Scientist-Patient and Family Shoot for a Cancer Cure (2)

Allan Basbaum became obsessed with the hope of getting Iniparib to his wife and other cancer patients. He presented the case repeatedly to venture capitalists to raise money for the startup. His talks stressed how the new drug inhibited cancer cell survival. The drug blocked a few proteins, including the PARP enzyme. And, while his wife coped with her cancer, Dr. Basbaum became mired in venture capital clichés: “Was this a ‘must-have’ drug?” “What’s the revenue model?” “Will insurance pay for the drugs?” “Cash is king. Do you have it?” “The model needs to be profitable?” No answer pleased. The money men around the table kept their eyes on their Blackberries. The startup was going down. Carol Basbaum’s tumors were not.

Finally, Kirk Raab (past Genetech CEO) was asked to be the chairman of the BiPar board. For years, Raab had been sharing his experience with new entrepreneurs. He revamped and shortened Allan Basbaum’s pitch; presenting the drug as a leading PARP inhibitor. By 2004, the venture dollars poured in.

Nonetheless, hope for the Basbaums dimmed as time passed and then disappeared; the phase I trials of Iniparib in humans didn’t begin until 2006. By 2008, phase II trials to treat “triple negative” breast cancers helped some patients with no other options.

With the excitement around the phase II results, Sanofi Inc. bought BiPar to further develop this first “PARP” inhibitor, Iniparib. Sanofi became the PARP inhibitor leader and quickly moved to carry out phase III trials in patients with lung or “triple negative” breast cancers. In the meantime scientists at the Mayo clinic and Abbott labs cautioned that when tested on cultured cells, Iniparib was not as specific or powerful as other PARP inhibitors.

Ultimately, in what seemed like a series of explosions, Sanofi’s phase III trials of Iniparib for lung cancer and breast cancer “failed.” Why they didn’t test Iniparib in patients who inherited BRCA mutations or mutations in other DNA repair enzymes is not clear. Did they think it wasn’t a specific PARP inhibitor and went for a broader effect? By 2013, Sanofi gave up on Iniparib and disowned it. Iniparib is now an orphan drug in need of adoption.

Opinions about Iniparib come in different shades of “it’s a failure” to “it works.” But one thing is for sure, no one is sure of why Sanofi’s trials “failed.” Was Iniparib tested on the wrong patients? Or was the drug just not good enough? The subgroup of patients and their doctors that benefited from Iniparib, as described in a recent report of the phase III trial of Iniparib in breast cancer argue for its value. Those patients who were helped may hold the answers.

When Sanofi dropped their PARP inhibitor, dominos fell. Some companies halted their PARP inhibitor programs. Others slowed. But the story didn’t end there. AstraZeneca, Inc. forged on. Their researchers, who learned from Sanofi’s trials and tribulations, carefully selected patients likely to respond – those with BRCA mutations. With this persistence and the FDA’s “fast track” approval, we now have a second chance to test drive PARP inhibitors with Olaparib. Dr. Carol Basbaum, the committed researcher and BRCA1 mutation carrier who tried many times to overcome her cancer, would have qualified for this drug.

Near the end of her life, Basbaum’s doctor said “If I were you, I’d stop working to enjoy….” Carol, who rarely raised her voice, interrupted with, “That’s because you probably prefer traveling somewhere exotic to being in a lab. But I don’t.” Such blunt words, recalled by her husband, from this basic research “queen’’ resonate with her fellow scientists and patients. Her endurance foreshadows the energy, strength, and years of commitment needed to make progress in cancer research.

This piece was originally published on Signature.