Genentech's Tecentriq Misses Mark in Urothelial Cancer Trial

Missed endpoint

Although checkpoint inhibitors like Genentech’s Tecentriq (atezolizumab) are great drugs, they clearly don’t work in every indication. Genentech, a Roche company, announced that its Phase III IMvigor010 trial of Tecentriq as a post-surgery monotherapy didn’t hit its primary endpoint in muscle-invasive urothelial cancer (MIUC).

The primary endpoint was disease-free survival (DFS). The safety signals were consistent with the known safety profile.

“Reducing the risk that muscle-invasive urothelial cancer will recur after surgery is very difficult, and we are disappointed that we were not able to significantly prolong disease-free survival,” said Levi Garraway, Genentech’s chief medical officer and head of Global Product Development. “We remain committed to exploring the potential benefits of immunotherapy for more people with early cancers.”

MIUC is a type of bladder cancer that has spread into the muscle wall of the bladder, ureter, or renal pelvis. About a quarter of newly diagnosed bladder cancer patients are diagnosed with muscle-invasive disease, which typically has a worse prognosis than non-MIUC bladder cancers.

IMvigor010 is a global Phase III trial. It analyzed 809 people with MIUC who are at high risk of recurrence after surgery.

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Genentech is continuing studies in early and advanced bladder cancer and Tecentriq, as well as numerous ongoing and planned Phase III trials in other cancers, including genitourinary, skin, breast, gastrointestinal, gynecological, and head and neck cancers. These studies evaluate Tecentriq as a monotherapy and in combination with other drugs.

Yesterday, the company announced topline results from its pivotal Part 2 of its FIREFISH trial of risdiplam in infants aged 1-7 months with Type 1 spinal muscular atrophy (SMA). SMA is a severe, inherited neuromuscular disease causing muscle atrophy. It affects about one in 11,000 babies and is the most common genetic cause of infant mortality, leading to progressive loss of nerve cells in the spinal cord.

Risdiplam is a survival motor neuron-2 (SMN-2 splicing modifier. It is engineered to increase and sustain SMN protein levels throughout the central nervous system and peripheral tissues. Genentech developed the drug in collaboration with the SMA Foundation and PTC Therapeutics.

Risdiplam, if approved, is projected to bring in $2 billion in annual sales.

Tecentriq, on the other hand, is indicated to treat advanced urothelial carcinoma, metastatic non-small cell lung cancer, extensive-stage small cell lung cancer, and in combination treatment of metastatic triple-negative breast cancer. The leaders in the lung cancer checkpoint inhibitor market are Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo. Genentech’s Tecentriq sales are about 10% of Merck’s Keytruda sales. Tecentriq has been projected to bring in about $2.18 billion in sales this year, while Merck’s Keytruda is projected to bring in $11.5 billion. Bristol-Myers Squibb’s Opdivo is projected to have $7.5 billion in sales for 2020.

Meanwhile, BeiGene recently reported positive data from its own checkpoint inhibitor, tislelizumab in combination with two chemotherapy drugs in squamous non-small cell lung cancer (NSCLC). It met the primary endpoint of improved progression-free survival (PFS) in its clinical trial, and if approved, would likely provide a big competitor to Merck’s Keytruda in the China market for lung cancer.

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