Updates on Investigational Drugs Targeting Symptoms of Porphyria: Clinical Trials

Updates on Investigational Drugs Targeting Symptoms of Porphyria Clinical Trials

Porphyria is a group of disorders resulting from a buildup of natural chemicals that generate porphyrin in the body. Essential for the function of hemoglobin, that protein in the red blood cells that links to porphyrin, binds with iron and carries oxygen to organs and tissues. With the rise of porphyrins, comes significant health issues. With no cure and few therapy options addressing the symptoms of this rare, inherited blood disorder, nothing addressed the underlying root cause of the disease. With clinical trials, the hope is that researchers can develop new and better therapies. TrialSite News summarizes some recently active later-stage clinical trials.

Clinical Trials

A number of porphyria clinical trials are occurring at universities and medical centers around the world. Recently, Porphyria News reported on clinical trials and offered a link to Clincialtrials.gov, which reveals that a total of 47 clinical trials targeting porphyria have been conducted in total.

TrialSite News sought to understand a subset of active studies for the audience. A total of 13 are deemed active.  Only two of the clinical trials were in the important Phase III stage, that is, further down the pipeline toward U.S. Food and Drug Administration (FDA) approval. What follows is a summary of these studies.


In study NCT03338816, sponsor Alnylam Pharmaceuticals evaluates its drug givosiran (ALN-AS1) as compared to a placebo on how the investigational treatment might impact the rate of porphyria attacks in patients with Acute Hepatic Porphyrias (AHP). The core study was completed in April 2019 and reported the following:

·         Givosiran achieved a 74% mean reduction in composite annualized attack rate (AAR) relative to placebo, with consistent reductions across all components of composite endpoint and subgroups.

·         Treatment effect included a 90% median decrease in composite AAR relative to placebo, with 50% of Givosiran patients attack free

·         99% of patients enrolled in open-label extension study

The sponsor presented the clinical data at an oral presentation at the European Association for the Study of the Liver (EASL) International Liver Congress™ held last year. Amy Simon, MD, was the study director for the drug.

What is Givosiran?

This is an subcutaneously administered RNAi therapeutic targeting aminolaevulinic acid synthase 1 (ALAS1) in development for the treatment of acute hepatic porphyria (AHP). The sponsor suggests that monthly administration of the investigational drug has the potential to significantly lower induced liver ALAS1 in a sustained manner and thereby decrease neurotoxic heme intermediaries, aminolaevulinic acid (ALA) and porphobilinogen (PBG), to near normal levels. By reducing the accumulation of these intermediaries, givosiran has the potential to prevent or reduce the occurrence of severe and life-threatening attacks, control chronic conditions, as well as decrease the burden of disease.

The U.S. FDA granted the application of givosiran breakthrough therapy designation, priority review designation and orphan drug designation. With a trade name of Givlaari, the U.S. FDA granted approval to market the drug to Alnylam Pharmaceuticals in 2019. Porphyria News offers a breakdown of Givlaari

MT-7117 (Dersimelagon) from Mitsubishi Tanabe Pharma

The Japanese pharmaceutical company Mitsubishi Tanabe Pharma Development America, Inc. initiated a Phase 3 clinical trial numbered NCT04402489 in June 2020. This is a parallel assignment, triple masked, multicenter, randomized, double-blind placebo-controlled clinical trial in which researchers seek to investigate the efficacy of MT-7117 on time to onset and severity of first prodromal symptoms (burning, tingling, stinging) associated with sunlight exposure in subjects with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria aged 12 to 75 years of age. Conducted at a dozen or so sites, the study builds on the success of previous studies.

What is MT-7117?

Dersimelagon is a novel synthetic, orally-administered, non-peptide small molecule, which acts as a selective agonist of melanocortin-1 receptor (MC1R) with a potential for being effective in the prevention of phototoxicity in EPP patients. Developing to target EPP, Dersimelagon (MT-7117) is an investigational medication not approved by the FDA or any other global regulatory authority. The sponsor received Fast Track Designation by the U.S. FDA for the drug in June 2018.

Update from Karolinska Institutet’s Study of Hemin

Last year, Karolinska Institutet completed a study, published in The New England Journal of Medicine, revealing a clinical trial involving a treatment called Hemin. Study lead author Eliane Sardh, a researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet, reported Hemin “will continue to be important, but its only for acute treatment.” The investigator reported as well that “For patients with recurrent attacks, no other curative treatment is available than liver transplantation.”

Call to Action: To those in our TrialSite Network: are you interested in earlier Phase 1 or 2 clinical trials targeting Porphyria? Contact us.