Interview: Spain's Sanifit Set For Significant 2020
Calciphylaxis Drug In Phase III
Executive Summary
The Mallorca-based biotech is building a strong data package for SNF472 which the company believes will be an effective treatment for a number of calcification disorders in dialysis patients.
Spanish biotech Sanifit has begun a Phase III trial with what could be the first therapy for calciphylaxis, a rare disease which leads to the death of around 55% of patients within the first year of diagnosis.
The Mallorca-based firm, which focuses on treatments for calcification disorders, has announced that the first patient has been dosed in its pivotal trial of lead asset SNF472. The Phase III CALCIPHX study will assess the effect of SNF472, an intravenous formulation of myo-inositol hexaphosphate, when added to background care for the treatment of patients with calciphylaxis (also known as calcific uremic arteriolopathy) who have end-stage renal disease (ESRD) and are being treated with hemodialysis.
The trial, the endpoints for which will be improvement in wound healing and pain, consists of a double-blind, randomized, placebo-controlled period of 12 weeks followed by an open-label active treatment period of another 12 weeks. The study, to be conducted in the US and Europe, will enroll 66 patients and the topline readout is scheduled for 2022.
Sanifit CEO Joan Perelló told Scrip that SNF472 was the first molecule to come out of a Spanish university (the firm was founded in 2007 as a spin-off of the University of the Balearic Islands) to make it into Phase III trials. The drug tackles the underlying cause of calciphylaxis, namely severe calcification affecting the arterioles of the skin, and has been granted orphan drug designation by the US Food and Drug Administration and the European Medicines Agency in this indication.
However Sanifit believes that SNF472 has potential in a number of other indications with wider patient populations. In November, the firm presented positive topline results at the American Heart Association meeting in Philadelphia, which were published in the AHA's journal Circulation, of the Phase IIb CaLIPSO trial showing that the drug significantly reduced progression of coronary artery calcium (CAC) volume compared with placebo.
Perelló said that CaLIPSO, which enrolled close to 300 patients, showed that "the compound is doing what we always said it was doing: it significantly reduces progression of cardiovascular calcification, and the mechanistic promise is not just a promise anymore." Safety-wise, serious adverse events occurred in 38 patients (41%) in the SNF472 300mg group and 55 patients (60%) in the 600mg group, but the occurrence in the placebo group was also high, 49 patients (54%).
Perelló noted that "this is a very sick population, they have many comorbidities," so adverse events were expected in both arms "but we have not identified any safety signals so far." CaLIPSO also looked at major cardiovascular issues such as myocardial infarction, stroke or heart failure and there were fewer events seen in the active groups at both the low and high doses of SNF472 than in the placebo arm, though Perelló stressed that the study was not powered to evaluate cardiovascular vascular events.
The wealth of data that Sanifit has generated means that the company is exploring other indications as "all these calcium-related conditions in dialysis remain as unmet medical needs," the CEO pointed out. The risk of death is up to 30 times higher in dialysis patients and "this is not a minor thing," he added, noting that at least three studies from other companies attempting to address the problem of cardiovascular disease in dialysis patients have failed.
"The problem in dialysis is not the same problem that we have in the general population, this is about solid calcium build-up in the arteries that happens more rapidly in this patient population, it's a completely different approach," Perelló said.
One of the other indications that will be pursued is peripheral arterial disease (PAD), an accelerated cardiovascular calcification in the femoral arteries that supply blood to the legs, contributing to narrowing and hardening of these vessels and high mortality and morbidity. There are more than three million ESRD patients on dialysis, with 15-20% of them suffering from PAD and Perelló said a cross-sectional study evaluating SNF472 would begin late 2020/early 2021, noting that "nobody has conducted trials to address this indication.”
Last summer, Sanifit completed a €72.2m financing, the largest by a private biotechnology company in Spain. Perelló noted that the firm would need additional cash and "we are looking at all our options while sources of non-diluted financing could also play a role in order to advance our programs."
In terms of potential partners, he noted that there has been a lot of interest and "we are in touch with several players in this industry. Having presented data showing very meaningful effects in reducing the calcification progression, that raises interest both on the pharma and investor sides."
When Sanifit was founded, "there was no Spanish ecosystem in life sciences, " he told Scrip, "but now I believe we have about 10 specialized VCs in the sector and five of them have invested in Sanifit, plus international investors. This is powerful and allows us to keep developing what we are doing. Calcification disorders in dialysis patients are a huge problem, others have failed, but SNF472 has shown it has the potential to treat many of them."