ASCO 2014: Making and Breaking Cancer Drugs

As oncology has become the hottest space within pharmaceuticals and biotech, the annual American Society of Clinical Oncology (ASCO) is pretty much now the Super Bowl for companies in this space. Meetings like ASCO certainly do lead to companies releasing important data on pipeline candidates, as well as often hosting meetings/presentation to explain their pipelines and development strategies in more details. It's worth remembering, though, that a lot of what is presented is early stage, includes limited number of patients, and often focuses on metrics like response rate that are ultimately less significant than metrics like overall survival.

All of that said, with the abstracts for the meeting now out, it looks like incrementally good news for Roche and Merck , and encouraging news for AstraZeneca and Lilly . For Bristol-Myers Squibb the reaction is likely to be far less positive from investors, though it is early to make any sweeping pronouncements.

Roche comes through
For Roche the news was pretty positive. The company's PD-L1 drug showed a 50% response rate in bladder cancer. More than 70% of the patients had received two or more prior treatments and the historical ORR rates in those patients is typically less than half of what this study has shown. If these results hold up through pivotal testing, this could be an indication worth $2 billion or more in revenue.

Roche also presented impressive data in a combination study of Rituxan and the Bcl-2 inhibitor known as GDC-0199 and ABT-199. As that latter name might have suggested, this drug was partnered-in from AbbVie and in refractory CLL the combo showed a complete response rate of 39%-an impressive result that compares quite well to the Johnson & Johnson/Pharmacyclics drug Imbruvica. Importantly, the MRD negative rate of 28% suggests a a potential cure of CLL in a meaningful number of patients.

Roche also presented early stage data on its anti-CSF1R drug, which has so far shown a partial response in seven of 10 patients treated for PVNS.

Merck is going to be a player
Merck isn't presently all that much this year in terms of breadth, but the quality of lead drug MK-3475 (an anti PD-1 antibody) appears to be significant. As a first-line treatment for non-small cell lung cancer, the drug produced a 36% overall response rate and a 67% response rate in PD-L1-positive patients. That's on par with Bristol-Myers' nivolumab, suggesting that MK-3475 is a valid and competitive drug at this point.

AstraZeneca scores a few points
AstraZeneca's ASCO abstracts didn't look like home runs, but they did get a few solid hits in this year. The company's PD-L1 monotherapy candidate looks effective in terms of response rates across a variety of tumor types. Potentially even more important is the good early signs regarding tolerability of the combination of the anti-PD-L1 drug and tremilimumab in comparison to combo therapies of nivolumab and Yervoy. AstraZeneca is also presenting data that suggest AZN-9291 offers similar efficacy in second-line lung cancer to Clovis' CO-1686.

Mixed news for Lilly
Lilly's major ASCO abstracts were a little more mixed, but positive on balance relative to expectations. The data on necitumumab in lung cancer wasn't very impressive (a 1.6-month benefit to overall survival), but there was no particular expectation that it would be. On the other hand, the results from CDK 4/6 inhibitor abemaciclib (LY2835219) looked pretty good. In a heavily pre-treated group of NSCLC patients, 51% showed complete/partial response or stable disease.

Disappointment for Bristol-Myers, but only to a point
That investors seem to be so disappointed with Bristol-Myers really speaks more to how expectations have grown for this company's immuno-oncology program than the actual quality of the data. The data on the Yervoy/nivolumab combo were disappointing - a 22% overall response rate and pretty high toxicity (three treatment deaths and 48% grade 3-4 events), but this is early stage data and the response rates may improve. On the other hand, more mature data in a monotherapy study of nivo in lung cancer showed a two-year overall survival rate of 45% at the 3mg/kg dose - an exceptional result for a disease that typically has a 15% 5-year survival rate. It's also well worth noting that the data on the nivo/Yervoy combo in renal cancer were quite good, with response rates above 40%.

The bottom line
This year's Big Pharma ASCO abstracts make at least two things quite clear. First, investors have gone absolutely head-over-heels for immuno-therapy. Second, in many cases the data from these drugs supports a lot of that optimism. It really does look like PD-1/PD-L1 antibodies are going to reset expectations for response and survival rates in many cancer types and fuel the next round of multibillion-dollar drugs for Big Pharma. Competition is going to be fierce, though, putting a premium on clean data (high efficacy and high tolerabilty is the ideal), skillful clinical management, and good marketing efforts.