Welcome to your weekly roundup of approaching clinical readouts. Bayer and Merck & Co’s high-stakes decision to advance the heart failure project vericiguat into phase III paid off late last year with success in the Victoria trial. However, in an increasingly competitive chronic HF space the drug might need to distinguish itself further to become commercially successful.
This is why the phase II Vitality-HFpEF trial has taken on significance. Despite vericiguat's new-found effectiveness as an add-on to standard of care, one of its biggest issues will be finding a place in chronic HF treatment protocols. Just look at Novartis’s Entresto, which had a disappointing launch and only really took off with changes to treatment guidelines.
The Victoria readout only included topline results in chronic HF with reduced ejection fraction; detailed numbers are expected at a medical conference later this year. If the asset does not come up with a 20% reduction in the risk of HF hospitalisation or cardiovascular death on top of standard of care it will suffer versus Astrazeneca’s SGLT-2 Farxiga, which has performed strongly here.
This is where Vitality-HFpEF comes into play; in the 788-subject trial vericiguat is being tested in the much tougher setting of HF with preserved ejection fraction (HFpEF), where the market leader, Entresto, has failed.
More significantly, Vitality-HFpEF has patient-reported quality of life measures as its primary endpoint. Patients in the more advanced stages of the disease often suffer severe limitations to daily activities and significant anxiety about their health, making this an important measure of effectiveness.
The hope is that success in Vitality-HFpEF will open up a new HFpEF patient population, and the quality of life benefits help bypass physician conservatism and drive patient demand. These factors have led analysts from Leerink and Bernstein to forecast peak sales of $1.5-2bn, considerably higher than consensus.
|Selected chronic heart failure drugs|
|Product||Company/ies||Mechanism||2024e indication sales ($m)||Status|
|Entresto||Novartis||Angiotensin II receptor blocker and a neprilysin inhibitor||3,735||Marketed|
|Revascor (MPC-150-IM/rexlemestrocel-L)||Mesoblast||Mesenchymal stem cell therapy||586||Phase III|
|Vericiguat||Bayer/Merck & Co||Guanylate cyclase receptor agonist||444||Phase III|
Akero’s bash at Nash
Nash has been tarred by clinical setbacks, but this has not stopped companies looking at new targets, and Akero is one such contender. The company’s AKR-001 belongs to the fibroblast growth factor class, which is said to regulate lipid and energy metabolism. Non-invasive MRI results from a phase II trial are expected in the first quarter, with full biopsy data expected in the second.
AKR-001 is an analogue of FGF21 and the phase II Balanced study is testing weekly subcutaneous doses versus placebo for up to 16 weeks. 28mg, 50mg and 70mg are being tested, and the primary endpoint is change from baseline in liver fat content measured by MRI-PDFF at week 12. Secondary measures include biomarkers of liver injury and fibrosis.
The study initially recruited 80 patients with stage 1-3 fibrosis in December. This week the company said it had added 30 more subjects, with stage 4 fibrosis, who will be given 50mg AKR-001 or placebo for 16 weeks.
Akero licensed AKR-001 from Amgen in June 2018 for $5m up front after Amgen performed two phase I trials in type 2 diabetes. AKR-001, then known as AMG 876, showed some activity on lipoprotein reduction and insulin sensitivity, an indicator for studies in Nash, though there were no liver-specific endpoints in the studies.
Despite AKR-001 being Akero’s only clinical candidate the group managed to raise $106m in its IPO last year, among the top 20 of 2019. Two other companies with FGF candidates in Nash also floated last year: 89bio raised $98m and NGM Biopharmaceuticals $107m. The latter’s NGM282 has shown 60% fat reduction at the higher dose, but at the cost of a big jump in LDL, and biopsy data are due in the current quarter.
|Clinical-stage fibroblast growth factors for Nash|
|Project||Company||Mechanism of action||Dosing||Upcoming data?|
|AKR-001||Akero/Amgen||FGF21 stimulant||Once weekly||NCT03976401 Q1/Q2|
|Pegbelfermin/BMS-986036||Bristol-Myers Squibb/Ambrx||FGF21 stimulant||Once daily/once weekly||Falcon 1 NCT03486899 and Falcon 2 NCT03486912 H1 20|
|NGM282/aldafermin||NGM||FGF19 regulator||Once daily||Cohort 4 biopsy data Q1 NCT02443116, Alpine due end of 2020 NCT03912532|
|BIO89-100||89bio||FGF21 stimulant||Once weekly/every two weeks||NCT04048135 H2 2020|
|MK-3655/NGM313||Merck & Co/NGM||FGFR1c antibody||Once monthly||Phase II planned|
|Sources: EvaluatePharma, clinicaltrials.gov & company releases.|