Dimerix (DXB: $0.35) is the recipient of a very valuable, potential change to the way that drug candidates are assessed for the treatment of FSGS (focal segmental glomerulosclerosis).
The PARASOL initiative was launched in December last year. Its aim is to remove the obstacles in finding one or more treatments for the orphan kidney disease FSGS.
The key findings are that a lower threshold in proteinurea, rather than what is considered a complete response, may be accepted by the FDA when assessing new drug candidates for this disease, with a range of proteinurea measures that may also be considered for traditional approval.
Traditional Measures Aren't Effective for FSGS
For kidney diseases, such as IgA nephropathy, drugs have previously received accelerated approval on the measure of proteinurea, with full approval after two years of therapy measuring the change in slope of eGFR (estimated glomerular filtration rate, i.e. filtration rate through the kidneys).
Challenges in Developing New FSGS Therapies
The problem with FSGS, which is characterized by scarring of the kidneys, is that eGFR is highly variable. And a complete response in proteinurea (measured as less than 0.3g/g in UPCR) is often not achievable.
More Appropriate Measures for Approval
Outcomes from the PARASOL initiative are that a response in FSGS patients to less than just 0.7g/g are "plausibly similar to complete remission". Another suggestion from the group is that even higher thresholds (up to 1.5g/g) may also represent "substantial biological improvement that slows disease progression for those at highest risk of progression."
The group has also suggested that another measure that could be considered as an endpoint in clinical studies is the number of patients achieving a 50% drop in proteinurea levels in more advanced patients.
Importantly, the PARASOL working committee included the FDA, as well as universities and kidney disease organisations. Dimerix is one of the sponsors of the initiative.
Implications for Dimerix
Dimerix is currently conducting a global Phase III study in FSGS which will involve over 170 clinical sites. Its study incorporates a blinded, interim assessment by the company in the first 144 patients who have been treated with its drug candidate, DMX-200, for 35 weeks. This is expected mid next year.
The company can now approach the FDA and discuss changes to its primary endpoints, which will need to occur prior to the unblinding of any data. Likely outcomes are changes to the threshold that can be considered a biologically and clinically meaningful result (i.e. UPCR levels of 0.7g/g, 1.0g/g or 1.5g/g, rather than the 0.3g/g level that has been considered as a complete response in proteinuria levels).
According to Dimerix's CMO David Fuller: "We are powered on eGFR but also now have the ability to look at proteinuria in many different ways."
As at the end of October, 129 patients had been recruited into Dimerix's Phase III study. The inclusion of a large clinical trial site network has favourable implications for rapid product adoption should regulatory clearance be secured in various regions.
Trial to Continue as Planned
Dimerix is currently recruiting patients across 17 countries. The current Phase III study, which will seek to recruit 286 patients, will continue to obtain eGFR data and proteinurea data with treatment for two years. The eGFR data may be important to secure approval in other regions such as Europe that may not accept proteinurea as a sole endpoint for approval.
What needs to be discussed now with the FDA are new proteinurea endpoints that might be considered and over what period is the effect considered to be a sustained response for full approval, as well as for conditional approval. Whether Dimerix may be able to achieve earlier full approval for DMX-200 in the US at this point is unclear.
All patients in the trial are offered to move into an open label extension study once treatment is complete (with DMX-200 or placebo), where they will receive DMX-200, with all patients opting to do so at this point.
Summary
The findings from the PARASOL study provides some highly beneficial options for Dimerix. These outcomes may provide more appropriate endpoints which should bring a higher probability of success.
According to CEO Nina Webster, the outcomes from the PARASOL initiative has accelerated partnering discussion globally.
Dimerix is capitalised at $193 million.
Bioshares recommendation: Speculative Buy Class A
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