Upcoming events – Fibrogen and Alnylam look to broaden their horizons

Duchenne muscular dystrophy attracts a new entrant in pamrevlumab, while Alnylam awaits more pivotal data with givosiran.

Welcome to your weekly digest of approaching regulatory and clinical readouts. Fibrogen has numerous balls in the air as it advances its two assets, roxadustat and pamrevlumab. The latter is next due data in Duchenne muscular dystrophy (DMD), with a phase II trial in non-ambulatory patients expected to read out in April.

While Sarepta dominates early-stage DMD, with projects that aim to delay or arrest progression and disability, Fibrogen seeks to treat respiratory disability in patients who are unable to walk. This fits with the progress pamrevlumab has made so far in its lead indication, idiopathic pulmonary fibrosis.

Pamrevlumab is a MAb that blocks CTGF, a mediator in the progression of fibrosis thought to play a role in declining lung function in DMD, something that can lead to patients needing ventilator assistance. To test this hypothesis Fibrogen enrolled 22 non-ambulatory boys, with the hope of improving predicted forced vital capacity. Other respiratory endpoints will also be measured, along with skeletal muscular strength and cardiovascular function.

Any evidence of disease stabilisation should be seen as a success, the Leerink analyst Geoffrey Porges wrote. Given that this is a single-arm study, investors should treat the data with caution, but a positive result would justify moving pamrevlumab into phase III.

Fibrogen is already pressing into pivotal trials in pamrevlumab's lead indication, idiopathic pulmonary fibrosis, as well as in pancreatic cancer. DMD might be an easier nut to crack, given the unmet medical need and the FDA's low regulatory bar.

This was the case made by Mr Porges, who wrote that investors had not fully appreciated the chances of pamrevlumab's success in a DMD trial. Analysts have not forecast any sales in DMD, while 2024 expectations for idiopathic pulmonary fibrosis and pancreatic cancer sit at $354m and $10m respectively, according to EvaluatePharma sellside consensus.

Study Setting Trial ID
FGCL-3019-079 Pamrevlumab in 22 non-ambulatory patients with Duchenne muscular dystrophy NCT02606136

Alnylam Envisions success

Meanwhile, Alnylam will see more data in March from the pivotal Envision trial of its second RNA interference project, givosiran. A win should support approval in acute hepatic porphyrias, unless safety worries resurface.

Alnylam posted positive early biomarker data from the trial last year, but disappointed investors who had hoped for a quick approval based on these results alone. There were also concerns about an imbalance of serious adverse events, with one patient discontinuing after an increase in liver enzymes.

Next, Alnylam will report topline data on the primary endpoint, improvement in annualised rate of porphyria attacks after six months of subcutaneous givosiran over placebo. Full results from Envision are expected at the Easl meeting in Vienna on April 10-14.

Alnylam has already begun a rolling submission with the US FDA for givosiran; if Envision is positive it hopes to complete this by mid-2019, with an eye on approval by the end of this year or early 2020.

Acute hepatic porphyrias are a group of rare inherited diseases characterised by life-threatening attacks involving severe abdominal pain, vomiting and sweating. The only available treatment for acute hepatic porphyrias is haematin, which must be given via intravenous infusion.

Givosiran is designed to prevent the translation of the ALAS1 protein, which in turn lowers levels of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG), substances that build up in acute hepatic porphyrias and are thought to cause acute attacks as well as chronic symptoms such as pain.

The September update showed a reduction in ALA with givosiran after three months' therapy. Envision is also evaluating ALA and PBG at six months, as well as other measures such as pain and fatigue.

The trial required patients to have experienced at least two attacks in the six months before enrolment. EvaluatePharma sellside consensus puts givosiran sales at $397m in 2024.

Leerink analysts give the project an 80% chance of success. However, more concerns around safety could put pressure on Alnylam’s stock.

Share This Article