Fibrogen picked an interesting time to reveal the terms of a chunky IPO. Only days previously its close competitor in the anaemia space, Akebia Therapeutics, lost a third of its market cap on the back of disappointing clinical data.
Akebia, which floated in March, has been left with a $263m valuation and a share price well below its float level. Fibrogen, meanwhile, hopes to raise $125m and achieve a market cap close to $1bn. Both are working on candidates that target hypoxia inducible factor prolyl hydroxylase (HIF-PH) and mid-stage data from the two firms suggest that this valuation difference is warranted; the fact that the latter has two big pharma partners only confirms this.
HIF-PH inhibitors work by mimicking the reaction of the body to high altitude and are considered exciting new oral treatment options for anaemia. The ultimate hope is that they will replace erythropoietin-stimulating agents (ESAs) like Epogen and Aranesp, which still generate billions of dollars of sales each year despite carrying serious safety issues and the need for transfusion.
Fibrogen is much further ahead with its candidate, FG-4592 or roxadustat. Six phase III trials have started in a huge programme expected to recruit up to 8,000 anaemic patients with chronic kidney disease (CKD), in both the pre-dialysis and dialysis settings. These are largely being driven and funded by AstraZeneca and Astellas, global partners on the project (Therapeutic focus – Big pharma takes high-level interest in anaemia pills, August 28, 2013).
Fibrogen says the programme is already fully funded through to launch; proceeds from the planned IPO are targeted at the rest of its pipeline.
Akebia, meanwhile, raised $115m in its IPO and has sufficient funds until the first half of 2016. It just completed a phase IIb trial of AKB-6548, the results from which were released earlier this week, and says it still intends to launch global phase III registration studies next year.
It is clear that Akebia will need more cash to fulfil these ambitions. By comparison, to help fund its pivotal programme Fibrogen points to more than $500m in up-front payments due before any US approval, on top of the development cost reimbursements negotiated under the deals.
Unfortunately for Akebia, the data released earlier this week will not make raising this cash – or attracting a partner – any easier.
Its study recruited 209 pre-dialysis patients with anaemia related to CKD, who were given either AKB-6548 once daily or placebo. On paper the study was a success – 54.9% of patients who received AKB-6548 met the primary endpoint versus 10.3% in the placebo group (p<0.0001). The primary endpoint was defined as achieving or maintaining certain haemoglobin levels.
However, compared with mid-stage results from Fibrogen, this efficacy does not look that impressive. Fibrogen ran a 16-24 week study that recruited 145 patients and found that 93% of those treated with roxadustat had a haemoglobin response; this was also defined as achieving or maintaining certain haemoglobin levels, similar to those used by Akebia in its trial.
Admittedly, Fibrogen’s study was a single-arm, open-label trial, so was nowhere near as rigorous as Akebia’s placebo-controlled study. And the numerous caveats to comparing between trials – including recruiting different types of patient – are of course relevant here.
But these efficacy comparisons were compounded by safety worries: Akebia revealed a higher incidence of serious adverse events in the active arm, one of which was considered probably related to active treatment, while two were possibly related, including one death. Two further deaths on active treatment were not considered to be related.
On a conference call, Akebia’s management team brushed off concerns, and said the one death that was related involved a patient with multiple cardiac problems who died of a heart attack. The investigator “took a cautious stance” and judged it possibly related to AKB-6548, executives said, expressing their confidence that overall the signals seen were nothing unexpected from a very sick patient population.
Fibrogen has of course seen adverse events in its trials. But with two big pharma partners on board, roxadustat is the yardstick by which AKB-6548 will be measured, rightly or wrongly.
For any chance of catching up to Fibrogen, Akebia needs to make a much stronger case for AKB-6548.