Halozyme Therapeutics Inc. said it is working quickly to assess an unexpected imbalance in thromboembolic event rate between treatment and control groups, which prompted a halt to its phase II trial testing PEGPH20 in pancreatic cancer, though the lack of detail left room for plenty of speculation.

The big worry, of course, if that it might be linked to the platform technology that underlies Halozyme’s entire pipeline. Based on the recombinant human hyaluronidase enzyme (rHuPH20), which degrades hyaluronan (HA), the technology can be formulated with existing drugs to allow for more convenient subcutaneous delivery; it can also work on its own, breaking down the HA that accumulates around tumors and protects them.

While it has had its successes – so far, two Roche AG drugs, rHuPH20 versions of Herceptin (trastuzumab) and Mabthera (rituximab) have cleared European regulatory approval and rHuPH20 product Hylenex has gained approval in the U.S. – the technology has seen its share of troubles, too. Last year, Halozyme discontinued a phase II study testing a subcutaneous version of Viropharma Inc.’s hereditary angioedema drug Cinryze (C1 esterase inhibitor) because of high levels of non-neutralizing antibodies. (See BioWorld Today, Aug. 2, 2013.)

The same glitch occurred previously, with a rHuPH20 version of Baxter International Inc.’s HyQ, plasma-derived immune globulin 10 percent, which earned a complete response letter in 2012. Baxter resubmitted in the fourth quarter of last year. (See BioWorld Today, Aug. 3, 2012.)

As Jefferies analyst Eun K. Yang noted in a research report, given that Halozyme’s value “is entirely based on its rHuPH20 platform, any potential safety issues could have broad implications in valuation.”

That was clearly felt on Wall Street, which sent shares of Halozyme (NASDAQ:HALO) falling $3.16, or 27.3 percent, to close Friday at $8.43.

Piper Jaffray analyst Charles Duncan, however, is not convinced the latest clinical snafu translates into a flaw in the rHuPH20 technology. “We don’t see this as a problem for the broad platform as the dosing paradigm is different with the technology in the approved uses (Hylenex) vs. the PEGHPH20 pancreatic trial (intravenous),” he wrote in a research note.

Unlike the subcutaneous rHuPH20 Cinryze trial, antibodies weren’t an issue in the pancreatic cancer study (Study 202), which evaluated PEGPH20, a pegylated version of rHuPH20, in combination with Abraxane (nab-paclitaxel) and gemcitabine vs. Abraxane and gemcitabine alone. Instead, the data monitoring committee noted a possible difference in thromboembolic events. Enrollment and dosing were stopped as a precautionary measure while investigators determine whether those events are treatment-related.

Halozyme said the halt is expected to be temporary, and Piper Jaffray’s Duncan agreed. “Our diligence indicates the resolution goal is ‘weeks, not months,’” he wrote.

Duncan also pointed out that the safety issues could stem from the interaction of Abraxane, which was not included in previous trials.

PEGPH20 previously was tested only in combination with gemcitabine, the then-standard of care, in a phase Ib trial. But last year’s approval of Celgene Corp.’s Abraxane set a new – albeit modestly raised – standard for treatment, so it made sense for Halozyme to incorporate Abraxane in further testing. (See BioWorld Today, Sept. 9, 2013.)

And it’s not the only company to do so. According to Cortellis Clinical Trials Intelligence, Oncogenex Pharmaceuticals Inc. is in a phase II trial testing heat-shock protein 27 inhibitor in combination with gemcitabine and Abraxane in metastatic pancreatic cancer, and a similarly designed phase II trial is ongoing to test Cantex Pharmaceuticals Inc.’s ODSH (2-0, 3-0 desulfated heparin).

Halozyme also is testing PEGPH20 in a phase Ib/II study, sponsored by cancer research cooperative SWOG, that combines it with a modified FOLFIRINOX regimen. FOLFIRINOX, a cocktail comprising chemo drugs oxaliplatin, irinotecan, fluorouracil and leucovorin, is the only treatment to date that has proved more effective than gemcitabine in pancreatic cancer, but its toxicity prevents physicians from using it in the majority of advanced disease patients.

It is not clear yet whether the safety issues is Study 202 will affect the PEGPH20/FOLFIRINOX trial, which is enrolling about 144 patients and will measure overall survival as the primary endpoint.

Elsewhere in the pipeline, Halozyme has midstage program that combines rHuPH20 with analogue insulin, and recently reported positive phase I/II data for HTI-501, a recombinant human cathepsin L that marks the firm’s first conditionally active biologic and is in development for treating cellulite.

As of Dec. 31, Halozyme had about $71.5 million on its balance sheet.