BMRN Scraps BMN 401 After ENPP1 Trial Miss: $270M Lost

BioMarin Pharmaceutical (BMRN) officially ended development of BMN 401 across all indications on August 6, writing off the $270 million Inozyme Pharma acquisition completed in July 2025. The decision, disclosed alongside Q2 2026 earnings, comes three months after the Phase 3 ENERGY 3 trial missed one of two co-primary endpoints in ENPP1 deficiency.

BMN 401, a subcutaneous enzyme replacement therapy formerly called INZ-701, was tested in 27 children with ENPP1 deficiency, a rare genetic disorder that causes pathologic mineralization, including arterial calcification and a form of rickets. The trial met the biomarker endpoint: BMN 401 increased plasma inorganic pyrophosphate (PPi) levels through Week 52 versus conventional therapy. BioMarin called the increase statistically significant but did not disclose the magnitude or p-value. It missed the clinical endpoint of skeletal healing measured by X-ray. BioMarin acknowledged “no positive trends were observed” across secondary endpoints including rickets severity scores, body growth, and weight gain.

The Inozyme acquisition was the first major deal under Chief Business Officer James Sabry, the ex-Roche dealmaker hired in 2024. BMN 401 represented “substantially all” of the acquired asset value, meaning the entire $270 million purchase price evaporated in under 13 months. Guggenheim analysts had already pulled BMN 401 from their model in June, writing that “success is highly unlikely in light of these data.”

The write-off further narrows BioMarin’s pipeline, which has shed programs including its preclinical PKU gene therapy and now the entire ENPP1/ABCC6 deficiency platform. What cushions the blow is VOXZOGO. The achondroplasia drug generated $253 million in Q2 revenue, up 14% year over year, and management raised full-year 2026 guidance to at least $1 billion. The $4.8 billion Amicus Therapeutics acquisition added GALAFOLD and POMBILITI to the commercial rare disease stable.

But the risk is concentration. With BMN 401 written off and the PKU gene therapy program shelved, VOXZOGO is now the pipeline’s growth engine. The Amicus deal added GALAFOLD and POMBILITI, but both are mature products, not growth drivers. If the hypochondroplasia sNDA or the under-5 achondroplasia sNDA encounters regulatory friction, BioMarin’s growth narrative narrows to a single drug.

BMRN shares closed at $61.46 on August 6, market cap $11.9 billion. The stock absorbed the write-off because the bad news was telegraphed: the ENERGY 3 miss in May made discontinuation a matter of when, not if. Investors have since focused on VOXZOGO’s growth, including an sNDA for hypochondroplasia and a pending sNDA for children under 5 with achondroplasia.

What to watch: capital allocation. Management signaled it can “redeploy growth capital towards pipeline augmentation” within 12 to 18 months once the organic growth story is established. After the $270M Inozyme write-off and a second-quarter net income drop in part attributable to the impairment, investors will scrutinize whether the next M&A bet is on validated Phase 3 assets or earlier-stage programs with real biology behind them.

Source: BioMarin Q2 2026 financial results press release