At once, Keryx Biopharmaceuticals is a very different company. The phase III failure of perifosine in metastatic colorectal cancer caused company executives to cast doubt on the compound’s future in its other advanced-stage indication, multiple myeloma, and their emphasis abruptly pivoted to hyperphosphataemia candidate Zenerex.
Shares of the New York company took a pounding on the news, dropping by nearly two-thirds to a 30-month low of $1.74 Monday as hopes for the drug evaporated. The setback also demolished any near-term chance of a takeout, and certainly puts Keryx on the back foot in partnering talks on Zenerex.
Shares in licensor Æterna Zentaris, which retains European marketing rights, also collapsed on the news, falling 66% to 73 cents. The agent represented the Canadian company’s largest growth driver, with forecast sales of $107m in 2016 and another $87m in royalties, according to EvaluatePharma data.
Also known as KRX-0401, perifosine is the first phosphatidylinositol 3-kinase (PI3K) inhibitor to report phase III results, and as one of the few candidates in the class that had not attracted a big-name partner was suspected to be a high-risk asset (Event - Expectations building for Keryx cancer drug, March 6, 2012). Keryx investors had clearly rallied behind it, with the share price nearly doubling since the start of 2012 until yesterday, but it was also heavily shorted – 19% of shares had been sold by investors betting on a big fall in the near future.
In combination with capecitabine, perifosine failed to improve overall survival in patients with refractory advanced colorectal cancer when compared to capecitabine alone. In an unusually apologetic call with investors, chief executive Ron Bentsur said patients in the capecitabine-only arm survived significantly longer than historical averages, making the job of showing a survival advantage for perifosine difficult; the company did not release details beyond the topline result.
Mr Bentsur acknowledged the colorectal cancer results may have knock-on effects on its other phase III trial, casting a shadow over the whole programme. He said the company had experienced difficulty recruiting the necessary 450 patients into the multiple myeloma study, and news of the failure was likely to discourage enrolment.
Thus the next major catalyst for Keryx is readout of Zerenex phase III data to treat phosphataemia in patients with end stage renal disease, expected by the end of 2012 (Therapeutic focus – Phosphate binders seeking safety in small numbers, December 8, 2010). Mr Bentsur said the company had $31m at the end of March, and will focus most of its resources on completing the Zerenex research and submitting regulatory applications in the US and Europe.
A blow for PI3Ks
As the first in the PI3K class to report late-stage results, the result for perifosine could prompt worries for others working with similar agents - although many considered it a less attractive data than other candidates in the class.
The PI3Ks mechanism of action is thought to be able to combat the drug resistance that has troubled many targeted agents, and much expectation is building around them (Therapeutic focus - PI3Ks in the spotlight in 2012,January 27, 2012). With Keryx’s clear de-emphasis on perifosine, however, the PI3K spotlight will turn elsewhere.
The next data point is likely to come mid-year in the form of phase II results from Gilead Sciences’ GS 1101 in Hodgkin lymphoma or Novartis’ BKM120 in breast and brain cancer. Celgene’s TORKi and Oncothyreon’s PX-866 are expected to report by year’s end.
Still, hopes that one of these new compounds would very soon be in the hands of physicians treating advanced cancer have now all but disappeared. Keryx has made it clear that it has waning interest in pursuing this avenue of research; success appears to be years away.