ESMO: New Trodelvy breast, bladder cancer data show why Gilead’s going big for Immunomedics

By | September 21, 2020

Compared with the spate of multibillion-dollar buyouts last year, biopharma M&A has been relatively quiet in 2020—until last week, when Gilead Sciences surprised the market with its $ 21 billion purchase of Immunomedics.

Now, two sets of new cancer data from Immunomedics’ first-in-class antibody-drug conjugate Trodelvy offer a glimpse into why Gilead paid such big money for the biotech—even as they illuminate the potential competition ahead.

In Trodelvy’s FDA-approved indication of metastatic triple-negative breast cancer, the anti-TROP-2 drug cut the risk of disease progression by 59% over chemotherapy in patients who had previously failed on at least two chemo regimens.

More importantly, the phase 3 Ascent trial presented Saturday at the European Society of Medical Oncology’s virtual congress showed Trodelvy also helped patients live longer, cutting the risk of death by a whopping 52%. Those on Trodelvy lived a median 12.1 months, compared with just 6.7 months for chemo patients.

As Ascent trial investigators pointed out, Trodelvy is the first ADC to show significant survival improvement over standard chemo in this heavily pretreated TNBC population. The data will likely help Immunomedics turn its conditional FDA nod, earned in April, into a full one.

But while Trodelvy holds the ADC lead in TNBC, bladder cancer is a different story.

Data from the first cohort of the phase 2 Trophy-U-01 trial showed Trodelvy shrank tumors in 27% of 113 metastatic urothelial cancer patients who had progressed after platinum chemo and checkpoint inhibitors. The response Trodelvy triggered lasted a median 5.9 months—and the drug completely eradicated signs of cancer in 6 (5%) of the treated patients.

RELATED: Astellas, Seattle Genetics’ Padcev bladder cancer trial stops early with 30% death risk reduction

However, that showing fell short of the 44% overall response rate—including 12% complete responses—that Seattle Genetics and Astellas’ anti-Nectin-4 ADC Padcev posted in its own phase 2 trial. In that study, dubbed EV-201, Padcev’s median duration of response also lasted longer, stretching into 7.6 months.

To put more pressure on Trodelvy, Padcev’s phase 3 EV-301 trial just stopped early after an interim analysis showed the drug cut the risk of death by an impressive 30% versus chemotherapy in the same third-line setting.

Although cross-trial comparisons can be problematic, industry watchers do it anyway to assess the competition. And after the Padcev trial halt this week, analysts pointed up the challenge for Immunomedics.

“We also believe Padcev’s overall survival benefit will raise the bar for its competitor Trodelvy,” SVB Leerink analyst Andrew Berens wrote in a Friday note to clients.

For Gilead, the Immunomedics deal marks CEO Daniel O’Day’s latest effort to turn the Big Biotech into an oncology force to be reckoned with. But even before the latest Padcev news, industry watchers were questioning whether Gilead overpaid.

For example, Bernstein analyst Ronny Gal figured third-line TNBC and bladder cancer only together represent about $ 1.5 billion in peak sales for Trodelvy. For Gilead to break even on the deal, Trodelvy needs to reach at least $ 4 billion at peak, meaning it’ll need to gin up an additional $ 2.5 billion in earlier lines of therapy and other tumor types, he said.

RELATED: Gilead needs ‘heroic’ Immunomedics revenues to get a return on $ 21B deal: analyst

Immunomedics has been trying to improve Trodelvy’s prospects by pairing it up with other drugs, too. When Gilead unveiled the $ 21 billion deal, Chief Medical Officer Merdad Parsey highlighted checkpoint inhibitors and PARP inhibitors as two promising combo options.

In a trial collaboration with Clovis Oncology, Trodelvy’s being tested in tandem with Rubraca in a phase 1/2 trial spanning multiple solid tumors, including TNBC, bladder cancer and ovarian cancer.

Plus, Roche is running a multiarm, phase 1/2 TNBC trial combining Tecentriq—currently the only PD-1/L1 inhibitor approved in TNBC—with different drugs, including Trodelvy in newly diagnosed PD-L1-positive patients. Interestingly, that study also includes Seattle Genetics’ experimental ADC ladiratuzumab vedotin (SGN-LIVIA), which Merck just splashed out $ 1.6 billion to license for pairing with Keytruda.

Trodelvy has its own Keytruda combo trials going, too. In bladder cancer, Immunomedics recently expanded Trophy-U-01 to include a Keytruda combo. In breast cancer, it plans to pit Trodelvy-plus-Keytruda against solo Trodelvy in a phase 2 test in previously untreated, metastatic TNBC. Another phase 2 will evaluate the same cocktail in HR-positive, HER2-negative disease.

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