This week on Pipeline Moves, we look into the announcements of positive data from two Phase III trials in breast cancer and rare blood disorder, followed by positive topline results from a Phase III trial in ophthalmology. We continue by investigating a suspension and a termination of two Phase II trials, and a completion of a Phase I oncology basket trial.
AstraZeneca announces positive Phase III data in breast cancer
AstraZeneca’s capivasertib saw its Likelihood of Approval (LoA) in metastatic breast cancer leap by 20 points to 71% after the company announced positive Phase III data.
AstraZeneca shared Phase III results in a 26 October press announcement, with GlobalData evaluating the therapy on 31 October. LoA is the probability of a drug receiving market authorization. It is identified via GlobalData’s analysis using a combination of machine learning and its proprietary algorithm, considering characteristics like therapy area, indication and molecule type.
The CAPItello-291 Phase III trial (NCT04305496) tested a combination of capivasertib with Faslodex (fulvestrant) in subjects with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-low or negative locally advanced or metastatic breast cancer after recurrence or progression on or following endocrine therapy. Capivasertib was compared with a combination featuring placebo and Faslodex.
The 708-patient trial achieved both of its primary endpoints, based on the press release. This included a statistically significant improvement in progression-free survival (PFS ) of the overall patient population. The PFS also improved in a biomarker patient subgroup, which had tumours with alterations in the PIK3CA, AKT1 or PTEN genes. While the overall survival (OS) data was not mature at the time of the press release, the company states that the early data is encouraging.
The company announced it plans to present the data at an upcoming medical meeting. Capivasertib is an adenosine triphosphate (ATP)-competitive inhibitor of AKT isoforms 1, 2 and 3.
Positive data in Novartis’s Phase III blood disorder trial
Novartis’s iptacopan saw its LoA in paroxysmal nocturnal haemoglobinuria (PNH) spike by 10 points to 57% after the company announced positive Phase III data. Novartis released Phase III results in a 24 October press announcement, and GlobalData appraised the asset on 26 October.
The Phase III APPLY-PNH study (NCT04558918) achieved its two primary endpoints, showing statistically significant results that demonstrated iptacopan’s superiority over Soliris (eculizumab) and Ultomiris (ravulizumab), both manufactured by Alexion Pharmaceuticals, a part of AstraZeneca, based on the company’s press release. Soliris and Ultomiris are both anti-C5 inhibitors, while iptacopan serves as a complement factor B inhibitor.
According to the release, the twice-daily 200mg iptacopan dose resulted in a clinically meaningful increase in the proportion of patients achieving haemoglobin-level increases of 2 g/dl or more without the need for transfusions after 24 weeks. The factor B inhibitor also demonstrated a significant increase in the proportion of patients achieving 12 g/dl or higher haemoglobin levels without the need for transfusions at week 24.
The treatment was well tolerated, the press release states. The Phase III data will be included in the treatment’s global regulatory submissions in the coming year.
Roche’s positive topline Phase III data in ophthalmology
Roche’s Vabysmo (faricimab) saw its LoA rise in three ophthalmology indications after announcing positive topline results from a Phase III trial. The LoA increased by seven points to 52% in macular oedema and by eight points to 26% in branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). GlobalData evaluated the asset on 28 October after the company issued a press release the day before.
The randomized and double-masked trial (NCT04740905) recruited 553 patients with branch retinal vein occlusion. The study evaluated the safety and efficacy of Vabysmo compared to Regeneron Pharmaceuticals’ Eylea (aflibercept). The primary endpoint measured change from baseline in Best-Corrected Visual Acuity (BCVA) at week 24.
Vabysmo achieved non-inferiority to the control arm and showed rapid drying of retinal fluid, according to the press release. The drug was also investigated in another Phase III trial (NCT04740931) which enrolled 729 people with central retinal or hemiretinal vein occlusion. Roche announced it will present full details of the results at an upcoming medical meeting as it prepares to submit the data to global regulatory authorities.
Vabysmo is a bi-specific antibody and acts as a vascular endothelial growth factor A (VEGF-A) and angiopoietin 2 (Ang-2) inhibitor. It received FDA approval for wet age-related macular degeneration and diabetic macular oedema in January 2022.
Suspension of Phase II multiple sclerosis trial
Emerald Health Pharmaceuticals’s EHP-101 saw its Phase Transition Success Rate (PTSR) plummet in relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS) following the suspension of a Phase II trial in relapsing forms of multiple sclerosis (MS ). The PTSR dropped by 16 points to 17% in RRMS and by 29 points to 22% in SPMS.
The trial status was updated on ClinicalTrials.gov from recruiting to suspended on 21 October, with GlobalData evaluating the asset on 25 October. According to its ClinicalTrials.gov listing, the study was suspended due to a temporary recruitment pause to re-assess the protocol design, particularly the eligibility criteria. PTSR is the probability, given as a percentage, of a drug progressing successfully from one development stage to the next.
The open-label Phase II study (NCT04909502) evaluated the safety, tolerability and preliminary efficacy of EHP-101 in 50 adult patients with relapsing forms of MS. The trial assessed the effects of two doses (25mg and 50mg) of EHP-101 in two treatment arms.
The study’s primary endpoint measured the incidence and severity of treatment emergent adverse events (TEAEs) up to 24 weeks following treatment. The trial’s multiple secondary endpoints measured brain lesion activity, disease progression, disability status and time to first relapse among others.
EHP-101 is an oral formulation of an aminoquinone synthetic derivative of cannabidiol (CBD), which acts by targeting peroxisome proliferator-activated gamma receptors and cannabinoid 2 receptors to elicit a neuroprotective activity.
Phase II in head and neck cancer terminates
MacroGenics’s tebotelimab saw its PTSR in recurrent head and neck cancer squamous cell carcinoma tank 10 points to 4% following a Phase II trial termination. ClinicalTrials.gov updated the trial listing from recruiting to terminated on 17 October, and the PTSR change took effect the next day.
The Phase II trial (NCT04634825) was terminated based on an internal review of safety data, as per the trial listing. The open-label study tested MacroGenics ’s enoblituzumab with tebotelimab or with Incyte’s Zynyz (retifanlimab) in 62 patients with head and neck cancer. Prior to the termination, the trial was anticipated to enrol 82 patients.
The Phase II study’s coprimary endpoints were overall response rate (ORR) of both treatment groups and the incidence of adverse events. Tebotelimab is an immune checkpoint inhibitor targeting lymphocyte activation gene 3 protein (LAG3) and programmed cell death protein 1 (PD1). Both Zynyz and enoblituzumab are also immune checkpoint inhibitors.
Completion of Phase I oncology basket study
Eisai’s E-7766 saw its PTSR rise by seven points in five oncology indications after completing a Phase I clinical trial. E-7766’s PTSR settled at 61% in colorectal cancer and melanomas, 57% in lymphoma, 63% in head and neck cancer squamous cell carcinoma, and 39% in solid tumour.
The study’s ClinicalTrials.gov listing was updated from recruiting to completed on 21 October with GlobalData evaluating the PTSR on 25 October.
The open-label, multicentre Phase I/Ib trial (NCT04144140) studied the safety, tolerability, and preliminary clinical activity of E-7766 as a single agent administered intratumorally in participants with advanced solid tumours or lymphomas.
The study initially planned to enrol 120 people, but the actual study was only able to enrol 24 participants. All of the primary endpoints were related to participants’ clinical responses to the dose escalation part of the study as well as toxicity and adverse events.
E-7766 is an innovative drug that acts as an activator of the stimulator of interferon genes protein (STING protein). This results in an effector T cell response with a lower inflammatory signature in the immune system, thereby promoting an anti-tumour effect.