StemCell Therapy

As expected, G1 Therapeutics Inc.s Cosela (trilaciclib) won FDA approval for use in extensive-stage small-cell lung cancer (SCLC) patients undergoing chemotherapy, becoming the first proactively administered myelopreservation therapy to hit the market.

The approval, conducted under the FDAs priority review, came late Feb. 12, just ahead of its Feb. 15 PDUFA date. Pricing has not yet been disclosed, but Research Triangle Park, N.C.-based G1 spent the latter half of 2020 prepping for commercial launch in the first quarter of 2021, with marketing, medical affairs and manufacturing operations fully in place and a field sales team from U.S. partner Boehringer Ingelheim GmbH trained and ready, the company reported during its presentation at the 2021 J.P. Morgan Healthcare Conference.

There are roughly 30,000 ES-SCLC patients treated annually in the U.S.

Chemotherapy remains the primary therapy for SCLC etoposide, topotecan, irinotecan and platinum-based drugs such as cisplatin or carboplatin, for example but its use results in damage to bone marrow stem cells, leading to myelosuppression. That, in turn, results in symptoms such as anemia, neutropenia or thrombocytopenia, which not only affects patients quality of life but can also disrupt treatment cycles and impact overall survival.

Some drugs are available to mitigate the damage. G-CSF drugs, for instance, are designed to prevent febrile neutropenia resulting from chemotherapy and erythropoiesis-stimulating agents are used to keep anemia in check. But those usually have their own treatment-limiting side effects.

Preserving immune function

Trilaciclib, a CDK4/6 inhibitor that received an FDA breakthrough therapy designation, is designed to preserve bone marrow and immune system function during chemotherapy treatment. Approval was based on data pooled from three pivotal studies that read out over 2018 and 2019.

In December 2018, G1 reported top-line data from its randomized, double-blind, placebo-controlled phase II trial evaluating combination of the therapy with topotecan as a treatment for second- and third-line SCLC, showing trilaciclib reduced clinically relevant consequences of myelosuppression vs. placebo. The trilaciclib arm demonstrated statistically significant reductions in both the duration of grade 4 neutropenia in cycle one (mean eight days vs. two days; adjusted one-sided p<0.0001) and occurrence of grade 4 neutropenia (75.9% vs. 40.6%; adjusted one-sided p=0.0160) as compared to the placebo arm.

Data from a phase II study testing trilaciclib with the combination of etoposide/carboplatin for the treatment of first-line SCLC demonstrated clinically meaningful improvements for neutrophil, red blood cell and lymphocyte measures in patients vs. placebo. In regard to lymphocytes, in particular, trilaciclib preserved or improved B-cell and T-cell subset counts, including activated CD8-positive cells, and increased CD8-positive/regulatory T-cell and activated CD8-positive/regulatory T-cell ratios in peripheral blood compared to placebo.

It also showed benefit in another phase II study in combination with chemotherapy and Tecentriq (atezolizumab), the PD-L1 inhibitor from Roche Holding AG. Data showed statistically significant improvements in both primary endpoints of occurrence of grade 4 neutropenia and duration of grade 4 neutropenia in cycle one, as well as a statistically significant reduction in grade 4 thrombocytopenia and clinically meaningful reduction in red blood cell transfusions. Trilaciclib reduced clinically relevant consequences of myelosuppression vs. placebo when administered in combination with chemotherapy (etoposide and carboplatin) and Tecentriq across neutrophils, red blood cells and platelets.

An established sales team

G1s three-year, SCLC-focused co-promotion deal with Boehringer, inked in June 2020, calls for G1 to lead marketing, market access and medical engagement initiatives, which are expected to extend to a focus on updating NCCN clinical practice guidelines to include trilaciclib. Boehringer brings to the table the established lung cancer sales team. Under the terms, G1 will book revenue and retain development and commercialization rights, paying Boehringer a promotion fee determined by net sales.

H.C. Wainwright analyst Edward White in Nov. 5, 2020, note, said he estimates trilaciclib sales of $21.4 million in 2021.

G1 also is looking to expand use of the drug beyond SCLC. In December, the company reported phase II data at the San Antonio Breast Cancer Symposium showing significantly improved overall survival in patients with triple-negative breast cancer (TNBC) treated with trilaciclib in combination with gemcitabine/carboplatin (GC) vs. GC alone. G1 plans to launch a registrational study this year to test trilaciclib plus GC in first-line patients with metastatic TNBC who have not received a PD-1/PD-L1 inhibitor and in second-line patients with metastatic TNBC who have received prior PD-1/PD-L1 therapy.

Trilaciclib also is included in the ongoing pivotal I-SPY 2 study in neoadjuvant breast cancer.

In August 2020, G1 licensed greater China rights for trilaciclib to Simcere Pharmaceutical Co. Ltd. in a $170 million deal.

Shares of G1 (NASDAQ:GTHX) were trading up 12% in after-hours trading Feb. 12.

Read more from the original source:
G1 Therapeutics gains first FDA nod with myelopreservation therapy Cosela | 2021-02-12 - BioWorld Online

This entry was posted on February 14, 2021 at 7:21 pm and is filed under Stem Cell Negative. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |