Catch up on all the notable drug and device approvals in urology over the past year.
From artificial intelligence software to eCoin to avanafil, 2022 was another busy year in the urology space, with multiple drugs and devices receiving FDA approval. In this article, we look back on the notable developments in treatment and diagnostics within the specialty.
The FDA granted 510K clearance to 23andMe’s direct-to-consumer (DTC) genetic health risk report on a hereditary marker for prostate cancer.1 The clearance is specifically for reporting on the HOXB13 G84E mutation. Research has shown that harboring this mutation significantly increases a man’s prostate cancer risk. According to 23andMe, clinical research has shown that 33% to 53% of men harboring the G84E variant will develop prostate cancer, and these men also tend to develop the disease at an earlier age. The prevalence of G84E mutations is highest among men with Northern European ancestry. Of note, the test does not assess for all genetic markers of enhanced prostate cancer and the report is not a substitute for recommended cancer screenings.
The FDA approved FoundationOne CDx for use as a companion diagnostic to identify patients with solid tumors that are microsatellite instability high (MSI-H) and thus eligible to be treated with the immunotherapy pembrolizumab (Keytruda).2 Pembrolizumab was approved by the FDA in 2017 for the treatment of patients with MSI-H or mismatch repair deficient solid tumors. The emergence of such tumor-agnostic approvals has increased the significance of genomic profiling in urology.
The FDA approved the eCoin leadless tibial neurostimulator for the management of urinary urge incontinence (UUI), a condition experienced by more than 60% of patients with overactive bladder (OAB).3 eCoin is a tibial neurostimulator that is the shape and size of a nickel. It is implanted in the lower leg under local anesthetic in an office or outpatient procedure by a urologist or urogynecologist. The procedure takes approximately 20 minutes. The approval was based on results from a pivotal, open-label, single-arm trial that included 133 patients with OAB with UUI. eCoin was a third- or fourth-line OAB therapy for these patients. OAB drugs were not allowed during the trial. eCoin met the primary end point of the study by achieving at least a 50% improvement in UUI in 68% of patients after 48 weeks of treatment.4
The FDA approved Axonics F15, a recharge-free sacral neuromodulation implantable neurostimulator (INS) for the treatment of patients with bladder and bowel dysfunction.5 Axonics, developer of the device, announced the approval in a news release. The Axonics F15 uses a primary cell battery, and at standard stimulation parameters is expected to function for at least 15 years, and at lower energy settings, 20 or more years.The constant current automatically adjusts stimulation output, and it is MRI compatible with 1.5T and 3.0T whole-body scanners. The patient’s remote control is a recharge-free, intuitive fob.
The FDA approved the targeted radioligand therapy 177Lu-PSMA-617 (LuPSMA; lutetium Lu-177 vipivotide tetraxetan; Pluvicto) for the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in the post–androgen receptor pathway inhibition, post–taxane-based chemotherapy setting.6 The approval of LuPSMA is based on findings from the phase 3 VISION trial in which adding LuPSMA to standard of care (SOC) led to a nearly 40% reduction in the risk of death vs SOC alone in patients with progressive PSMA-positive mCRPC.7 The data the FDA reviewed showed that at a median follow-up of 20.9 months, the addition of LuPSMA improved the median overall survival by 4 months over SOC alone (HR, 0.62). LuPSMA also led to a 60% reduction in the risk of disease progression or death (HR, 0.40).7
The FDA approved testosterone undecanoate (Tlando) for the treatment of adult men with hypogonadism, according to Antares Pharma, developer of the oral treatment for testosterone replacement therapy.8 According to the FDA label, the treatment is approved for either primary hypogonadism (congenital or acquired), defined as testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter syndrome, chemotherapy, or toxic damage from alcohol or heavy metals; or hypogonadotropic hypogonadism (congenital or acquired), defined as gonadotropin or luteinizing hormone-releasing hormone deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. The testosterone undecanoate capsule was officially launched in the US hypogonadism market in June 2022.
A ready-to-inject subcutaneous depot formulation of leuprolide mesylate (Camcevi; 42 mg) is now commercially available in the United States for the treatment of patients with advanced prostate cancer.9 The FDA approved the subcutaneous formulation in 2021 based on a phase 3 trial, in which the primary end points were the percentage of subjects with suppression of serum testosterone (≤50 ng/dL) by day 28 and from day 28 to day 336.10 These end points were successfully achieved, as 97% of participants had a serum testosterone level of 50 ng/dL or less by the end of the trial. Further, 95.9% of participants reached a serum testosterone level of 20 ng/dL or less. Of note, following the first injection of leuprolide mesylate subcutaneous injectable suspension at 50 mg, PSA levels significantly declined, and this PSA reduction continued to occur to the end of the study.
The FDA granted 510K clearance to the hyaluronic acid rectal spacer Barrigel for use in patients with prostate cancer receiving radiotherapy. Barrigel is used to separate and increase the distance between the anterior rectal wall and the prostate when the patient is receiving radiotherapy. The intent of the technology is to decrease the amount of radiation received by the rectum, minimizing the potential long-term adverse effects of the treatment. The clearance was based on the Barrigel Prostate Trial, a randomized controlled trial that used the rectal spacer when administering hypofractionated radiotherapy to patients with prostate cancer. “Barrigel is proven superior in the reduction of acute and long-term grade 2 [or greater gastrointestinal] toxicity at 3 and 6 months compared [with] control,” Martin King, MD, PhD, medical director of the Barrigel Prostate Trial, said in a news release.11
The FDA granted clearance to the leva Pelvic Health System for the frontline treatment of women with chronic fecal incontinence. Leva is a small vaginal probe that is implanted and paired with a mobile application. Using the system helps women strengthen their pelvic floor muscles without medication or surgery. The clearance for chronic fecal incontinence follows a prior approved indication for the treatment of women with stress, mixed, and mild to moderate urinary incontinence. “First-line treatment alternatives [for fecal incontinence] have been limited in the past so it’s important that clinicians can now consider leva as a new treatment option that is supported by robust clinical data,” Holly E. Richter, PhD, MD, professor and J. Marion Sims Endowed Chair, in Obstetrics and Gynecology at the University of Alabama at Birmingham, said in a news release.12
The FDA has approved testosterone undecanoate (Kyzatrex), an oral testosterone replacement therapy for the treatment of adult males with conditions associated with hypogonadism.13 The approval was based on results from the multicenter, open-label phase 3 MRS-TU-2019EXT trial (NCT04467697). The study enrolled 155 males with hypogonadism. According to investigators, the primary efficacy end point was the percentage of Kyzatrex-treated patients with mean plasma total testosterone concentration over 24 hours within the normal range of 222 to 800 ng/dL on the final [pharmacokinetic] visit of the study at day 90. The median patient age was 50 years (range, 22-66). In the efficacy population (n=139), 88% of participants (n=122) reached the primary study end point.
The FDA has approved darolutamide (Nubeqa) for use in combination with docetaxel for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC).14 The approval was based on findings from the placebo-controlled phase 3 ARASENS trial (NCT02799602), which showed that adding darolutamide to standard androgen deprivation therapy (ADT) and docetaxel boosted overall survival (OS) vs ADT/docetaxel alone in patients with mHSPC. Results published in the New England Journal of Medicine15 showed that at a median follow-up of 43.7 months for darolutamide plus ADT/docetaxel and 42.4 months with placebo plus ADT/docetaxel, the active therapy resulted in a 32.5% reduction in the risk of death (HR 0.68; 95% CI 0.57-0.80; P<.001). Median OS in the darolutamide arm was not estimable (NE; 95% CI, NE-NE) vs 48.9 months (95% CI, 44.4-NE) with placebo. Rates of OS at 48 months were 62.7% and 50.4%, respectively.
The FDA has granted 510(k) clearance to an artificial intelligence (AI) software program that may enhance the efficiency and accuracy of prostate cancer diagnosis. Through computer-aided detection, ProstatID offers a colorized translucent overlay of 2D axial T2 MRI to identify soft tissue lesions that may warrant closer inspection for potential malignancy. The ProstatID algorithm also utilizes the Prostate Imaging Reporting and Data System to score the cancer probability of suspicious lesions, according to manufacturer Bot Image. The company noted in a news release that results of 2 internal studies showed improved accuracy and a reduced false positive rate with the use of ProstatID.16
The FDA updated the label for mitomycin-containing reverse thermal gel (Jelmyto) in low-grade upper-tract urothelial cancer by extending the in-use period for pyelocalyceal solution admixture from 8 hours to 96 hours (4 days) following reconstitution of the product, according to UroGen, developer of the treatment. “This label change for Jelmyto gives physicians and patients the option to treat in the morning, whereas, in most cases, the afternoon was the only option before the change,” Rian J. Dickstein, MD, chairman of urology at University of Maryland Baltimore Washington Medical Center, stated in a news release. “Previously, centers with mixing partners had to have Jelmyto mixed and sent by courier in the morning; now this extension provides added convenience of opening up additional scheduling options, which is very important as it enables us to more efficiently manage patient care.”17
The FDA approved an abbreviated new drug application for leuprolide acetate for injection for the palliative management of advanced prostae cancer.18,19 Leuprolide acetate injection is a sterile, aqueous, clear, colorless solution that is administered through subcutaneous injection. The package insert states that a controlled study showed that leuprolide acetate (1 mg/day subcutaneous) had a comparable 2-year survival rate and objective response rate to DES (diethylstilbestrol; 3 mg/day). The insert also recommends monitoring response to leuprolide acetate injection by measuring serum levels of testosterone and prostate-specific antigen.
The FDA has updated the label for avanafil (Stendra) to now include positive clinical trial data for use of the oral erectile dysfunction (ED) drug in men after receiving radical prostatectomy.20 The new data are from a randomized, double-blind, parallel, placebo-controlled trial (NCT00895011) that included 286 patients who experienced ED following radical prostatectomy. The study was a fixed-dose trial with a duration of 3 months. Patients enrolled on the trial experienced ED after receiving a bilateral, nerve-sparing radical prostatectomy. Patients were treated with either 100 mg or 200 mg of avanafil once daily. Both doses administered in the study led to a statistically significant improvement vs placebo for all 3 primary efficacy end points.
The FDA has granted 510(k) clearance to iQuest, an artificial intelligence (AI)–powered software application program for the management of patients with prostate cancer.21 “iQuest combines existing patient-specific diagnostic information and deep-learning algorithms to create a tailored [3D] map of where cancer is within the prostate,” Avenda Health, the develop of iQuest, explained in a press release.21 According to Avenda, iQuest has been validated in multiple clinical studies. For example, clinical data for iQuest were shared during the 2022 AUA Annual Meeting. According to Avenda, the study showed that, “iQuest improved tumor margin creation22 over conventional treatment planning from 56% to 80%23.”
The FDA has approved nadofaragene firadenovec-vncg (Adstiladrin) for the treatment of patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.24 The FDA based its decision on a study that included 157 patients with high-risk BCG-unresponsive NMIBC. Of these patients, 98 had BCG-unresponsive CIS with or without papillary tumors and could be evaluated for response. Overall, nadofaragene firadenovec, which is a non-replicating adenoviral vector based gene therapy, induced a complete response in 51% of patients. The median response duration was 9.7 months. Of the responders, 46% remained in complete response at 1 year.
The FDA has granted a priority review designation to supplemental Biologics License Applications (sBLAs) for the combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) for the frontline treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer.25 The sBLAs are supported by findings from cohorts A and K from the phase 1b/2 EV-103 trial (KEYNOTE-869; NCT03288545). Under the Prescription Drug User Fee Act, the FDA is scheduled to make a final decision on the sBLAs by April 21, 2023.
1. 23andMe receives FDA clearance for direct-to-consumer genetic test on a hereditary prostate cancer marker. News release. 23andMe Holding Co. January 10, 2022. Accessed November 21, 2022. https://bit.ly/3zHqltf
2. U.S. FDA approves FoundationOne CDx as a companion diagnostic for Keytruda (pembrolizumab) to identify patients with microsatellite instability-high (MSI-H) solid tumors. News release. Foundation Medicine, Inc. February 21, 2022. Accessed November 21, 2022. http://bit.ly/3gq9jL0
3. Valencia Technologies announces FDA approval of eCoin therapy to treat urinary urge incontinence. News release. Valencia Technologies Corporation. March 2, 2022. Accessed November 21, 2022. https://bit.ly/35LnYug
4. Rogers A, Bragg S, Ferrante K, Thenuwara C, Peterson DKL. Pivotal study of leadless tibial nerve stimulation with eCoin for urgency urinary incontinence: an open-label, single arm trial. J Urol. 2021;206(2):399-408. doi:10.1097/JU.0000000000001733
5. Axonics receives FDA approval for recharge-free sacral neuromodulation system. News release. Axonics, Inc. March 7, 2022. Accessed November 21, 2022. https://bwnews.pr/3sXb5qv
6. Novartis Pluvicto approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer. News release. Novartis. March 23, 2022. Accessed November 21, 2022. http://bit.ly/36ODPcD
7. Morris MJ, De Bono JS, Chi KN, et al. Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). J Clin Oncol. 2021;39(18) (suppl 15):LB4.
8. Antares Pharma announces FDA approval Of Tlando, an oral treatment for testosterone replacement therapy. News release. Antares Pharma, Inc. March 29, 2022. Accessed November 21, 2022. http://bit.ly/3hW94rn
9. Accord BioPharma announces U.S. launch for Camcevi (leuprolide) injection emulsion for the treatment of advanced prostate cancer in adults. News release. Accord BioPharma. March 31, 2022. Accessed November 21, 2022. https://yhoo.it/3uFHv8s
10. Foresee Pharmaceuticals announces FDA approval of Camcevi for the treatment of advanced prostate cancer; Accord BioPharma to head the U.S. commercialization. News release. Foresee Pharmaceuticals. May 26, 2021. Accessed November 21, 2022. https://prn.to/3wGnEoO
11. Palette Life Sciences announces FDA 510(k) clearance for Barrigel rectal spacer, proven safe and effective at minimizing the harmful long-term side effects of prostate radiation therapy. News release. Palette Life Sciences. June 9, 2022. Accessed November 21, 2022. https://bit.ly/3QrNuHV
12. Renovia receives FDA clearance for leva Pelvic Health System as first-line treatment for chronic fecal incontinence. Renovia Inc. July 7, 2022. Accessed November 21, 2022. https://prn.to/3NNLM0Z
13. Marius Pharmaceuticals receives FDA approval of Kyzatrex, an oral testosterone replacement therapy. News release. Marius Pharmaceuticals. August 2, 2022. Accessed November 21, 2022. https://bit.ly/3OUA0Cx
14. FDA approves darolutamide tablets for metastatic hormone-sensitive prostate cancer. News release. FDA. August 5, 2022. Accessed November 21, 2022. http://bit.ly/3EjRftS
15. Smith MR, Hussain MHA, Saad F, et al; ARASENS Trial Investigators. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386(12):1132-1142. doi:10.1056/NEJMoa2119115
16. Omaha-based MRI medical device company, Bot Image, receives FDA clearance for artificial intelligence software used in detection and diagnosis of prostate cancer. News release. Bot Image Inc. August 8, 2022. Accessed November 21, 2022. https://prn.to/3bItql6
17. FDA authorizes an extension of the in-use period for UroGen Pharma’s Jelmyto admixture to 96 hours following reconstitution. News release. UroGen Pharma Ltd. September 28, 2022. Accessed November 21, 2022. https://bwnews.pr/3UOGbfL
18. Amneal receives FDA approval for leuprolide acetate injection. News release. Amneal Pharmaceuticals, Inc. November 2, 2022. Accessed November 21, 2022. http://bit.ly/3Xl323E
19. Leuprolide acetate injection. Amneal Pharmaceuticals, Inc. August 2021. Accessed November 2, 2022. https://bit.ly/3sQ1LDU
20. New FDA-approved labeling for Petros Pharmaceuticals’ Stendra (avanafil) now includes efficacy data regarding use in men who have undergone radical prostatectomy. News release. Petros Pharmaceuticals, Inc. October 25, 2022. Accessed November 21, 2022. https://bit.ly/3Ev1efM
21. First AI-Powered Precision Oncology Platform for Prostate Cancer Care, iQuest™, Receives FDA Clearance. Published online December 7, 2022. Accessed December 9, 2022. https://prn.to/3FiYl23
22. Priester A, Fan R, Shubert J, Colina J, Rusu M, Sulaiman V, Shao W, Khandiwala YS, Natarajan S, Sonn GA. A novel AI-derived metric identifies favorable candidates for focal therapy of prostate cancer and accurately predicts treatment margin efficacy. American Urological Association; Engineering and Urology Society. New Orleans, LA. May 15, 2022.
23. Priester A, Fan R, Shubert J, Colina J, Rusu M, Sulaiman V, Shao W, Khandiwala YS, Natarajan S, Sonn GA. Defining prostate cancer focal therapy treatment margins with a machine learning model: improvement upon hemi-gland ablation. American Urological Association; Engineering and Urology Society. New Orleans, LA. May 15, 2022.
24. FDA Approves First Gene Therapy for the Treatment of High-Risk, Non-Muscle-Invasive Bladder Cancer. Published online December 16, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-treatment-high-risk-non-muscle-invasive-bladder-cancer?utm_medium=email&utm_source=govdelivery
25. Astellas, Seagen and Merck Announce FDA Acceptance of Supplemental Biologics License Applications for PADCEV® (enfortumab vedotin-ejfv) with KEYTRUDA® (pembrolizumab) for the First-Line Treatment of Certain Patients With Locally Advanced or Metastatic Urothelial Cancer. Published online and accessed December 20, 2022. https://prn.to/3FJNpLf