Efzofitimod missed the primary endpoint in the Phase 3 EFZO-FIT study, reducing mean daily oral corticosteroid dose at week 48 to 2.79 mg versus 3.52 mg on placebo (p=0.3313). Nominal findings favored the 5.0 mg/kg dose on multiple measures: complete steroid withdrawal at week 48 in 52.6% versus 40.2% (p=0.0919), improvement in KSQ-Lung score (10.36 versus 6.19; p=0.0479), and a composite of complete steroid withdrawal with KSQ-Lung improvement in 29.5% versus 14.4% (p=0.0199). Forced vital capacity was maintained across arms (absolute percent predicted change −1.81 versus −2.11; p=0.7875). Safety was consistent with prior experience and generally well tolerated.
The core development is a Phase 3 readout in 268 patients with pulmonary sarcoidosis comparing efzofitimod 3.0 mg/kg and 5.0 mg/kg to placebo over 48 weeks with a protocolized steroid taper in the first 12 weeks and continued taper or rescue through week 48. The hierarchical statistical plan means that, with the primary endpoint not met, subsequent p-values are nominal. The company intends to meet with the FDA to discuss whether the observed signals in patient-reported outcomes and steroid withdrawal can support a path forward in a setting with no approved therapies.
Strategically, this is a pivot under constraint. The program was anchored on steroid-sparing as the primary regulatory story, but a high placebo response under a tightly guided taper compressed separation. That design choice improves operational control and site consistency but can elevate placebo performance, a familiar tension in steroid-reduction trials. The company will now emphasize quality-of-life gains and a composite of steroid withdrawal plus KSQ-Lung improvement, positioning efzofitimod as a way to reduce steroid burden without compromising lung function. The challenge is regulatory: these effects were not multiplicity-controlled, and the FDA’s willingness to accept a PRO or composite as a registrational endpoint in sarcoidosis remains untested at scale. Any argument will have to link PRO improvement to meaningful clinical change and real steroid minimization, ideally supported by prespecified analyses and durability.
For sites and CROs, EFZO-FIT demonstrates that a global, multicenter sarcoidosis RCT with an aggressive, protocolized steroid taper is feasible and can be executed without deterioration in FVC. That will influence future protocol design, taper schedules, and rescue criteria, as well as the operational importance of accurate steroid dosing capture and high-quality PRO collection. Sponsors in sarcoidosis and adjacent ILDs will take note: endpoint selection and taper architecture can drive placebo performance, and composite endpoints pairing steroid-sparing with patient-reported benefit may better reflect clinical priorities but require early validation and regulatory buy-in. For patients, the near-term impact is limited; for partners and regional developers, including those in Japan, the path to approval likely now depends on reframing endpoints or running another study.
The next inflection point is FDA feedback on whether a PRO-driven or composite endpoint could anchor a registrational strategy and what, if any, additional trial is required. Watch for dose selection clarity between 3.0 and 5.0 mg/kg, subgroup and regional analyses to explain variability, durability of KSQ-Lung and steroid-withdrawal effects beyond 48 weeks, and any biomarker or imaging data that link symptom improvement to disease modification. Presentation of full data at ERS later this month should signal how convincingly the totality of evidence can be marshaled; absent regulatory openness, a follow-on trial with a composite or PRO primary and refined taper design may be unavoidable.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
