Anybody with a more than passing interest in cancer has been transfixed the last few days by the news coming out of Chicago. The American Society of Clinical Oncology (ASCO) annual meeting has been especially newsy this year, chock full of important clinical trial news—some good, some bad, and some that you’d have to give a grade of ‘incomplete.’
I’ve been reading, writing, and editing a lot about cancer the past few days, but no one can absorb all the information coming out of ASCO. So today, I figured I’d wrap up some of the highlights from cancer drugmakers on the West Coast, with more to come from other parts of the country later this week.
Genentech. The South San Francisco-based unit of Roche dominated last year’s ASCO with data from its “supercharged” version of Herceptin, but it had to share the spotlight this year. Genentech is one of three companies racing ahead in the cancer immunotherapy field, along with Bristol-Myers Squibb and Merck. The latter two companies made the biggest splash with their antibodies that seek to inhibit PD-1, which disables a cloaking mechanism that tumors use to evade the immune system attack. Genentech’s antibody is designed to go after a slightly different target, PD-L1, which it hopes will make its drug less toxic—but that could be a tough case to make because the Merck and Bristol-Myers drugs both appeared to be quite tolerable in results presented at ASCO. Researchers were clearly psyched to report high rates of tumor shrinkage, and long-lasting remissions among patients in the early trials of these drugs. Now all three companies are sprinting to get these programs through all the necessary clinical trials required for FDA approval.
There was some non-immunotherapy news, too. Genentech reported some very impressive data with its new “son of Rituxan” drug obinutuzumab (GA101) for chronic lymphocytic leukemia. It also had some disappointment, too, as bevacizumab (Avastin) appeared to slow the progression of tumors in patients with glioblastoma, but the drug didn’t help the patients live longer.
Onyx Pharmaceuticals (NASDAQ: ONXX). The South San Francisco-based drugmaker had some modest good news to report for patients with thyroid cancer. Onyx’s sorafenib (Nexavar), which is already approved for kidney and liver cancer, showed it could keep tumors in check for a median time of 10.8 months in patients with thyroid cancer that had previously spread or resisted radiation therapy. That compared with 5.8 months for patients on the placebo. A total of 417 patients were enrolled in the study, known as Decision.
“The results were impressive, and we believe the leverage of follow-on indications with this product remains underappreciated by investors,” said Cory Kasimov, an analyst with JP Morgan, in a note to clients yesterday.
Yesterday, Onyx presented some data from a preliminary trial that showed carfilzomib (Kyprolis) was able to shrink tumors for about 91 percent of patients with newly diagnosed multiple myeloma, while the other 9 percent had stable disease. Updated data presented at ASCO was slightly better than results posted in an abstract, from an earlier data cut-off period. Onyx won FDA approval last year for the new drug for patients who have relapsed after getting other therapies, but it will capture a much bigger market opportunity if it can replicate these results in newly diagnosed patients. “The results, which were already “unprecedented” according to past investigators, continue to get better,” Kasimov wrote.
BioMarin Pharmaceutical (NASDAQ: BMRN). The San Rafael, CA-based company is best known for treating rare diseases, but it is gaining an increasing following for its work in cancer. It is one of several companies in the race to make drugs to inhibit poly ADP-ribose polymerase (PARP). The drug, called BMN 673, showed it could shrink tumors in 11 of 25 patients with breast and ovarian cancers that are very hard to treat, because they are driven by mutated forms of the BRCA genes. BioMarin is moving ahead with a once-daily dosing plan for a pivotal clinical trial in this tough-to-treat patient population. Click here to look at the full poster presentation.
Gilead Sciences. Foster City, CA-based Gilead is gaining more momentum as a cancer drug developer, behind some impressive data from its PI3kinase inhibitor, idelalisib. This drug, which Gilead acquired from Calistoga Pharmaceuticals in 2011, showed it could shrink tumors in 30 of 54 (56 percent) very sick, heavily pre-treated patients with chronic lymphocytic leukemia. The drug, an oral pill taken on its own without chemotherapy, was quite tolerable, with about 7 percent of patients dropping out of the study because of adverse events that might be treatment-related, researchers said. Gilead, as I described in a column in April, is putting its foot on the gas pedal in development. It presented data at ASCO for this drug as a treatment for slow-growing (indolent) non-Hodgkin’s lymphoma, and mantle cell lymphoma. It’s seeking to hit the market ahead of a competing product from Cambridge, MA-based Infinity Pharmaceuticals (NASDAQ: INFI).
Exelixis. The South San Francisco-based company (NASDAQ: EXEL) won FDA approval last year for cabozantinib (Cometriq) as a treatment for medullary thyroid cancer, but most people are more interested in its potential for treating other malignancies that are more common. The company presented some data to make its case in medullary thyroid, but analysts were thinking more about next year. Many are interested in Exelixis’s prospects for treating prostate cancer in a set of studies known as COMET. The Exelixis drug has shown ability in small studies to stop cancer from infiltrating the bones, where it becomes intensely painful as prostate cancer patients become terminal. “With Phase 3 data from the COMET studies anticipated next year, we were interested to gather some physician feedback. While still relatively sparse, what we did hear was generally optimistic,” said Kasimov, the JP Morgan analyst.
Sanofi. Remember BiPar Sciences, the Bay Area company with a PARP inhibitor that Sanofi acquired in 2009? The company released some eye-opening mid-stage clinical trial results at ASCO that year, and then failed to reproduce the results in a Phase III breast cancer trial in 2011. Sanofi refused to give up at the time, forging ahead with iniparib, the PARP inhibitor, in lung cancer. Then failed again, and the news this week is of a once-promising drug being tossed on the scrap heap. “You have to be humble in front of science,” Sanofi CEO Chris Viehbacher told Bloomberg News in an interview in Paris. The company is taking a $285 million write-off for its investment in iniparib.
Seattle Genetics. The Bothell, WA-based company (NASDAQ: SGEN) has had a lot of success the past couple years with brentuximab vedotin (Adcetris), a drug that combines the tumor-targeting capability of an antibody with a toxin that gives it extra tumor-killing kick. The company has licensed out its antibody-drug linking technology to a broad set of collaborators, who will plow a lot of money back into Seattle Genetics someday if they are successful.
This year at ASCO, Seattle Genetics started to show its collaborators are making progress. One study from Genentech found that 5 of 18 (27 percent) of very sick, heavily pre-treated patients with ovarian cancer had significant tumor shrinkage when they got a souped-up antibody using the Seattle Genetics technology. This “empowered antibody” was designed to hit a target called NaPi2b, which is commonly expressed on tumors of patients with ovarian and non-small-cell lung cancer. Side effects reported were mostly mild to moderate. Another Genentech antibody using the Seattle Genetics technology, aimed at a target called STEAP1, showed some antitumor capability in very sick patients.
Dendreon. There were no earth-shaking announcements from Dendreon, the pioneer of immunotherapy, at this ASCO meeting dominated by other aspiring immunotherapy companies. But Dendreon (NASDAQ: DNDN) did present some data that suggest patients who got its immune-booster for prostate cancer, when they still had disease under control by existing hormone deprivation therapies, were able to have their immune systems primed by infusions with sipuleucel-T (Provenge). That’s a bigger population of patients than Dendreon currently targets, those with disease that no longer responds to hormone-deprivation (aka chemical castration.) Another small study looked at whether the Dendreon immune-booster could be given alongside, or after, a competing treatment called abiraterone acetate (Zytiga) from Johnson & Johnson.
“These studies help us understand how Provenge may be combined or sequenced with other advanced prostate cancer treatments,” said Mark Frohlich, Dendreon’s chief medical officer, in a statement.
Oncothyreon. The Seattle-based company (NASDAQ: ONTY) has had a rough few months, as its partner Merck Serono reported on the failure of the Stimuvax immunotherapy in a 1,500 patient lung cancer study last December. Oncothyreon’s next program in line, a PI3 kinase inhibitor, hasn’t yet shown any positive data from mid-stage trials, and it’s in a fiercely competitive field. CEO Bob Kirkman has said the company is still planning to develop a next-generation immunotherapy designed to be better than Stimuvax, but that ultimate decision will depend in part on what Merck Serono does next in development with the original drug.
Halozyme Therapeutics (NASDAQ: HALO). The San Diego-based company has dared to develop a drug against advanced pancreatic cancer, where many other drugs have foundered. The company is developing an experimental biologic drug called PEGPH20, in combination with a standard chemo drug, gemcitabine. The Halozyme drug is supposed to eat away at a protective matrix made up of hyaluronan, which encases pancreatic tumors, and makes it hard for the chemotherapy to sink deeply into the tumor and kill the fast-dividing cancer cells.
The small study was designed to start with super-small doses and ramp up gradually to evaluate side effects at escalating doses. Once researchers got to doses that might actually be effective in very sick, Stage IV pancreatic cancer patients, they saw 33 percent of the 21 evaluable patients had significant tumor shrinkage. The side effects were mostly mild to moderate muscle spasms, muscle pain, and joint pain. Biopsies from patients’ tumors also showed that those with a high amount of hyaluronan in their tumors had a better chance of benefitting from the Halozyme drug. Based on the results, Halozyme said it has selected a dose to go into mid-stage clinical trials that will be designed to assess effectiveness.
“Pancreatic cancer is one of the most challenging cancers to treat. We are encouraged by these early stage clinical data, and look forward to further testing the potential of PEGPH20 in randomized trials in combination with the most active regimens available for patients today” said Sunil Hingorani, a researcher at the Fred Hutchinson Cancer Research Center, in a Halozyme statement.