HanAll Biopharma Co., Ltd. has initiated its phase 3 VELOS-4 trial evaluating tanfanercept ophthalmic solution 0.25% for the treatment of moderate to severe dry eye disease (DED).
Let’s start with a company refresh.
A global biopharmaceutical company based in Seoul, South Korea—with U.S. operations in Rockville, Maryland—HanAll Biopharma is developing a portfolio of medicines for the following diseases/therapeutic areas:
- Endocrine diseases
- Circulatory diseases
- Urologic diseases
- Ophthalmology
- Oncology
- Neurology
Most notable in its ophthalmology portfolio is HL161 (batoclimab), the company’s lead candidate for autoimmune diseases such as thyroid eye disease (TED).
Plus: HL036 (tanfanercept)—our topic of discussion—is currently under investigation in clinical trials within the U.S. and China for DED.
Now give me more on tanfanercept.
Tanfanercept is a novel, potentially first-in-class, topical anti-inflammatory tumor necrosis factor alpha (TNF-α) inhibitor protein and molecularly-engineered TNF receptor 1 (TNFR1) that utilizes proteinases to resist degradation.
Note: TNF-α is known to be a major cytokine that regulates inflammatory responses associated with DED.Also: This asset was co-developed with South Korea-based Daewoong Pharmaceutical.
About this phase 3 trial … didn’t we already have data reported?
Yes, we did; however, that was for the phase 3 VELOS-3 (not VELOS-4, mind you) trial.
The company reported in May 2023 that the study had failed its primary endpoints, which included improvement at Week 8 from:
- Baseline in central corneal staining score (CCSS)
- Baseline in Eye Dryness Score via Visual Analog Scale (VAS)
Those findings?
Tanfanercept failed to demonstrate a statistical significance for both primary endpoints; however, it did meet its secondary objectives. Read our coverage here.
Gotcha. Now on to this VELOS-4 study …
The phase 3 VELOS-4 trial (NCT06400589) is a multicenter, randomized, double-masked, vehicle-controlled study assessing the efficacy and safety of tanfanercept 0.25% and 1.0% vs a vehicle for DED.
- The participants: 750 DED patients (aged 18+) diagnosed at least 6 months prior
- The setup: Participants randomized into three groups:
- Tanfanercept 0.25% group
- Administered twice daily (BID) for 12 weeks
- Tanfanercept 1.0% group
- Administered BID for 12 weeks
- Placebo (vehicle) group
- Administered BID for 12 weeks
- Tanfanercept 0.25% group
- The study duration: 12 weeks
What’s being measured?
Primary endpoint is the Schirmer test, as measured by the number of participants with improvement from baseline in unanesthetized Schirmer (at 12 weeks).
Measured at 2, 4, 8, and 12 weeks, secondary endpoints include:
- Schirmer test
- Dry eye symptom assessment
- Visual analog scale (VAS)
- Conjunctival redness
- Corneal staining
Plus: an “other” outcome measure includes comfort score (also measured at the same time points as secondary endpoints, at post-baseline visits).
So what’s key about this study?
Interestingly enough, it’s utilizing key data from the VELOS-3 study.
While that study failed to meet its primary endpoints, it did report that tanfanercept demonstrated a “statistically significant improvement in the secondary endpoint of tear volume.”
This was measured by unanesthetized Schirmer testing in the tanfanercept group vs vehicle (at Week 8; p = 0.002), according to the company.
Anything else?
Yes! Per HanAll Bipharma, a post-hoc analysis on the VELOS-3 study also found that 13% of participants in the tanfanercept group exhibited a “Schirmer test improvement of at least 10 mm from baseline at Week 8.”This was also statistically significant (p=0.011) compared to the vehicle group (4%), the company reported.
Why is this important?
It all comes down to the FDA’s 2020 Draft Guidance on Dry Eye Development, which essentially gave the OK for including participants with a minimum 10 mm increase in Schirmer test response rate.
What this means: HanAll Biopharma is able to use its VELOS-3 secondary endpoints as an acceptable primary efficacy endpoints for approval.
And when can we expect data?
With the trial slated to conclude by August 2025, the company expects to release topline in H2 2025.