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SynAct Pharma´s clinical trial application for AP1189 in Nephrotic Syndrome approved by the Danish Medical Agency

SynAct Pharma AB ("SynAct") today announced that the Danish Medical Agency has approved the company’s clinical trial application (CTA) for a Phase IIa study in idiopathic membranous nephropathy patients with Nephrotic Syndrome.

Uppdaterad 2020-06-02
Publicerad 2020-06-02

In the Phase IIa study, AP1189 will be tested in a double-blind, placebo-controlled multicentre study as add-on therapy to ACE-inhibitor or Angiotensin-2 receptor antagonists in a once-daily dose regimen for four weeks with the primary purpose to show treatment effect on urinary protein excretion relative to pre-treatment levels and placebo. The patients will be dosed with either 100 mg AP1189 or Placebo in a 2:1 randomization in up to 24 patients.

Nephrotic syndrome (NS) is a relatively rare condition characterized by loss of protein in the urine that is associated with development of edema, hypoalbuminia and elevated plasma lipids, ie development of NS. NS can further develop into chronic kidney disease and is associated with risk for development of hypertension and ischemic cardiovascular disease. 

Idiopathic membranous nephropathy (iMN), is one of the most common causes of Nephrotic Syndrome in adults. In most case, iMN is due to circulating antibodies against the M-type receptor of phospholipase 2 (Anti-PLA2r). These antibodies bind to the PLA2r on a specific cell type in the kidneys called podocytes thereby inducing morphological and functional changes in the kidneys resulting in high levels of protein in the urine.

Podocytes express melanocortin Type 1 receptors (MC1r) and it has been shown that MC1r stimulation preserved the structure of the podocytes and reduce proteinuria in experimental models of NS. In patients compounds as ACHTAR Gel with the MCr agonist ACTH as active ingredients have been shown to reduce proteinuria even in difficult to treat patients as patients with glucocorticoid resistant NS.

AP1189 is a biased MC1r and MC3r that in an animal models of NS mimicking iMN and have shown to induce treatment effect comparable to what has been reported for other MCr agonists and in a head to head study with ACTH showed superior treatment effect with significantly lower levels of proteinuria following 4 weeks treatment (Patent application no: WO/2019/243625)

First-line treatment of iMN is Angiotensin-converting-enzyme inhibitors or Angio­tensin II receptor blockers to control blood pressure and decrease the protein loss in the urine. If continued symptoms follow in six months, the patients will be treated with glucocorticoids, immunosuppressives, or ACTH. These treatment options are associated with often treatment-limiting side effects and a fraction of patients will despite treatment continue to have symptoms.  The market potential is considered very attractive with Mallinckrodt sales of 300 Mio. USD./year.[1]

There is therefore a need for new treatment options where AP1189 as a compound with anti-inflammatory and pro-resolving effects and the specific ability to stimulate the MC1r on the podocytes could be a new treatment option. CSO Dr. Thomas Jonassen highlights “SynAct Pharma has therefore decided to set up a proof of concept study in NS, where the first study will be in iMN patients. It would be possible at a later stage to broaden out the treatment to other diseases that cause NS, including minimal change disease (MCD) and focal segmental glomerulonephritis (FSGS). The global FSGS-market is estimated to rise 8.0% CAGR over the course of the forecast period from 2017 to 2025. Expanding at this pace, the market which was worth US$7.82 bn in 2016, is projected to attain a value of US$15.83 bn by 2025-end.[2] With the approval from the Danish Medicinal agency and an expected approval for the local Ethical Committee (where the handling of the application is delayed due to the Covid-19 pandemic), the company aim to initiate the Phase IIa-study in NS by the end of June 2020.”

Detailed information of the study will be available at www.clinicaltrial.gov following study initiation.

This information is such information that SynAct Pharma AB is obliged to publish in accordance with the EU Market Abuse Regulation. The information was submitted, through the agency of the below contact person, for publication on June 2, 2020.



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