Oral CDK4/6 inhibitors like Pfizer’s Ibrance and Lilly’s Verzenio have established themselves as first-line treatments for hormone receptor-positive, Her2-negative breast cancer, but G1 Therapeutics reckons it has hit on something new: its CDK4/6 project trilaciclib aims to improve patients’ tolerance of chemotherapy.
Yesterday the group climbed 24% on the news that in a triple-negative breast cancer (TNBC) study trilaciclib statistically improved overall survival, even though the real benefit remains ill defined. However, G1 has an aggressive filing plan, and might now be planning an equity raise.
Yesterday’s revelation, a short update to the open-label data G1 had presented at last year’s San Antonio Breast Cancer Symposium, provided some relief to a stock price that still stands 64% below its September 2018 high.
G1 had raised $105m in a May 2017 IPO, and it must be stressed that, with $348m in the bank, the group is not in desperate need of cash. However, as Biohaven has demonstrated, biotechs raise money not when they need it but when they can.
G1’s San Antonio data had shown trilaciclib plus chemotherapy numerically increasing TNBC subjects’ remissions and progression-free survival versus chemo alone, though neither increase was statistically significant.
Yesterday the company said overall survival, a measure that in December was still immature, was statistically improved in trilaciclib subjects in this study. However, it revealed no numbers, meaning that the clinical meaningfulness of this benefit cannot at present be gauged.
Investors might well ponder on what an appropriate measure of trilaciclib’s activity might be, since efficacy would be derived from chemo, whereas trilaciclib’s purported role is improving chemo’s tolerability. It is therefore feasible that the G1 project might help patients live longer even if it has no impact on disease progression.
The San Antonio data revealed did not suggest much of a safety advantage for trilaciclib, though researchers argued that some myelosuppression events were reduced in patients given the G1 project.
G1 itself says that trilaciclib’s main effect is on myelopreservation, to protect the bone marrow from damage by chemotherapy. The project is dosed IV rather than orally, and is short-acting, but even G1 admits in SEC filings that scientific evidence to support developing it is “both preliminary and limited”.
|G1's clinical studies of trilaciclib|
|2nd-line (post topotecan) SCLC||Topotecan combo||NCT02514447|
|1st-line SCLC||Carboplatin + etoposide combo||NCT02499770|
|1st-line SCLC||Carboplatin + etoposide + Tecentriq combo||NCT03041311|
|Various lines of TNBC||Carboplatin + gemcitabine combo||NCT02978716|
The company says it plans to file a US NDA next year based on data it has already generated in three randomised, double-blind, placebo-controlled SCLC trials; an EU submission will follow.
It was SCLC that gave the company its first taste of success. In March 2018 it said a phase II clinical trial had shown statistically significant reductions in neutropenia and other adverse events among a cohort of 75 treatment-naive SCLC subjects – though remissions and PFS only showed “trends” favouring trilaciclib.
It should also be remembered that G1 is separately pursuing a more traditional CDK4/6 approach, developing an oral inhibitor coded G1T38. This, it says, was rationally designed to improve on Ibrance and Verzenio’s shortcomings, and will target the established setting of HR-positive, Her2-negative breast cancer.
The primary focus, however, remains trilaciclib and its potential to make chemo more tolerable. Given that treatment paradigms are already changing, with Roche’s Tecentriq approved in first-line TNBC and SCLC, G1 has a small window of opportunity.