QPI-1007 (cosdosiran), a siRNA compound, is a neuroprotective drug candidate under development for Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) and other neuropathies, including glaucoma. QPI-1007 works by reducing the expression of the pro-apoptotic gene caspase 2. QPI-1007 has completed three clinical studies, including a multinational, randomized, double-blind, sham-controlled Phase 2/3 QRK207 trial for the treatment of NAION. QPI-1007 has been granted an Orphan Drug designation by the FDA for the NAION indication.

Drug Product

QPI-1007 is a synthetic, chemically-stabilized, double-stranded siRNA, targeting the expression of the pro-apoptotic gene caspase 2 via the RNA interference (RNAi) mechanism. The compound is designed to allow high and specific RNAi activity while attenuating off-target and immunostimulatory effects. QPI-1007 is being developed as a neuroprotectant to mitigate the apoptotic death of retinal ganglion cells (RGCs).

Mechanism of Action and Non-clinical Studies

Caspase 2 is a member of a family of pro-apoptotic peptidases which is uniquely positioned in the apoptosis pathway, integrating receptor-induced and mitochondrial apoptosis. Inhibition of caspase 2 expression by siRNA in the retina of affected eyes confers ocular neuroprotection.

Nonclinical studies have demonstrated the activation of caspase 2 in RGC; the uptake of siRNA in retinal ganglion cells following intravitreal administration; RNAi-mediated mechanism of action for QPI-1007 in retina ocular tissues harvested after intravitreal administration, and activity of QPI-1007 in models involving RCG loss [Ahmed Z, et al, Cell Death Dis. 2011,;2:e173; Vigneswara V et al, Brain. 2014; 137(Pt 6):1656-75; Lidster K et al. PLOS One. 2013; 8(11):e79188; Thomas et al, Invest Ophthalmol Vis Sci. 2018; 59(11):4453-4462].

Furthermore, QPI-1007 exhibited a favorable safety profile in non-clinical toxicology studies.

Non-Arteritic Ischemic Optic Neuropathy (NAION)

NAION is the most common Ischemic Optic Neuropathy (ION) and the most common cause of sudden optic nerve-related vision loss in patients over the age of 50. The reported incidence of NAION in the US is 2.3-10.3 per 100,000 persons over the age of 50 [Johnson LN, Arnold AC; J Neuroophthalmol; 1994; 14: 38-44; Hattenhauer et al Am J Ophthalmol; 1997 123(1):103-7.].

NAION is episodic in nature, characterized by an acute-onset, painless, unilateral vision loss. NAION results from optic nerve ischemia which may stem from overall poor circulation, thrombosis, or embolism. Initial visual loss is caused by optic nerve injury and retinal edema followed by slow secondary RGC death. Once vision is lost, there is little chance of fully regaining it [Hayreh et al. Am J Ophthalmol. 2001; 132(5):734-42]; moreover, further deterioration in visual acuity is observed in the first months following the initial insult. Fifteen percent of patients with NAION develop the disease in the other eye within 5 years [Newman et al, Am J Ophthalmol.2002;134:317–28.].

Most optic neuropathies do not have adequate therapeutic options. Many of these conditions, including NAION, remain unmet medical needs and are usually managed using corticosteroids. An ocular neuroprotective agent is expected to reduce vision loss occurring over time after ischemic insult to the optic nerve by preserving RGCs.


Similar to NAION where RGC and vision loss happen during the first 3-6 months after the initial insult, glaucoma, a chronic optic neuropathy, also results in loss of RGCs, albeit more gradual.

Glaucoma is one of the leading causes of blindness and vision impairment worldwide and the leading cause of irreversible blindness [Flaxman SR et al, Lancet Glob Health 2017; 5: e1221–34; Weinreb RN et al, JAMA. 2014 May 14; 311(18): 1901–1911]. Glaucomatous neuropathy is the ultimate pathway of Primary Open Angle Glaucoma (POAG). The hallmark of glaucomatous neuropathy is damage to the optic nerve head and Visual Filed (VF) loss secondary to apoptosis of Retinal Ganglion Cells (RGCs) and their axons leading to irreversible visual loss [Almasieh M et al, Prog Retin Eye Res. 2012 Mar;31(2):152-81; Agarwal R et al, Indian J Ophthalmol. 2009 Jul-Aug; 57(4): 257–266].

The current standard of treatment for glaucoma is directed at decreasing intraocular pressure (IOP). The Collaborative Normal Tension Glaucoma Study has shown that a reduction of at least 30% in IOP slows the rate of vision loss. However, glaucoma may still progress with patients continuing to suffer from further clinical vision loss, even if IOP is controlled successfully [Anderson 2003].
As a neuroprotective agent, QPI-1007 has the potential to preserve vision and prevent macular and nerve fiber layer loss in a population of IOP-controlled glaucoma patients.

Clinical Studies

QPI-1007 is being evaluated in multiple clinical trials, as summarized in the table below.

Indication Phase # of Subjects Key Assessments Status
Legally Blind Phase 1
N=18 Safety, tolerability and pharmacokinetics Completed
NAION Phase 1/2
N=30 Safety, tolerability and
Phase 2/3 (QRK207) N=732 Safety, efficacy Completed

QPI-1007 demonstrated the following outcomes during nonclinical and clinical studies:


  • Evidence of clinical activity in patients with compromised vision at presentation.
    • QPI-1007 treated patients were less likely to experience a 7dB loss in visual field (VF-MD) vs. sham at 6 months
    • QPI-1007 treated patients were less likely to experience 10-letter loss in visual acuity vs. sham at 6-months
  • No safety issues or dose limiting toxicity identified in over 500 subjects receiving single or multiple intravitreal injections.


  • The utility of QPI-1007 for neuroprotection in glaucoma is supported by proof-of-concept studies in nonclinical glaucoma model and evidence of clinical effect in the glaucoma approvable endpoints from the NAION trial.

What’s Next for QPI-1007

Design QPI-1007 NAION pivotal trial and plan clinical development in Glaucoma.