Upcoming events – Mid-stage and confirmatory results from Global Blood and Catalyst

Welcome to your weekly digest of approaching regulatory and clinical readouts. Global Blood Therapeutics will report mid-stage data by the year’s end on GBT440 in idiopathic pulmonary fibrosis, an indication where success could bring upgrades, since current forecasts only cover sickle cell disease.

Having been hit with a refusal to file for Firdapse earlier this year, Catalyst needs a win in its latest phase III study in Lambert-Eaton myasthenic syndrome, a rare autoimmune neuromuscular disorder, to satisfy the regulators. Discussions over pricing Firdapse, a contentious orphan drug whose active ingredient has been used for many years unlicensed, will be a bigger debate.

Another string to its bow

The current quarter should yield data from three trials of Global Blood’s GBT440, which works by increasing haemoglobin’s affinity for oxygen, and is being tested in hypoxaemia – abnormally low levels of oxygen in the blood – in patients with idiopathic pulmonary fibrosis (IPF).

The studies comprise the single-arm phase II Zephyr trial in 16 adults who needed oxygen when resting, who were given 900mg GBT440 daily for 90 days. The primary measure is change in oxygen saturation from baseline, and secondary endpoints include the six-minute walk test, patient related outcomes, pulmonary function tests and adverse events.

A second phase II, a double-blind test, is in 30 adults with less severe disease who had low blood oxygen when exercising, looking at 600mg or 800mg versus placebo, once daily for 28 days. This primarily examines adverse events, but secondary measures include pharmacokinetics and oxygen saturation at rest and after exercise. Needham analysts note that a 3% difference in oxygen saturation versus placebo would be meaningful.

The last trial is a phase I study, Basecamp, in 20 healthy volunteers, looking at oxygen saturation during rest and exercise under hypoxic conditions, such as those experienced at higher altitudes.

Sickle cell disease is the compound’s lead indication, with a registrational phase III trial to report in 2019, though in this indication the project showed mixed results in phase II (Therapy focus – Sickle cell therapies creep closer to market, June 16, 2016).

EvaluatePharma sellside consensus puts 2022 sickle cell revenue at $464m, including partnering outside the US. GBT440 has an NPV of $1.7bn, well above Global Blood’s market cap. Morgan Stanley analysts expect a 10-25% stock movement either way, depending on the IPF data.

Catalyst’s catalyst

Catalyst’s shares fell 37% in February when it got its US refusal to file letter for Firdapse, with the FDA calling the application incomplete. The regulators requested short-term confirmatory and abuse liability studies before resubmission.

The latest trial due to report in the fourth quarter is in 28 adults with Lambert-Eaton myasthenic syndrome, a rare autoimmune, neuromuscular disorder characterised by progressive muscle weakness of the limbs – the same indication that was previously rejected.

The study has the same co-primary endpoints as its previous phase III: quantitative myasthenia gravis score and global impression score. Firdapse was given three to four times a day for four days versus placebo in the randomisation period. 

The first phase III had a discontinuation design with 38 patients given Firdapse for at least 91 days and then assigned to Firdapse or placebo for two weeks. Patients then received open-label Firdapse for two years. At day 14 the change in quantitative myasthenia gravis score only just reached statistical significance, with a p value of 0.0452. The change in global impression was more stongly significant, with p=0.0028.

Firdapse, or 3,4-diaminopyridine phosphate, gained approval in the EU in 2009 and is promoted there by Biomarin. It had previously been used unlicensed for many years in its base form, 3,4-diaminopyridine. Last year Biomarin reported sales of $18m, and EvaluatePharma 2022 consensus forecasts sit at $166m, with $147m assigned to Catalyst.

In the US Jacobus Pharmaceutical, a private company based in New Jersey, had for over 30 years provided 3,4-diaminopyridine to patients for free, and is now also running clinical trials. Catalyst also provides Firdapse for free under an expanded-access programme, but with its orphan drug designation the issue of price could become highly contentious.

To contact the writer of this story email Joanne Fagg in London at [email protected] or follow @ByJoFagg on Twitter