMarin Pharmaceutical Inc.	BioMarin Pharmaceutical Inc.
(415) 455-7558	(628) 269-7393

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SOURCE BioMarin Pharmaceutical Inc.

FAQ

What did BioMarin (BMRN) announce about the Phase 3 ENERGY 3 trial for BMN 401 on May 18, 2026?

BioMarin announced top-line Phase 3 ENERGY 3 results for BMN 401 in children with ENPP1 deficiency. According to BioMarin, the trial met one co-primary endpoint on plasma PPi but showed no improvement in key radiographic and clinical endpoints, including RGI-C and growth measures.

Did BioMarin’s BMN 401 meet the primary endpoints in the ENERGY 3 Phase 3 trial (BMRN)?

BMN 401 met one of two co-primary endpoints in ENERGY 3. According to BioMarin, treatment significantly increased plasma PPi through week 52 versus control, but there was no improvement in Radiographic Global Impression of Change (RGI-C), an important measure of rickets severity in affected children.

What were the secondary endpoint results for BMN 401 in BioMarin’s ENERGY 3 study for ENPP1 deficiency (BMRN)?

Secondary endpoints did not show positive trends. According to BioMarin, measures such as Rickets Severity Score (RSS) and growth Z-scores for height/body length and weight failed to demonstrate improvement, leaving uncertainty about the overall clinical benefit of BMN 401 in this pediatric population.

How safe was BMN 401 in the Phase 3 ENERGY 3 trial reported by BioMarin (BMRN)?

BMN 401 was generally well-tolerated in the trial. According to BioMarin, no new safety signals were observed in children aged 1-12 with ENPP1 deficiency over 52 weeks, suggesting a manageable safety profile despite limited evidence of clinical efficacy from radiographic and secondary endpoints.

What are the next steps for BioMarin’s BMN 401 program in ENPP1 deficiency after the ENERGY 3 trial (BMRN)?

BioMarin is actively evaluating the ENERGY 3 data to determine appropriate next steps. According to BioMarin, detailed results will be presented at an upcoming medical meeting, and decisions on the BMN 401 program will consider the biomarker gains versus the lack of demonstrated clinical improvement.

How do the ENERGY 3 Phase 3 results affect the outlook for treating ENPP1 deficiency with BMN 401 (BMRN)?

The outlook is mixed, with biomarker improvement but limited clinical impact shown so far. According to BioMarin, significant plasma PPi increases did not translate into better RGI-C scores or secondary outcomes, so the potential role of BMN 401 in ENPP1 deficiency remains under review.