The herds who attended the American Society of Clinical Oncology have now gone home after a frenzied few days of absorbing what’s new in cancer R&D. Yesterday, I wrapped up some of the big news from cancer drugmakers on the West Coast, and now I’m attempting to hit the highlights of companies from the other innovation hubs in the Xconomy network.
There’s a lot to digest here, so without any further windup, here’s what caught my eye from our various locales:
Tesaro (NASDAQ: TSRO): The Waltham, MA-based cancer drug developer raised more than $100 million in venture capital in 2011, and then went out and pulled in more than $80 million a year later in an IPO, largely on speculation that it had a seasoned management team of cancer drug developers who could do it again. This year at ASCO, the company started to show some very preliminary clinical trial data, and investors went all gaga for it.
Tesaro’s lead compound is niraparib, one of several drugs designed to fight cancer by inhibiting a target called PARP. The company made a minor announcement on Monday at ASCO, saying it had struck an agreement with a European physician network to conduct a pivotal study of 360 patients with ovarian cancer. Yesterday, Tesaro presented some preliminary data that said three out of four patients on an optimal dose of niraparib, who had a chemotherapy-sensitive form of ovarian cancer, had significant tumor shrinkage. Half of the patients with chemo-sensitive ovarian cancer and mutations to their BRCA genes (five out of 10 patients) had significant tumor shrinkage, even when including patients who got lower doses. Side effects consisted mostly of anemia, fatigue, and nausea, which were mild to moderate in severity. The drug appeared to keep tumors in check for more than a year for patients who have mutations to the BRCA genes that raise cancer risk, and for patients without those genetic mutations, the company said.
There are other tough competitors in the PARP field—notably San Rafael, CA-based BioMarin Pharmaceutical, London-based AstraZeneca, and North Chicago, IL-based AbbVie—but one key rival dropped out of the race this week. Paris-based Sanofi said it was taking a $285 million write-off on its PARP inhibitor after it failed in a pivotal lung cancer study. Investors apparently like Tesaro’s chances of standing out in the crowd. Shares of Tesaro shot up from $34.21 on Friday, to briefly eclipse $50 a share on Tuesday.
Synta Pharmaceuticals (NASDAQ: SNTA): The Lexington, MA-based cancer drugmaker saw its shares drop the most in four years on Monday after Synta reported that survival results for its lung cancer drug fell short of investor expectations, according to a report by Bloomberg News. The company said patients lived a median time of 9.8 months on a combination of its ganetespib drug and standard docetaxel chemotherapy, compared with 7.4 months for those who got docetaxel alone, in a trial of 252 patients presented at ASCO. The product is designed to inhibit a protein called Hsp90, which scientists say serves as a chaperone that helps cancer cells grow and proliferate.
Infinity Pharmaceuticals (NASDAQ: INFI): The Cambridge, MA-based cancer drug developer had a see-saw ride at ASCO this year. Shares tanked on Monday, then bounced back on Tuesday. Infinity’s most important product is IPI-145, an inhibitor of the PI3 kinase biological target, in particular its delta and gamma variations. Gilead Sciences rolled out some impressive results from clinical trials of its competing PI3k-delta inhibitor, idelalisib, which is moving ahead in a series of pivotal clinical trials for blood cancers. On Monday, Infinity said that 13 of 19 patients with slow-growing (indolent) non-Hodgkin’s lymphoma (68 percent) had significant tumor shrinkage on its drug, with three complete responses and 10 partial responses. Another study showed that 12 of 22 patients with relapsed forms of chronic lymphocytic leukemia (55 percent) had tumor shrinkage. There was some moderate to severe liver toxicity observed in patients on the Infinity drug, which was seen in 21 of 68 lymphoma patients, researchers said.
By Tuesday, the storm appeared to have passed. Infinity stock fell from Friday’s close of $26.95 to $16.41 at the end of Monday, the first day of ASCO. But on Tuesday, it regained some of the value it had lost, climbing back over $20. Much of the roller-coaster stock action was apparently based on investor fears that the Infinity drug was more toxic than previously believed, and based on some comparisons seen in other studies. “Yesterday’s concerns with IPI-145’s safety profile were overdone, and that at this stage it appears to be in line with other agents in development – a point that study investigators have been highlighting all weekend,” said JP Morgan analyst Cory Kasimov, in a note to clients yesterday.
ImmunoGen (NASDAQ: IMGN): The Waltham, MA-based biotech has had a good year, as it stands to collect royalties on Genentech’s next big thing—the “supercharged” version of its targeted breast cancer drug, trastuzumab emtansine (Kadcyla). But it has long yearned to show investors that it can make more potent antibodies for cancer on its own, without leaning on partners to do most of the heavy lifting. Preliminary results from 18 patients who got a variety of escalating doses didn’t say much about how effective ImmunoGen’s latest drug candidate, IMGN853, really is. The company cited three cases of significant tumor shrinkage on patients who got moderate to high doses of its drug, and noted that all three responders had tumors that had a lot of FR alpha biologic targets on them—the target that ImmunoGen’s drug is supposed to hit. The drug is now advancing in further development, and ImmunoGen plans to seek out FR alpha over-expressers with a variety of different tumor types, including ovarian cancer, non-small cell lung adenocarcinoma, and endometrial cancer.
Bristol-Myers Squibb (NYSE: BMY). New York-based Bristol-Myers garnered most of the big headlines and excitement this year at ASCO with its new antibody that unleashes the power of the immune system to fight tumors. This drug, nivolumab, is designed to block the PD-1 biological target, which acts like a cloaking mechanism to help tumors evade the immune system. Bristol-Myers generated lots of buzz with its PD-1 antibody at last year’s ASCO, and it continued this year, because the drug is showing an ability to shrink tumors for a wide variety of tumor types, and an ability to generate long-lasting responses for patients. One study of 53 melanoma patients, published in the New England Journal of Medicine, showed that when Bristol combined nivolumab with another immunotherapy—ipilimumab (Yervoy)—it was able to shrink tumors by more than 80 percent for a majority (53 percent) of the patients. Doctors were so pumped up about the results that they were increasingly talking in grand terms about a new coming era of immunotherapy. While there were some cautionary voices saying that patients need to be followed up longer and results need to be reproduced, the breathless voices tended to be heard more loudly.
“During Q and A, a doctor asked why a Phase 3 was even necessary for this regimen….that question I think describes sentiment here at ASCO around this regimen better than I can,” said Mark Schoenebaum, an analyst with ISI Group, in a note to clients on Sunday.
Merck (NYSE: MRK): The Whitehouse Station, NJ-based drug giant (NYSE: MRK) competed with Bristol-Myers for the most buzz at this year’s ASCO, with its own antibody directed at PD-1, which it calls lambrolizumab. This drug, in a study of 135 advanced melanoma patients, showed that when patients got a high dose every two weeks, more than half (52 percent) had significant tumor shrinkage. There was no control group in this study for a good comparison, but researchers know from past studies that about 5 percent of patients with this prognosis tend to respond to another round of chemotherapy.
What might have been more exciting than the response rate was how long the new Merck drug appeared to keep tumors down. Researchers still don’t know how long the responses will last, but the patients have been followed for a median time of 11 months, and not enough have seen their disease worsen to provide a valid estimate of how long the drug works.
“These are clearly much more sustained responses than are seen with targeted agents or chemotherapy. That’s what makes this class such an impressive class,” said Eric Rubin, Merck’s vice president for oncology clinical development. Merck’s results, along with some other data from Genentech/Roche against a related target called PD-L1, made immunotherapy the dominant story of the meeting. All three companies are racing ahead to design the next phases of studies required for these products to win FDA approval.
Biodesix: The Boulder, CO-based maker of molecular diagnostic tests got some attention with results from a 285-patient, prospective study called Prose. [Corrected 11:30 am PT: An earlier version said the trial had 245 patients.] This trial was designed to help physicians figure out the best treatment strategy after first-line treatment, usually chemotherapy, has failed. The question at that point often becomes whether a patient should take a second round of chemo, or whether he or she should try a targeted agent, Roche/Genentech’s erlotinib (Tarceva). The Biodesix blood test, which looks for certain proteins, found that when it classified patients as “VeriStrat Poor” they lived longer on chemo than on the targeted drug, and when they were classified as “VeriStrat Good” they had similar survival outcomes on the different treatments.
Jack West, an oncologist at Swedish Medical Center in Seattle who covered the meeting extensively on Twitter, said he was unimpressed with the VeriStrat data. While the company said it hopes the data will encourage more physicians to use the test, West said the Biodesix data presentation lacked important information on tumor shrinkage rates, and the time patients were able to keep their tumors from spreading—omissions that he called “puzzling.” Plus, lung cancer patients who have a normal form of a gene for a protein called EGFR would always, logically, get chemotherapy before a targeted drug like erlotinib, meaning he sees little need for such a test.
Clovis Oncology (NASDAQ: CLVS): Clovis’ stock was worth $36.58 a share on Friday before ASCO started, and it was worth $74.59 by the end of the conference on Tuesday. The bull run was based on what JP Morgan’s Kasimov called “extremely impressive” data for the Boulder, CO-based company’s lung cancer drug, CO-1686. The drug is designed to treat people with mutant forms of the epidermal growth factor receptor (EGFR) including those with another mutation known as T790M that enables tumors to develop resistance to other EGFR-targeted drugs. Four of six patients with the T790M resistance mutation (67 percent) had significant tumor shrinkage, at lower doses than patients will likely get in subsequent clinical trials designed to measure effectiveness. This story resonated because doctors have been looking for years to find better ways to treat patients after they develop resistance to erlotinib (Tarceva) or gefitinib (Iressa).
A total of 42 patients had gotten the drug in one of its various doses through May, and 26 of them (62 percent) had some kind of drug-related side effect, Clovis said. Fatigue, nausea, diarrhea and muscle spasms were the most common side effects, although most were mild to moderate in severity, and they didn’t cause any patients to drop out of the study. There are no FDA approved drugs for the group of patients with T790M resistance mutations.
Array Biopharma (NASDAQ: ARRY): Array is one of the companies that had some data to tout at the ASCO meeting, but clearly got overshadowed. The Boulder, CO-based company reported that selumetinib, its drug for specifically inhibiting a target called MEK, was able to keep tumors from spreading a median time of 15.9 weeks for patients with a rare malignancy called uveal melanoma—a rare type of skin cancer that invades the eye. That result compared with 7 weeks for those on chemotherapy. The results—billed as the first benefits for patients with advanced uveal melanoma—are enough for Array’s partner, AstraZeneca, to move into the third and final phase of clinical trials normally required for FDA approval. Array has another MEK inhibitor it is developing in a partnership with Novartis, and analysts said they were encouraged not just by the Array results, but the fact that a competing MEK drug from GlaxoSmithKline won FDA approval before ASCO as a first-in-class molecule.
“With planned multiple Phase 3 initiations from ARRY’s partnered two MEK programs (e.g., selumetinib with AstraZeneca and MEK-162 with Novartis) in 2013, we view progress in partnered programs will likely drive valuation upside,” said Eun Yang, an analyst with Jefferies & Co., in a note to clients on June 2.
Array, however, showed that it’s hungry for more investor cash to get through those next steps, which cast a bit of a damper on its stock. The company said it filed paperwork with regulators to borrow up to $100 million, in a debt offering that could be converted into stock. Array shares fell 8 percent Tuesday.
Castle Biosciences, a Friendswood, TX-based diagnostics company, presented data at ASCO from a test called DecisionDx-Melanoma that looks at how 31 different genes are expressed in Stage I and Stage II melanoma patients, in an effort to predict whether they have the kind of disease that’s likely to spread later to other organs. Researchers looked at tumor biopsy samples, classified them as either high-risk (Class 2) or low-risk (Class 1), and then looked at 5-year follow-up records from the patients. The study found that the patients classified as high-risk ended up having a 72 percent chance of having their tumors spread. While some newer diagnostic tests are designed to cut back on overly aggressive treatment, this is a result that suggests physicians and patients might want to get more aggressive with melanoma patients who previously might have gotten the wait-and-see approach.
“This suggests non-metastatic Class 2 patients are at a very high risk and should be considered for aggressive surveillance and therapeutic interventions that are routinely given to Stage III patients,” Pedram Gerami, an associate professor of dermatology at Northwestern University, and a study co-author, said in a Castle statement.