Upcoming events – Protagonist and Pfizer target rare diseases

Welcome to your weekly digest of approaching regulatory and clinical readouts. After a turbulent 2018 Protagonist Therapeutics could do with some good news, and in the second half of the year it will find out whether its new lead project, PTG-300, holds promise.

PTG-300 is a subcutaneous mimetic of hepcidin, a hormone that regulates iron homeostasis. It is being evaluated in the uncontrolled phase II Transcend trial in 84 patients with beta-thalassaemia – both non-transfusion-dependent and the more severe transfusion-dependent subtype.

The multiple-ascending dose study is testing PTG-300 at 3mg, 10mg or 20mg, with non-responders moving up to the next dose.

In the non-transfusion-dependent group the primary endpoint is the proportion of patients achieving an increase in haemoglobin of 1g or more; in the transfusion-dependent cohort the primary endpoint is reduction in transfusion burden.

There are no US-approved therapies for beta-thalassaemia, but the space is getting crowded. Just this week Bluebird Bio’s gene therapy Zynteglo got the go-ahead in Europe for transfusion-dependent patients, and it could get the FDA nod next year.

If PTG-300 succeeds it could provide a more convenient – and presumably cheaper – option. A more relevant competitor could be Celgene and Acceleron’s luspatercept, which is due a US approval decision in transfusion-dependent beta-thalassaemia in December. Meanwhile, La Jolla Pharmaceutical's rival subcutaneous synthetic hepcidin, LJPC-401, is set to yield phase II data in beta-thalassaemia next year.

Protagonist also plans to start developing PTG-300 in a second indication later this year. Its chief executive, Dinesh Patel, has told Vantage that the group is looking at diseases including polycythemia vera and hereditary haemochromatosis.

Protagonist’s stock has yet to recover from the apparent failure of its previous lead candidate, PTG-100, in ulcerative colitis, later found to be caused by mistakes made by a contract research organisation.

Nevertheless, Protagonist switched to a back-up candidate, PN-10943, which is in phase I. A win with PTG-300 would give the group a much-needed boost.

Pfizer’s DMD challenge

Sarepta has so far dominated Duchenne muscular dystrophy gene therapy, but investors will soon get an early indication of whether Pfizer is a worthy competitor. Pfizer is set to present data from a phase I trial of its gene therapy PF-06939926 at the Parent Project Muscular Dystrophy (PPMD) conference, being held in Orlando on June 26-30.

Pfizer gained the project through its acquisition of Bamboo Therapeutics in 2016. Like Sarepta’s SRP-9001, previously known as AAVrh74.MHCK7.micro-dystrophin, PF-06939926 employs a shortened version of the dystrophin gene that is affected in DMD patients.

To date, six patients have been treated in the study of PF-06939926, which will enrol 12 subjects aged 5-12 years in total. Two doses have so far been used: 1x10¹⁴ vector genomes (vg)/kg and 3x10¹⁴vg/kg. The primary endpoint of the trial is safety, but it is also evaluating microdystrophin expression in muscle biopsies, a marker that the therapy is working as intended.

At PPMD Pfizer is set to present data from biopsies taken at two and 12 months post-treatment, and the company will hope that the results can at least match those seen with SRP-9001.

Last year Sarepta caused excitement by reporting microdystrophin expression levels of 74-96%, depending on the analysis used. Still, the data with SRP-9001 come from just four patients so far, so there is plenty to play for.

Another competitor, Solid Biosciences, has stumbled on lacklustre efficacy and toxicity fears with its candidate, SGT-001. Meanwhile, Vertex just entered what is becoming a crowded DMD space, signing deals with Crispr Therapeutics and Exonics.

Sarepta is well ahead of the pack, having begun a 24-patient placebo-controlled trial of SRP-9001, with data due next year. Pfizer still has a chance to catch up, but its data will need to impress.