The FDA’s accelerated approval mechanism enables the drugs that would treat serious diseases with unmet medical needs to be approved based on a surrogate or intermediate clinical end-point.

Continued approval is contingent upon verification and description of clinical benefit in a confirmatory trial.

From the Principal Investigator of the TROPHY Study

Scott T. Tagawa, MD, MS, FACP, Professor of Medicine and Urology at Weill Cornell Medicine, an oncologist at New York-Presbyterian/Weill Cornell Medical Center and Principal Investigator of the TROPHY study, said, “Only a fraction of patients derive long-term benefit from previously approved cytotoxic therapy or immunotherapy, leaving a great unmet need for treatment options for patients with advanced urothelial cancer who have progressed on first- and second-line therapies. The response rate and tolerability seen with sacituzumab govitecan-hziy may provide physicians an effective new treatment option for patients whose cancer continues to progress even after multiple therapies.”

Urothelial cancer is the most common type of bladder cancer and occurs when the urothelial cells that line the inside of the bladder and other parts of the urinary tract express unusual growth. An estimated 83,000 Americans will be diagnosed with bladder cancer in 2021, and almost 90% of those diagnoses will be UC. The relative five-year survival rate for patients with metastatic UC is 5.5%.

From the CEO of BCAN

Andrea Maddox-Smith, CEO of the Bladder Cancer Advocacy Network (BCAN), said, .“Cases of urothelial cancer continue to rise in the U.S., yet the prognosis remains the same for the vast majority of patients. Bladder cancer patients need as many treatment options as possible, and we are pleased that Trodelvy can be a potentially viable treatment for them.”

Trodelvy’s safety profile in the TROPHY study is consistent with previous observations in metastatic UC and other tumor types. Among all evaluable treated metastatic UC patients the most common (≥25%) adverse reactions were diarrhea (72%), anemia (71%), fatigue (68%), neutropenia (67%), nausea (66%), alopecia (49%), decreased appetite (41%), constipation (34%), vomiting (34%) and abdominal pain (31%). Adverse reactions leading to treatment discontinuation occurred in 10% of those receiving Trodelvy, with 4% discontinuing treatment due to neutropenia.

From Gilead Sciences

Merdad Parsey, MD, Ph.D., Chief Medical Officer, Gilead Sciences said, “…This achievement, coupled with last week’s full FDA approval in unresectable locally advanced or metastatic triple-negative breast cancer, underscores our commitment toward rapidly delivering Trodelvy to patients facing some of the most difficult-to-treat cancers.”

A global, randomized Phase 3 confirmatory clinical trial TROPiCS-04 (NCT04527991) is underway and is also intended to support global registrations.

Click here for more information about TROPiCS-04.

The Product, Trodelvy®

Trodelvy is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein frequently expressed in multiple types of epithelial tumors, including metastatic triple-negative breast cancer (TNBC) and metastatic UC, where high expression is associated with poor survival and relapse.

In addition to the accelerated approval of Trodelvy for the treatment of locally advanced or meta-static UC, Trodelvy is approved in the U.S. to treat adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.

Trodelvy® Approvals Abroad

Beyond the regulatory approvals of Trodelvy in the U.S., regulatory reviews for Trodelvy in metastatic TNBC are currently underway in the EU, U.K., Canada, Switzerland and Australia, as well as in Singapore through Gilead Sciences’ partner, Everest Medicines.

Trodelvy is also being developed as an investigational treatment for:

• Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER 2-) metastatic breast cancer
• Metastatic non-small-cell lung cancer. Additional evaluation across multiple solid tumors is also underway.

The Phase 2 TROPHY-U01 study (also known as IMMU-132-06) trial is an ongoing, international, multi-center, open-label, multi-cohort, single-arm study evaluating Trodelvy monotherapy or combination therapy in patients with metastatic UC after progression on a platinum-based regimen and anti-PD-1/PD-L1-based immunotherapy.

TROPHY-U01 Trial Cohorts

• In Cohorts 1 and 2, patients received Trodelvy 10 mg/kg administered intravenously on Days 1 and 8 of a 21-day cycle to be continued until disease progression or loss of clinical benefit. Trodelvy is approved under accelerated approval based on the objective response rate (ORR) and duration of response (DoR) established in Cohort 1.
• Cohorts 2, 3, 4 and 5 of the study are ongoing.
• Cohort 2 is assessing the safety and efficacy of Trodelvy monotherapy in platinum-ineligible patients after progression on anti-PD-1/PD-L1-based immunotherapy.
• Cohort 3 is assessing the safety and efficacy of Trodelvy on Days 1 and 8 of a 21-day cycle followed by pembrolizumab at the standard approved dose (200 mg) only on Day 1 of a 21-day cycle in patients with metastatic UC who have progressed after prior platinum therapy.
• Cohorts 4 and 5 are assessing the safety and efficacy of Trodelvy combination therapy in patients with treatment-naive metastatic UC, with those in Cohort 4 receiving cisplatin and those in Cohort 5 receiving cisplatin and avelumab, respectively, in addition to Trodelvy.

Primary and Secondary Endpoints

• The primary endpoint is ORR based on RECIST 1.1 criteria evaluated by independent central review in all five cohorts.
• Secondary endpoints in Cohorts 1 and 2 are DoR and progression-free survival (PFS) based on central review and overall survival (OS).
• Secondary endpoints in Cohorts 3, 4, and 5 include DoR, clinical benefit rate (CBR) and PFS based on central review by RECIST 1.1 criteria: DoR, CBR, and PFS based on investigator re-view by RECIST 1.1 and iRECIST criteria, OS and safety, and tolerability of Trodelvy in combination with pembrolizumab, cisplatin, or cisplatin and avelumab, depending on the Cohort.

For more Safety Information about Trodelvy please see the press release at the Gilead Sciences website.

Prohost Observations

What we are seeing here is Gilead Sciences, the company that turned the deadly HIV infection into a chronic treatable disease and also cured hepatitis C infected patients for the first time, becoming an oncology firm that treats patients with resistant deadly cancers.

In our opinion, Gilead Sciences is more than scientifically genius; it is ready to make a gamble for the sake of discovering and developing superior future treatments.

It is our belief that the time has finally come for Gilead Sciences’ stock price to be fairly assessed and traded by negative and positive investors alike. We further believe that this stock is way oversold and will rebound, reaching our primary target which can be found in Table #1 of the Prohost Portfolio.

To read more about Gilead Sciences please click here.