New Medicines

Benign prostatic hyperplasia


New molecular entity

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Filing withdrawn
May 22US FDA rejects NDA for fexapotide, citing a need for longer-term safety data [40].
Mar 22Filed in the US for treatment of men with benign prostatic hyperplasia. Nymox intend to submit applications in other major markets in the near term [39].
Dec 21Nymox announces it has completed all the required tasks in preparation for its planned upcoming regulatory submission for fexapotide triflutate for BPH. The company says filings are not planned immediately, because of the usual seasonal delays but they are aiming for approval in major economies around the world, including the United States and Europe [38].
May 21Plans to file in US by Sept 21 [34]
Jan 20It appears that fexapotide is not yet filed in the EU. Nymox announces that it recently received the necessary information regarding the formatting and content of its upcoming regulatory filings for fexpotide triflutate to treat BPH in men. The company is proceeding to integrate safety data from its four PI and PII BPH clinical trials as well as the safety data from Prostate Cancer Study NX03-0040 into the final dataset (that also includes 4 PIII trials) that will be part of the New Drug Application (NDA) submission. The filings seeking approvals in the US and in Europe are now targeted for H1 2020 in both jurisdictions. Nymox does not have any barriers to report and does not expect any delays [33].
Nov 19EU development appears to be delayed. In a press release published in Oct 19, Nymox states that management continues to work extremely hard and diligently towards completing the preparatory work necessary for submitting the applications for marketing approval both in the US (NDA) and in Europe (MAA). The Company is currently preparing to seek similar formal clarification from the authorities on data formatting and standardisation for the filings which is a necessary step and which it expects to receive in the near future. After the latter, the Company expects to be able to report to shareholders with further precision about expected timelines for the two filings. Because the data involved in the program has extended over a very long time period (which is a positive), it has also generated additional requirements of data formatting updates and other specific procedures for the filings [32].
Nov 19Nymox annual report, published Mar 19, states that Nymox has filed for regulatory approval in Europe and intends to file with the FDA later this year. Fexapotide is not listed in CHMP lists of medicines under evaluation in 2018 and 19, so it must be assumed that Nymox has filed via the decentralised procedure [30,31].
Apr 19Nymox has a pre-New Drug Application (NDA) Chemistry Manufacturing and Controls meeting with FDA regarding fexapotide triflutate, and hopes to file in the US by end of 2019 [29].
Jul 18Nymox resubmits an expanded application, which will replaces the previous applications, and will greatly facilitate the overall drug-distribution logistics and annual post-marketing safety filing requirements in Europe. The increased manufacturing capacity will be necessary to meet anticipated demand across all European jurisdictions and worldwide [27].
May 17Nymox files for approval in five European countries, the Netherlands, UK, Germany, France and Spain [26].
Jul 15Nymox now intends to meet with authorities with extension data and to proceed to file where possible in due course for regulatory approvals for fexapotide triflutate in various jurisdictions and territories [24].
Apr 15Recordati, the licensee in Europe, the Middle East, North Africa and South Africa, discontinued development and commercialisation activities in its licensed territories after two pivotal PIII trials for BPH conducted by Nymox failed to meet primary efficacy endpoints. Nymox expects to continue its development efforts for BPH in the US [23].
Feb 13A Safety Monitoring Committee review highlighted no safety concerns [16].
Feb 12PIII study to start in EU [9].
Oct 09PIII studies in US [3].
Aug 09PII trials [1].


Apoptosis stimulant
BPH affects about 40% of men in their fifth decade and 90% of men in their ninth decade. It is unusual before the age of 45 and affects men of Afro-American origin more severely than white men [15]
Benign prostatic hyperplasia

Trial or other data

Dec 21Fexapotide was prioritised for potential NICE TA guidance production in Mar 2018, but as of Dec 2021 has never been added to the NICE work programme [37].
Oct 19Updated long-term efficacy data from the PIIb NX03-0040 trial released by Nymox. New long-term data (78 months) (n = 146) showed a 73% reduction in need for surgery or radiotherapy associated with much more favourable biopsy Gleason results vs. controls (p=0.0024) in men who received the high dose fexapotide 15mg single dosage treatment. An increase in Gleason primary pattern grade in the 78 month study was shown in 5% patients in the entire fexapotide group (high dose and low dose) vs. controls where incidence of grade 4 or higher primary pattern was 26.3%, a reduction of 81% (p=0.0037). All recorded instances of surgery or radiotherapy, including elective cases without Gleason upgrades, were decreased by 65.4% (p=0.0014) in fexapotide 15mg treated patients vs. the randomised control group, after 78 months. Several other parameters were significantly better in the fexapotide treated groups vs. controls [28].
Oct 18Fexapotide triflutate is administered at an outpatient visit and consists of a single painless injection that takes a few minutes or less, with no requirements of anaesthesia, or analgesia or catheterization. Nymox claims it has none of the typical sexual and other distressing side effects seen with conventional BPH treatments [26].
Aug 16New long-term fexapotide placebo crossover PIII data show significant reduction in incidence of surgery for symptoms of BPH. Analysis (n=391) reported 82-95% relative reduction in number of blinded placebo patients who subsequently received surgical treatment over 2-3 years for BPH symptoms after receiving crossover fexapotide vs. patients crossed over to conventional treatments (p<0.0001) [25].
Jul 15Nymox announces that an extension of two PIII have produced positive results. After 3.5 years, there were positive long-term improvements in symptoms of BPH, fewer BPH surgeries and a good safety profile. Nymox announced plans to take a look at the post-12-month data in April. Additional new blinded protocol data from the same pivotal studies was prospectively captured in order to assess long-term results in patients up to 5 years after a single injection of NX-1207 2.5 mg vs placebo [24].
Nov 14Nymox reports that two PIII studies failed to meet their primary efficacy endpoints. Full results will be reported at a later date. Drug safety was “acceptable”, and while “efficacy reached levels similar to earlier studies it was not statistically significant vs. placebo due to a higher placebo response. Nymox considers that the compound remains promising for low-grade localised prostate cancer where PII results showed evidence that NX-1207 had a positive effect on biopsy results and clinical and biochemical progression. The drug is partnered with Italy’s Recordati which holds EU & other non-US rights to the drug in BPH [22].
Jul 14New positive efficacy data for U.S. Study NX02-0022; symptomatic improvement from repeat injection over a 1 to 2 year period showed a mean improvement of 8.2 points (p <.001) in the AUA BPH Symptom Index Score. Safety data from this study confirmed that NX-1207 reinjection treatment was well-tolerated by pts, did not impair sexual function, and not shown any drug-related significant side effects. [21]
Jul 14Pivotal EU PIII NCT0200374 study is still recruiting pts. Anticipated date primary outcome data collected is Jul 2016 [20].
Jul 14PIII NCT01846793 study is continuing to recruit pts. Anticipated date primary outcome data collected is Oct 2014 [20].
Mar 14No update available on progress of PIII NCT01846793 study [19].
Aug 13Both PIII studies are fully enrolled and the latest periodic review of safety data for one of them, NX02-0018, found no significant safety concerns [18].
May 13EudraCT2012-002451-41 is a PIII randomised, single-blind placebo-controlled European study of NX 1207 (with/vs tamsulosin?) in 340 patients with BPH on adequately controlled on a alpha-blocker. NX-1207 will be given as a single transrectal-ultrasound (TRUS)-guided intraprostatic injection. The primary outcome is improvement of lower urinary tract symptoms as assessed by a change from baseline in the total score (Questions 1 to 7) of the International Prostate Symptom Score (IPSS) 12 months after randomisation. The study started in May 2013 and may complete 2015/2016 [17].
May 13Patient enrollment in the final pivotal US PIII NX02-0018 is complete. Top-line results are expected early 2014 [14]
May 13NCT01846793 is a PIII multicentre open label clinical safety evaluation of re-injection (two doses 1-8 years apart) of NX-1207 for the treatment of 200 men with BPH. The study started Apr 13 and is due to complete Mar 14 [13].
Jan 13Topline results reported from the US study NX02-0020. Study participants consisted of 192 consecutively treated men who had previously participated in other trials and who wished an open label injection of NX-1207. Improvement in the American Urological Association BPH Symptom Index Score was assessed over 26 months; the mean overall improvement was 7.6 points (p <.001). The study has completed its 6 month primary endpoint of the safety evaluation of re-injection. No significant AEs occurred; it was not associated with sexual or cardiovascular side effects [12].
Oct 12The Independent Data Monitoring Committee for the PII study of NX-1207 for low risk localized prostate cancer (NX03-0040) has reported a second positive analysis of safety data from the clinical trial. Pts who had received high dose NX-1207 prostate cancer were assessed [11].
Sep 12The Safety Monitoring Committee review for the NX02-0020 trial was favorable and indicated no significant safety concerns for the trial to date. Patient recruitment for the trial is complete with top-line efficacy results expected near the end of this year [11].
Aug 12A new study of long-term treatment outcomes found that a statistically significant greater number of men who had received NX-1207 2.5 mg reported positive treatment outcomes as compared to men who had received a placebo (p=.02). The study involved the latest available blinded follow-up study data (an average of 57 months post-injection) from the completed clinical trials for these treatment groups. A positive treatment outcome was seen if the pt was not using other BPH medications and no surgical treatment (including MIST) for BPH was reported at any time during the post-injection follow-up period [10].
Feb 12A European PIII trial is to start following discussions with the EMA. The trial will assess the efficacy and safety of a single TRUS-guided intraprostatic injection of NX-1207 in patients with lower urinary tract symptoms (LUTS) associated with BPH not adequately controlled by medical therapy. A European licensing agreement for the development and commercialization of NX-1207 was signed on 16 December 2010 by Recordati and Nymox [9].
Sep 11NCT01438775 – is a PIIII multicenter prospective open label safety evaluation of re-injection of Nx-1207 in 250 patients who have received a first injection as part of a previous clinical trial. The second dose will be given between 1-7 years after the first. The study will start Sep 11 and is due to complete Jul 12 [8].
Mar 11Further results from a long term outcome study reported which enrolled patients involved in the NX02-0012 and NX02-0013 PI/II studies undertaken in 2003. Overall, 58% of men reported no subsequent surgical treatment and no current drug treatment for their BPH and had an ongoing mean improvement of 11.7 points in AUA BPH Symptom Score 7 ½ years after a single treatment of NX-1207. 38% reported no prolonged use of any approved treatments at any time for their BPH since their original treatment with NX-1207, with a mean improvement of 13.7 points [7].
Dec 10Recordati has bought the European rights to NX-1207 from Nymox [6]
Oct 10The Safety Monitoring Committee meeting for the two ongoing US PIII studies (NX02-0017 and NX02-0018) was favorable and indicated no significant safety concerns. 70 US urology centres are involved in patient recruitment and trial activities [5].
May 10results announced from a long-term outcome study. The study evaluated symptomatic progress after 6.5 years of patients, on an unselected and as available basis, who had a received a single treatment with NX-1207 in the NX02-0012 and NX02-0013 PI/II studies undertaken in 2003. Data were available for 69% of the patients from these studies. Overall, 55% reported no subsequent surgical treatment and no current drug treatment for their BPH and had a mean improvement of 14.3 points in AUA Symptom Score. In addition, 36% reported no other approved treatments at any time for their BPH since their original treatment, with a mean improvement of 14.5 points [4].
Oct 09An analysis of pooled data from PII double-blind follow-up studies involving 159 men reported by the company. A statistically significant difference in standardised BPH symptom score improvement at a mean of 13.5 months after a single injection was found between NX-1207 2.5mg and placebo. The median improvement in BPH Symptom Score with NX-1207 at 12 months was 9 points (p<0.003) [3].
Oct 09In two multi-centre PII US prospective randomized blinded trials, the aggregated mean improvement in the BPH symptom score for 2.5mg NX-1207 was 10.3 points (increase of 44%) at 3 months. By comparison, currently approved drugs for BPH provide on average 3 to 5 points improvement according to the company, and often have unwanted side effects such as impotence, loss of libido, retrograde ejaculation, dizziness, and weakness [3].
Oct 09NX-1207 is injected by a urologist in an outpatient setting directly into the zone of the prostate where the enlargement occurs. The procedure lasts on average 5-10 minutes, with the injection taking 1-2 minutes, does not require anaesthesia or catheterization [3].
Feb 09At 12 months post-treatment, more than seven times as many positive responses to treatment were documented in patients who received NX-1207 compared to patients who received finasteride. A positive response was defined as a 9 point or more BPH Symptom Score improvement without any subsequent BPH treatments of any kind, and corresponded to a minimum 37.5% improvement in BPH symptoms. The difference in response rate between NX-1207 and the comparator was statistically significant (p=.01). The range of improvement in individual patients who received NX-1207 and were categorised as responders was 37.5 to 93% reduction in symptoms. Overall, 76.7% of subjects who received a single dose of NX-1207 reported no further BPH treatment after 12 months (p=.01). (2)
Jan 09Safety results from PII study - no serious drug side effects revealed. NX 1207 has also completed two Phase I and II studies - caused ~ >23% prostate shrinkage in 1 month with minimal side effects(1).

Evidence based evaluations