Other urology pipeline-related news includes published data from a randomized controlled trial of a complicated urinary tract infection agent as well as level 1 evidence of partial gland ablation for prostate cancer.
First patients treated in phase II study of hyperoxaluria agent
Allena Pharmaceuticals, Inc. announced the treatment of the first patients in Study 206, an open-label phase II basket study evaluating ALLN-177 in adults and adolescents with primary hyperoxaluria, or enteric hyperoxaluria with advanced chronic kidney disease and elevated plasma oxalate. ALLN-177 is a first-in-class, non-absorbed, orally administered enzyme that is designed to degrade oxalate within the gastrointestinal tract to treat severe hyperoxaluria. Study 206 is a multicenter, open-label, single-arm study that will enroll between 15 and 20 patients in the U.S. and Europe aged 12 years and older who will be treated with ALLN-177 for 12 consecutive weeks. Subjects will self-administer 7,500 units of ALLN-177 with each meal or snack five times per day. Study endpoints are change from baseline in 24-hour urinary oxalate excretion and plasma oxalate levels. Patients with kidney failure or on dialysis may comprise up to 25% of total enrollment.
Data published from randomized controlled trial of cUTI agent
The Lancet Infectious Diseases has published clinical results from the pivotal randomized controlled trial evaluating cefiderocol for the treatment of complicated urinary tract infection (cUTI) in patients at risk of multidrug-resistant gram-negative infections (Lancet Infect Dis Oct. 25, 2018 [Epub ahead of print]). Results from the study demonstrated treatment with cefiderocol met non-inferiority versus imipenem/cilastatin (IPM/CS) in patients with cUTI at test of cure (TOC), according to Shionogi & Co., Ltd. In the study, 73% (183/252) of patients in the cefiderocol group met the primary endpoint (combination of clinical response and microbiological response at TOC) versus 55% (65/119) in the IPM/CS group, with an adjusted treatment difference of 18.58%. These results in a post-hoc analysis showed that cefiderocol was superior to IPM/CS.
Pivotal trial to evaluate oral agent for polycystic kidney disease
Sanofi is beginning a pivotal clinical trial to study the safety, efficacy, and tolerability of an investigational oral agent called venglustat for certain patients with autosomal dominant polycystic kidney disease (ADPKD). The international trial is enrolling patients who are at risk of rapidly progressive ADPKD. Venglustat is an investigational oral therapy designed to inhibit the abnormal accumulation of glucosylceramide (GL-1), which plays a role in production of glycosphingolipids. In genetic mouse models of ADPKD, inhibition of glycosphingolipid production has been shown to reduce kidney cyst growth (Nat Med 2010; 16:788-92). The clinical significance of this is under investigation, according to Sanofi. Venglustat has received Orphan Drug designation in the U.S. for the treatment of ADPKD. The ADPKD clinical trial will be conducted at sites in the U.S., Canada, China, Japan, and several European Union countries.
Cancer subtyping platform may provide bladder Ca biomarkers
GeneCentric Therapeutics presented the first data on the application of its proprietary Cancer Subtyping Platform to bladder cancer and its potential utility to provide drug response biomarkers for the disease. The studies, conducted by GeneCentric scientists in collaboration with researchers at the University of North Carolina Chapel Hill’s Lineberger Cancer Center, assigned four gene expression subtypes based on approximately 2,700 genes from 408 bladder cancer patients in The Cancer Genome Atlas. The researchers then developed a subtype signature based on 60 genes and tested the 60-gene set in two additional data sets. Analysis of the gene signatures suggested additional study of their potential as therapeutic biomarkers independently as well as in combination with other molecular features, according to GeneCentric Therapeutics. For example, subtypes showed differences in the expression profiles of genes that are promising therapeutic targets in bladder cancer, such as FGFR3 and ERBB2. The differences were consistent across multiple data sets. Bladder cancer subtypes also showed variability in immune profiles that is likely to inform the response to immunotherapy. Subtypes were also found to be significantly prognostic for Stage 2 and 3 bladder cancer. The data were presented at the American Society of Clinical Oncology annual meeting in Chicago.
Next: New studies evaluate device’s efficacy in preserving penile lengthNew studies evaluate device’s efficacy in preserving penile length
The Mayo Clinic has initiated two new trials evaluating the efficacy of a new penile traction therapy device (RestoreX) in preserving or improving penile length. The first study is a randomized, controlled trial of 60 men post-prostatectomy who will be assigned to control or one of two treatment arms (traction 30 min. daily x 5 days/week vs. 60 min. daily x 7 days/week). Treatment is initiated at 1 month after prostatectomy and continues until 6 months post-op. All men then enter an open-label phase for 3 months. Primary outcomes are penile length, and secondary outcomes include assessments of sexual function, urinary outcomes, development of Peyronie’s disease, and adverse events. The second study is an open-label trial of 40 men undergoing placement of a penile prosthesis. Men will be offered the option of utilizing traction with RestoreX for 90 minutes daily for 3 months prior to the penile prosthesis or proceed directly with surgery. Primary outcomes include stretched penile length pre- and post-treatment and the size of prosthesis inserted between those using traction versus no traction. Secondary outcomes include subjective measures of satisfaction, compliance, and adverse events. Groupings will be matched on baseline penile length to limit confounders. RestoreX is currently used for the treatment of Peyronie’s disease.
Cell therapy yields significant improvement in erectile function
Phase I results from a trial of adipose-derived regenerative cells (ARDCs, Cytori Cell Therapy) in erectile dysfunction following radical prostatectomy were recently published in Urology (June 27, 2018 [Epub ahead of print]). In the trial, 21 patients with ED after radical prostatectomy, with no signs of recovery following conventional therapy, received a single intracavernous injection of autologous ADRCs. Six men were incontinent and 15 were continent at inclusion. At 12 months following treatment, erectile function assessed using the International Index of Erectile Function-5 showed a statistically significant improvement from a median baseline score of 6 to a median of 8; p=.004. Although median Erection Hardness Score (EHS) was unchanged in the entire cohort, patients in the continent subset exhibited statistically significant improvement in EHS from a baseline median score of 1 to a median of 2 at 12 months; p=.03.
Level 1 evidence of partial gland ablation for PCa published
The Journal of Urology has published 4-year follow-up data of the landmark phase III PCM301 trial of padeliporfin di-potassium (TOOKAD), a novel treatment for localized, low-risk prostate cancer (J Urol June 2, 2018 [Epub ahead of print]). Publication of this study provides the longest reported Level 1 evidence of safety and efficacy of partial gland ablation for early-stage prostate cancer to date, Steba Biotech said. Analysis of 4-year follow-up of PCM301 demonstrated that vascular targeted photodynamic therapy (VTP) mediated by padeliporfin di-potassium significantly reduced the subsequent finding of higher grade cancer on biopsy and, consequently, significantly fewer patients converted to radical therapy. The rate of conversion to radical therapy after padeliporfin di-potassium VTP compared with active surveillance at 2 years (7% vs. 32%) was maintained at 3 (15% vs. 44%) and 4 years (24% vs. 53%) (HR: 0.31, 95% CI: 0.21-0.46; p<.001).
Breakthrough designation granted for metastatic CRPC agent
The FDA has granted Breakthrough Therapy designation for rucaparib (Rubraca) as a monotherapy treatment of adult patients with BRCA1/2-mutated metastatic castration-resistant prostate cancer who have received at least one prior androgen receptor-directed therapy and taxane-based chemotherapy. The designation was based on initial efficacy and safety results from TRITON2, the phase II study of rucaparib in men with advanced prostate cancer with BRCA 1/2 mutations (germline or somatic) and deleterious mutations of other homologous recombination repair genes, in the metastatic castration-resistant setting. Developer Clovis Oncology, Inc. said initial data from the TRITON2 clinical study will be presented for the first time at the European Society for Medical Oncology annual congress in Munich.
Next: Drug combo shows positive phase III results in advanced RCCDrug combo shows positive phase III results in advanced RCC
Merck KGaA and Pfizer Inc. reported positive top-line results from the pivotal phase III JAVELIN Renal 101 study evaluating avelumab (BAVENCIO) in combination with axitinib (INLYTA) compared with sunitinib (SUTENT) as initial therapy for patients with advanced renal cell carcinoma. As part of a planned interim analysis, an independent Data Monitoring Committee confirmed that the trial showed a statistically significant improvement in progression-free survival (PFS) by central review for patients treated with the combination whose tumors had PD-L1+ expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective). According to the statistical analysis plan, if PFS was statistically significant in the PD-L1+ subgroup, then PFS in the entire study population was to be analyzed for statistical significance. JAVELIN Renal 101 will continue as planned to the final analysis for the other primary endpoint of overall survival. Merck and Pfizer intend to pursue a regulatory submission in the U.S. based on these interim results, and these results will be discussed with global health authorities. A detailed analysis will also be submitted for presentation at an upcoming medical congress.
New Drug Application submitted for urothelial cancer agent
The Janssen Pharmaceutical Cos. of Johnson & Johnson announced that a New Drug Application has been submitted to the FDA seeking approval of erdafitinib for the treatment of patients with locally advanced or metastatic urothelial cancer and certain fibroblast growth factor receptor (FGFR) genetic alterations whose tumors have progressed after prior chemotherapy. Erdafitinib is an investigational, once-daily, oral pan-FGFR inhibitor that received Breakthrough Therapy Designation from the FDA in March 2018. The NDA submission is based on data from the BLC2001 (NCT02365597) phase II clinical trial, which evaluated the efficacy and safety of erdafitinib in the treatment of adult patients with locally advanced or metastatic urothelial cancer, whose tumors have certain FGFR alterations. The primary endpoint was the percentage of participants with objective response, defined as complete response or partial response based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria.
Stricture device receives financing, FDA approval of U.S. study
Urotronic has raised $20 million in a strategic round led by HM (Hillhouse & Mayo Clinic) Ventures to support the growth of the Optilume drug-coated balloon, a two-pronged approach to treatment of urethral stricture. In clinical trials performed both in Latin America and the United States, Optilume has performed as intended in both opening blockages and inhibiting the formation of scar tissue that can develop quickly after any medical intervention. The procedure can be performed in an outpatient setting. Urotronic also announced that it has received FDA approval to begin its second U.S. study of Optilume. The latest U.S. Investigational Device Exemption Pivotal clinical study, titled ROBUST III, will enroll up to 200 men from 20 clinical sites across the U.S. and will start immediately. The first FDA-approved U.S. trial of the Optilume for an Early Feasibility Study began in November 2017 and is currently underway in five medical centers around the country.
Drug developer licenses novel gene therapy for overactive bladder
Urovant Sciences has licensed a novel investigational gene therapy for patients with overactive bladder symptoms who have failed oral pharmacologic therapy. Urovant has licensed global rights for the development and commercialization of hMaxi-K from Ion Channel Innovations. There are no currently available FDA-approved gene therapy treatments for overactive bladder, according to Urovant. hMaxi-K has been evaluated in two phase I studies in OAB patients, including a small, double-blind, placebo-controlled phase Ib clinical trial as an intravesical injection in women with overactive bladder symptoms. Ion Channel Innovations completed the phase Ib study in 2017 and found hMaxi-K to be generally well tolerated. Clinical results of the trial, which included a limited number of patients (n=13), indicated dose-dependent improvements in urinary urgency and frequency, achieving statistical significance (p<.05) in the high-dose cohort.
Government funding awarded for investigational IC/BPS agent
Alivio Therapeutics, an affiliate of PureTech Health plc, announced a $3.3 million U.S. Department of Defense Technology/Therapeutic Development Award to advance Alivio’s product candidate, ALV-107, for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS) with Hunner’s lesions. The funds will support Alivio’s preclinical research and development activities, including GMP manufacturing, to enable the filing of an investigational New Drug Application for ALV-107. Alivio’s platform technology has demonstrated proof-of-concept in 10 different preclinical models of inflammation, including a validated preclinical model for the treatment of IC/BPS. ALV-107 showed durable pain control throughout a 24-hour study period in this model of IC/BPS, lasting at least 12 times longer than lidocaine at a comparable dose (ALV-107, 16 mg/kg; conventional lidocaine, 16 mg/kg).