- Novogen Ltd. has tapped Chiltern International to help conduct Phase 2 testing of the drugmaker's lead pipeline candidate, which is slated to begin in the fourth quarter.
- Specifically, the companies will evaluate the candidate, GDC-0084, as a treatment for patients with the fast-growing brain cancer known as glioblastoma multiforme (GBM). Novogen in-licensed the drug from Genentech Inc. in 2016 after the Roche subsidiary conducted a Phase 1 trial investigating it in people with progressive or recurrent high-grade brain tumors.
- Since its deal with Genentech, Novogen has secure patents for GDC-0084 in the U.S., Australia, and a few other regions, according to a Tuesday statement from the Australian pharma.
GDC-0084 works by inhibiting the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) cell signaling pathway. Research has shown that, when this pathway mutates, it can aid in cancer development. As such, many drugmakers — from Novartis International AG to Verastem Inc. — have snagged their own PI3K/Akt inhibitors and investigated them in the clinic across a variety of tumor types.
Novogen, however, believes its drug has a leg up on the competition. Compared to other medications in the class, GDC-0084 more easily crosses the blood-brain barrier, a semipermeable membrane that is highly effective at keeping substances in the blood stream away from the brain, meaning it could be an effective treatment for central nervous system cancers, according to Novogen.
Traditionally, the blood-brain barrier has been a difficult obstacle for brain cancer drugmakers to tackle.
"The GDC-0084 study is on track to commence this year, in line with our prior guidance to the market," Novogen CEO James Garner said in an Aug. 22 statement. "The need for new therapeutic options in brain cancer is substantial, and we hope that GDC-0084 will have an important role to play."
Gilead Sciences Inc.'s Zydelig (idelalisib) was the first PI3K inhibitor to gain approval from the Food and Drug Administration back in 2014. So far, the product has largely fell short of expectations.
On the positive end, revenues have grown — Zydelig sales totaled $168 million in 2016, up 27% from 2015. But on negative end, it carries a black box warning for fatal and serious toxicities, diarrhea, intestinal perforation, and colon and lung inflammation. Last year, Gilead paused six clinical trials of the drug after a review from the European Medicines Agency started investigating higher rates of adverse events, including infection-related deaths, among patients treated with Zydelig.
For Novogen, results from Phase 1 dose-escalating trial of GDC-0084 showed that, of the 47 patients enrolled, there was one case each of Grade 2 bradycardia and Grade 3 myocardial ischemia at a 15 mg dose, one case of Grade 3 at the 45 mg dose and two cases of Grade 3 mucosal inflammation at the 65 mg. Novogen has characterized the drug's safety as "well-tolerated."
Going forward, Novogen plans to iron out study details with the FDA before kicking off its Phase 2 program. The company's newly minted Master Services Agreement with Chiltern lays out most of the terms of the contract research deal, but there's built in flexibility to take into account FDA recommendations.
Stemming from the Genentech deal, Novogen also has about 48 kg of GDC-0084 drug substance, part of which has already been made into capsules for the Phase 2 trial, according to the Aug. 22 statement. Those capsules are currently under review.
Novogen stock barely changed on Tuesday, up less than one percent to $3.21 per share.