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: [[ticker:MRK]]): The Whitehouse Station, NJ-based drug giant (NYSE: [[ticker: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.
Boulder/Denver
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: [[ticker: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: [[ticker: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.
Texas
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.
