Recently, aTyr Pharma reported results from its late-stage phase 3 EFZO-FIT study, which used its drug efzofitimod to treat patients with a type of interstitial lung disease [ILD] known as sarcoidosis. This late-stage study compared the use of either 3.0 mg/kg or 5.0 mg/kg of this drug to that of placebo in terms of the primary endpoint, which was to observe the change from baseline in average daily oral corticosteroid use. The primary endpoint ended up not being statistically significant with a p-value of p=0.3313. This release of data caused the stock price to close lower on Monday, September 15, 2025, by 83% to $1.01 per share.
The hope was that efzofitimod would be able to overcome placebo in terms of this primary efficacy endpoint, but with that not being obtained, it was the bad news for the day that caused the stock price to plummet. While this was not ideal, there is a glimmer of hope for the company, and this would be in terms of some positive findings that it was able to observe in patients who took the higher dose of 5.0 mg/kg of this drug. This all has to do with a scoring measure known as the King’s Sarcoidosis Questionnaire [KSQ]-Lung score. This is an important scoring measure because it looks at the overall health of the lung of the patient who has sarcoidosis.
That is, it measures several items ranging from coughing, breathlessness, and other problems dealing with the lung. With respect to this, there was a nominal p-value improvement with patients who took 5.0 mg/kg of efzofitimod compared to those who took placebo, with a p-value in place of p=0.0479. Furthermore, those who improved in terms of this KSQ-Lung Score ended up showing a greater withdrawal of the amount of steroids they needed to treat their disease. Both of these items are what aTyr Pharma is running with as improvements and believes that this will be enough to hold productive talks with the FDA. Despite the primary endpoint not being met, the company still wants to have a dialogue with the FDA about a possible path forward to bringing this drug to market.
Sarcoidosis is a collection of inflammatory cells that form granulomas in many parts of a person’s body, with the main ones being affected being the lymph nodes and the lungs. Speaking of which, when this inflammatory disorder affects the lungs, this is what is called pulmonary sarcoidosis. A bright side is that there are moments whereby a person can actually have this disorder and not be affected. In essence, the lung recovers on its own without any intervention. On the flip side, there is the aggressive nature of this disorder, which is where it continues to overwhelm the patient in a chronic way. This would be in terms of not being able to breathe effectively and causing other symptoms like coughing, chest pain, and a host of other symptoms.
Efzofitimod is an extracellular tRNA synthetase with the splice variant of histidyl-tRNA synthetase [HARS] and the main function is to target receptor protein neuropilin-2 [NRP2] which has an effect on vascular and lymphatic growth of blood vessels. What makes this drug highly ideal is the mechanism of action [MOA] to reduce inflammation present in lung disorders like sarcoidosis, but to do so without any type of immune suppression. It achieves this function by targeting activated myeloid cells, which are driven by NRP2.
It remains to be seen whether or not the FDA talks will be productive enough to allow the company to run another phase 3 study just using the higher 5.0 mg/kg dose of efzofitimod to treat these patients with sarcoidosis; however, there is another shot on goal for it. This would be in terms of another ongoing phase 2 EFZO-CONNECT study evaluating the use of this drug to treat patients with systemic sclerosis-related interstitial lung disease [SSc-ILD]. There was the release of interim data showing that this drug was able to help these particular patients in terms of skin thickness using a clinical tool known as the Modified Rodnan Skin Score [mRSS]. The higher the score, the worse the skin thickening that is present. In order for a drug to have achieved a meaningful outcome, it must be shown that there was at least a 4 to 6 point improvement in this score.
The company was able to show in its interim analysis that 3 out of 4 particularly diffuse SSc-ILD patients had a 4-point or greater improvement in this measure. While this is encouraging, I believe that these results should be taken with a grain of salt, and that is because this was a small group of patients for starters. Not only that, but this is in terms of skin thickening, whereas the whole goal of the study is to assess lung function as the primary endpoint of a 24-week period. The point being is that while the drug did well in terms of the mRSS, there is no guarantee that it will automatically translate to a successful outcome in terms of improving lung function for them.