The administrative interim analysis of three-month efficacy proved disappointing in Sophiris Bio Inc.'s 12-month phase III PLUS-1 trial with PRX302 (topsalysin) for benign prostatic hyperplasia (BPH), but CEO Randall Woods advised investors to "just sit tight for right now," since the peek is "just a snapshot" done for planning purposes.

"I'm quite confident that we can still achieve the primary endpoint," Woods told BioWorld Today, noting that the trial is "90 percent powered to show a 2.5-point treatment effect at a very conservative standard deviation of 8 or less." The commonly deployed International Prostate Symptom Score will be used to measure the change from baseline.

Wall Street, though, reacted harshly, and shares of La Jolla, Calif.-based Sophiris (NASDAQ:SPHS) closed Monday at 52 cents, down $2.30, or 81.5 percent.

"There is no alpha spend on the interim analysis," Woods noted, so management remains blinded to the results, and the point at which the primary-endpoint efficacy will be determined is still nine months away. "Had we gotten a thumbs-up on [the interim look], it would have given us more confidence to move forward, to spend some money and time on beginning to initiate preparation for the second trial." The $65 million that Sophiris banked from an initial public offering has been pledged to finish the first of potentially two phase III trials in BPH. "We have the cash to get us all the way through the final result of the BPH trial, maybe with some additional runway beyond that," Woods said. (See BioWorld Today, Feb. 20, 2013.)

In early November, Hasbrouck Heights, N.J.-based Nymox Pharmaceutical Corp. said a pair of phase III studies with NX-1207 for BPH, known as NX02-0017 and NX02-0018, failed to meet their primary endpoints in top-line results, and the company blamed a strong placebo response – stronger than was seen in previous experiments. (See BioWorld Today, Nov. 4, 2014.)

"I don't think it's been publicly disclosed what the Nymox drug was and that's why it's difficult to draw any comparisons between our drug and theirs," Woods said, acknowledging that results with prostate scoring can be tricky since they are patient-reported outcomes. "We have put in place as many safeguards as we possibly can to minimize on overstated placebo effect, but you can never take that risk to zero in a more subjective endpoint like this," he said. Nymox's shares (NASDAQ:NYMX) closed Monday at 40 cents, up 20.8 percent.

"From a drug perspective, it was really just Nymox and ourselves," Woods said. Other options in BPH aren't great, such as oral medications (which bring cardiovascular and sexual side effects and/or quit working) and transurethral resection of the prostate (which means catheterizing the patient and can bring bleeding and erectile dysfunction).

NEXT UP: PROSTATE CANCER

As the BPH data mature, Sophiris is putting together a proof-of-concept study with the same therapy in localized prostate cancer. "We only recently got the protocols well defined and everything in place so that we feel comfortable talking about it," he said. During the planning of the BPH study, key opinion leaders suggested that PRX302's mechanism of action could make it ideal for the localized PC indication. "A theme that emerged was difficult to ignore," Woods said, predicting that the PC market value "could actually eclipse BPH," though both are huge. "I think [PRX302] could revolutionize the way localized prostate cancer is treated," he said.

"It's brilliant the way the drug is designed," Woods said, calling the approach "really quite straightforward." The protein is "genetically modified such that it actually gets recognized and then cleaved only by enzymatically active prostate specific antigen [PSA]," he said, and in the body PRX302 "very quickly binds to glycosylphosphatidyl inositol-anchored receptors that are right on the cell surface, and are bathed in enzymatically active PSA. When our drug comes in contact with the PSA, it clips off the inhibitory tail and activates the drug, and then the drug forms pores that basically drill down into the membrane of the cell and cause the cell contents to leak out." No systemic exposure takes place since the drug otherwise remains inert, added Woods, calling PRX302 "the safest drug I've ever worked on."

He cited "a lot of buzz in the urology community" about treating localized PC, thanks to improved imaging techniques. Doctors now have "very clear, three-dimensional images on the magnetic resonance imaging [tests] that they can sync up with the ultrasound," so that biopsies are no longer a "shot in the dark," Woods said. Thus, PRX302 could be precisely injected – and even if it misses a little, the consequences are nil. Other treatments for localized PC include radiation and surgery, with "a lot of morbidities," Woods said. "I haven't talked to a male patient yet who's had that done and is happy with the results."

To pay for the PC study, Sophiris in May entered a stock purchase agreement with Aspire Capital Fund LLC, which started off with a buy of 604,320 common shares at $3.31 per share for proceeds to Sophiris of $2 million. Aspire committed to buy up to $13 million more shares over the next 30 months at prices based on market price at the time of each sale. The six-month PC study should yield data right around the time when the final BPH results are available, "maybe a little bit sooner," Woods said. Meanwhile, he said, the firm is not disheartened by the latest, stock-battering news. "Things can completely change by then. This is drug development. This sort of thing happens all the time."