Pipeline metastasis: Prospects drop after ovarian cancer phase III trial fails

this week in Pipeline movement, we first looked at two phase III trials in oncology and kidney disease that failed to meet their endpoints. Happily, we investigated completion status in vitiligo, solid tumors, hepatitis B, and familial amyloid cardiomyopathy.

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Phase III trial terminated

The likelihood of approval (LoA) for Aravive’s batiraxcept in ovarian cancer has dropped sharply after a Phase III trial was terminated.

The drug’s LoA for ovarian cancer dropped 10 percentage points to 1%. LoAs are identified through analysis by GlobalData using a combination of machine learning and proprietary algorithms. The LoA of a drug can be calculated by considering characteristics such as therapeutic area, indication, and molecule type.

On October 26, the trial’s status on ClinicalTrials.gov was updated from active, not recruiting to terminated. According to the website, the reason for the termination was that the trial showed no significant difference in median progression-free survival (PFS) between the baticept and paclitaxel or paclitaxel alone groups.

The company added that this did not compromise overall survival and no new safety signals were identified. GlobalData valued the asset on October 31.

A randomized, double-blind phase III trial (NCT04729608) compared the efficacy and safety of batecept plus paclitaxel versus placebo plus paclitaxel in patients with platinum-resistant recurrent ovarian cancer.

Batiraxcept works by inhibiting growth arrest-specific protein 6 (GAS6). When the AXL receptor binds to the GAS6 ligand on tumor cells, the AXL receptor is activated, leading to tumor cell proliferation. The drug candidate blocks this binding and prevents tumor progression.

Phase III trial failed

Travere Therapeutics’ LoA for Filspari (sparsentan) fell after a Phase III trial in focal segmental glomerulosclerosis (FSGS) failed to meet the endpoint. Filspari’s LoA dropped by 9 percentage points, from 23% to 14%.

published in” New England Journal of Medicine noted that among patients with FSGS, there were no significant between-group differences in eGFR slope at 108 weeks, although the reduction in proteinuria was greater in the Filspari group than in the irbesartan group. GlobalData evaluated the asset on November 6.

A phase III trial (NCT03493685) is investigating the long-term renal protective potential of Filspari compared with the angiotensin receptor blocker irbesartan in patients with primary and hereditary FSGS.

Filspari is a selective dual-action receptor antagonist with affinity for endothelin (type A) and angiotensin II receptors (type 1). Endothelin and angiotensin II are vasoconstrictor substances that can also exert proliferative and proinflammatory effects.

Filspari was originally developed by Bristol Myers Squibb and later licensed to Pharmacopeia, which was acquired by Ligand Pharmaceuticals. Travere acquired the drug from Ligand in 2012.

Phase Ib trial completed

VYNE Therapeutics’ VYN201’s phase conversion efficacy rate (PTSR) increased in vitiligo after announcing positive data from a Phase Ib trial. The drug’s PTSR increased 14 percentage points to 79%. PTSR is the probability (expressed as a percentage) that a drug successfully progresses from one development stage to the next.

On October 30, the company announced positive clinical data from the Phase Ib trial in a press release. The trial investigated the safety, tolerability and pharmacokinetics of three different doses of once-daily topical VYN201 in 29 subjects. Specifically, the study tested doses of VYN201 at 0.5%, 1% and 2%.

The trial measured the treatment’s potential efficacy and impact on skin depigmentation and repigmentation progression via the Facial Vitiligo Area Score Index (F-VASI).

According to an Oct. 30 press release, significant clinical improvement was observed in the 1% and 2% cohorts with dose-dependent responses. Specifically, 50% of subjects in the 1% cohort had an improvement in F-VASI score equal to or greater than 25%. The treatment was generally well tolerated, with no serious adverse events reported.

VYN-01, a topically administered pan-bromodomain BET inhibitor, has so far shown reductions in pro-inflammatory and disease-associated biomarkers, according to an Oct. 30 press release.

The company currently plans to advance the asset into a Phase IIb study in the first half of 2024, according to a press release.

Moderna Phase 1 trial completed

Moderna’s MEDI1191 showed increased PTSR in solid tumors following completion of Phase I trial. The drug’s PTSR improved by 12 points to 49%.

On October 31, the status of the Phase I trial (NCT03946800) was updated from active, not recruiting to completed on ClinicalTrials.gov, and GlobalData evaluated the asset the next day.

The open-label, dose-escalation and expansion study evaluated MEDI1191 in combination with AstraZeneca’s Imfinzi (durvalumab) in adult patients with advanced solid tumors. The study enrolled 61 patients.

This gene therapy acts as an IL-12 activator and is currently being developed to treat solid tumors.

Hepatitis B Phase I Trial Completed

Drug Farm’s DF-006 showed an increase in hepatitis B PTSR following completion of Phase I trial. The drug’s PTSR increased 6 percentage points to 58%.

On 27 October, the status of the Phase I trial (ACTRN12621000592842) in the Australian and New Zealand Clinical Trials Registry was updated to Complete, and GlobalData assessed the asset on 1 November. The purpose of this placebo-controlled study is to evaluate the safety, tolerability and pharmacokinetics of DF-006.

DF-006 is an alpha-protein kinase 1 inhibitor (ALPK1) activator developed by Drug Farm, which has offices in the United States and China. This small molecule drug candidate is being developed to treat hepatitis B virus (HBV) infection and hepatocellular carcinoma.

Cardiology trial completed

Alexion Pharmaceuticals’ ALXN-2220 showed an increase in PTSR for the treatment of familial amyloid cardiomyopathy (ATTR-CM) following completion of a Phase I trial. The drug’s PTSR improved by 7 points to 80%.

The Phase I trial (NCT04360434) status was updated on ClinicalTrials.gov from active, not recruiting to completed on November 3, and GlobalData evaluated the asset on November 6.

This randomized, placebo-controlled, double-blind, dose-escalation study evaluated ALXN-2220 in patients with amyloid transthyretin cardiomyopathy. The study enrolled 46 patients.

ALXN-2220 works by inhibiting the transthyretin (TTR) protein and is being developed to treat ATTR-CM.

Read the latest version:

Pipeline changes: Progress prospects for hearing loss drug dwindle after trial halted

need to know:

GlobalData’s proprietary model uses a combination of machine learning and algorithms to calculate PTSR and LoA for individual drugs. The LoA provides the probability that the drug will ultimately receive market authorization, while the PTSR indicates the probability that the drug will advance to the next phase of clinical development. The model uses data points from individual drugs, clinical trials, regulatory milestones, corporate and financial databases.