Clinical Catch-Up: December 16-20
Heading into the holidays, there was still plenty of clinical trial news last week. Here’s a look.
Novartis announced that its LUSTER-1 and LUSTER-2 Phase III trials of fevipiprant for asthma failed to meet their clinically relevant endpoints. As a result, the company indicated it is halting the developing of the drug for asthma. Fevipiprant is a novel, steroid-free once daily pill that blocks the DP2 pathway, which regulates the inflammatory cascade in asthma. The primary endpoint of both studies was the decrease of the annual rate of moderate-to-severe exacerbations for a year.
Cellectar Biosciences announced summary data from 20 patients receiving a single dose of CLR 131 in its Phase II CLOVER-1 trial in select relapsed/refractory B-cell malignancies. Data showed a 30% overall response rate (ORR), a 75% clinical benefit rate, and an average progression free survival (PFS) of 4.5 months. CLR 131 is a small molecule radiotherapeutic Phospholipid Drug Conjugate (PDC) designed to deliver cytotoxic radiation directly and selectively to cancer cells.
Kamada announced its first patient had been randomized in Europe into its Phase III InnovAATe trial. The trial is studying the company’s inhaled Alpha-1 Antitrypsin (AAT) therapy for Alpha-1 Antitrypsin Deficiency (AATD). Earlier studies have shown that AAT slowed FEV1 decline and seems to reduce lung inflammation and destruction.
Alnylam Pharmaceuticals announced positive results from its ILLUMINATE-A Phase III trial. The study was investigating lumasiran, an RNAi therapeutic that targets glycolate oxidase (GO) for the treatment of primary hyperoxaluria type 1 (PH1). The trial met its primary efficacy endpoint and all tested secondary endpoints. The primary efficacy endpoint was percent change from baseline, compared to placebo, in 24-hour urinary oxalate excretion averaged across months three to six.
GlaxoSmithKline announced results from its pivotal DREAMM-2 Phase III trial of belantamab mafodotin in multiple myeloma (MM). In the GSK trial, belantamab mafodotin showed a clinically meaningful overall response rate (ORR) of 31% with the 2.5 mg/kg dose in patients with heavily pre-treated MM. Of the 97 patients in the 2.5 mg/kg cohort, 31% achieved an overall response. Of that subgroup, 18 hit a very good partial response or better, with three patients with stringent complete or complete responses. Overall survival in patients achieving a response had not yet reached the mark at the six-month follow-up period.
Vermillion enrolled the first patient in its study that compares OVA1 to CA125 assay for detection of ovarian cancer risk in African American women. The trial will enroll over 200 prospective African American women with adnexal masses.
INmuneBio completed the Phase I trial of INB03 and the database has been locked. The trial was a dose-escalation trial in patients with advanced solid tumors. They identified 1 mg/kg as the recommended dose for Phase II studies. INB03 is part of the company’s DN-TNF product platform that uses dominant-negative technology to selectively neutralize soluble TNF, a driver of innate immune dysfunction. In the Phase II trial, it will target trastuzumab resistant HER2+ breast cancer using INB03 as part of combination therapy.
Avadel Pharmaceuticals completed enrollment in the REST-ON Phase III trial of FT218. FT218 is a once-nightly formulation of sodium oxybate for treating excessive daytime sleepiness and cataplexy in narcolepsy patients. The REST-ON study has enrolled a total of 212 patients. Topline results are expected in the second quarter of 2020.
Alkahest initiated a Phase II trial of AKST4290 in age-related macular degeneration (AMD). AKST4290 is an oral small molecule CCR3 inhibitor. The study is evaluated the drug on choroidal blood flow (ChBF) in that patient population.
Biohaven Pharmaceutical announced positive topline data from its Phase II/III trial of intranasal vazegepant to treat migraine. The 10 and 20 mg doses of vazegepant were statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from most bothersome symptoms at two hours using a single dose. Vazegepant is part of the company’s NOJECTION Migraine Platform.
Proteostasis Therapeutics announced positive topline results from its Phase II trial of its proprietary cystic fibrosis transmembrane conductance regulator (CFTR) modulator combinations in F508del homozygous and heterozygous CF patients 18 years of age and older. The trial is evaluating the efficacy, safety and tolerability of the company’s once-daily combinations of dirocaftor and posenacaftor with or without nesolicaftor over four weeks of treatment.
Flexion Therapeutics enrolled the first three patients in its trial of Zilretta in patients with either osteoarthritis of the shoulder or frozen shoulder, also called adhesive capsulitis. The Phase II trial is expected to enroll up to 250 patients. Zilretta is triamcinolone acetonide extended-release injectable suspension which is approved for intra-articular injection for osteoarthritis pain of the knee.
Bellerophon Therapeutics announced positive topline data from Cohort 2 of its ongoing Phase II/III trial of INOpulse for Pulmonary Hypertension associated with Interstitial Lung Disease (PH-ILD). Those receiving the drug showed statistically significant improvement in moderate to vigorous physical activity. There were also benefits in actigraphy parameters and patient reported outcomes. INOpulse is a proprietary pulsatile nitric oxide delivery system.
Acer Therapeutics announced full enrollment of Part B of its pivotal trial of ACER-001 (sodium phenylbutyrate) for Urea Cycle Disorders (UCDs). Part A evaluated bioavailability of three different oral suspension formulations of ACER-001 compared to Buphenyl in 20 health adults. Part B is a single-center, single-blind, randomized, single-dose crossover study to show bioequivalence of ACER-001 compared to Buphenyl in 36 healthy adults.
BeiGene announced results from its Phase III ASPEN trial comparing Brukinsa (zanubrutinib) to ibrutinib for Waldenstrom’s macroglobulinemia (WM). Both drugs are BTK inhibitors. The trial did not meet statistical significance on its primary endpoint of superiority in complete response and very good partial response rates.
Arcutis Biotherapeutics announced topline results from its Phase III study of ARQ-151 in atopic dermatitis. ARQ-151 is a once-a-day topical cream formulation of roflumilast, a Phosphodiesterase type 4 inhibitor. The primary endpoint was mean reduction in the Eczema Area and Severity Index (EASI) Total Score after 4 weeks of once-daily treatment. Neither dose reached statistical significance compared to vehicle.
Adamas Pharmaceuticals reported that its Phase III INROADS trial of Gocovri (ADS-5102) for multiple sclerosis (MS) with walking impairment met its primary endpoint. Gocovri was approved by the FDA for the treatment of dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy. It is not approved for MS with walking impairment.
The primary endpoint of the study was a 20% improvement in walking speed from baseline to 12 weeks post-treatment. This was measured by the Timed 25 Foot Walk. The patients taking 274 mg of the drug had a statistically significant improvement in response rate of 21.1% compared to 11.3% in patients taking the placebo. At a lower dose of 137 mg, the response was 17.6%.
However, key secondary endpoints included mean change in the Timed 25-Foot Walk, the Timed Up and Go, and the 2-Minute Walk at 12-week post-treatment at both doses. The drug did not show a significant effect on any of those measures at either dose.
Eli Lilly launched the first, long-term, real-world evidence trial of Emgality (galcanezumab-gnlm) to evaluate the real-world effectiveness of Emgality in comparison to other migraine prevention treatments. It plans to enroll about 2,850 patients across the U.S., Europe and Asia. It will track prescribing and treatment choices related to migraine preventive treatments over a two-year period.
Chondrial Therapeutics dosed the first patients in its Phase I trial of single ascending doses of CTI-1601. CTI-1601 is a recombinant fusion protein designed to deliver human frataxin to patients with Friedreich’s ataxia (FA). The trial will enroll adults over the age of 18 with FA.
Zogenix published data from its Phase III trial, Study 1, of Fintepla (fenfluramine oral solution) in children and young adults with Dravet syndrome. Dravet syndrome is a rare, severe infantile-onset epilepsy marked by frequent, disabling seizures that don’t respond well to anti-epileptic drugs. The study showed both doses added to existing treatments offered a significant decrease in convulsive seizure frequency compared to placebo.
Homology Medicines announced promising initial clinical data from its gene therapy clinical trial in phenylketonuria (PKU). The pheNIX trial is a Phase I/II trial. As of December 2, two patients had received HMI-102 gene therapy in the low-dose Cohort 1 and one patient in mid-dose Cohort 2.
Angion Biomedica dosed the first patient in a Phase I trial of ANG-3070 in healthy volunteers. The drug is an oral small molecule to treat idiopathic pulmonary fibrosis, primary focal segmental glomerulosclerosis (FSGS) and other fibrotic diseases. It is a fibrokinase inhibitor.
Mycovia Pharmaceuticals completed enrollment for its ongoing Phase III ultraVIOLET clinical trial of VT-1161 for recurrent vulvovaginal candidiasis (RVVC). The trial was initiated in February 2019 to evaluate the safety and efficacy of the drug and its ability to treat acute episodes of vulvovaginal candidiasis in women with RVC compared to fluconazole.
Minerva Neurosciences' Phase IIb trial of MIN-117 in adults with moderate to severe major depressive disorder (MDD) who also presented with symptoms of anxious distress failed to meet its primary and key secondary endpoints. Neither dose of the drug demonstrated a statistically significant separation from placebo on symptoms of MDD over six weeks or in the key secondary endpoint, anxiety.
Rezolute announced topline data from its Phase I trial of AB101 in type 1 and type 2 diabetes. AB101 is an ultra-long acting basal insulin. The drug was given subcutaneously in three ascending dosing cohorts in type 2 diabetes, showing slow onset and sustained insulin levels and activity for more than seven days. At higher doses, there was more variability of onset and required greater drug volume than expected. The company thinks it needs more formulation development before advancing further in the clinic.
Stealth Biotherapeutics reported that its Phase III MMPOWER-3 clinical trial of elamipetride failed to meet its primary endpoint. The trial was evaluating the effectiveness of elamipetride in patients with primary mitochondrial myopathy (PMM). The primary endpoints for the MMPOWER-3 trial were changes in the six-minute walk test and Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) Total Fatigue Score. The drug was well tolerated, and most adverse events were mild to moderate.