There are few scarier diseases than cancer and few cancer types that stack the odds more against the patient than lung cancer. I can somewhat speak from the heart on this, as I lost my mother to non-small-cell lung cancer three years ago and understand what a difficult disease it is to treat. There's little I wish for more than a cure for this disease.
Alas, lung cancer treatments often swing for the fences, but few treatments actually wind up hitting a home run. According to the American Cancer Society, it's estimated that 228,190 people will be diagnosed with some form of lung of bronchus cancer just this year. Based on the latest round of data collected between 2002 and 2008, only 17% of those diagnosed will survive five years or longer. That is an improvement from 12% in 1975-1977, but it's quite a minimal improvement over three decades, all things considered. Worse yet, lung cancer is responsible for more deaths, by far, than the next most-deadly cancer.
With that in mind, I'd like to take a closer look at five of the more exciting treatments currently being developed to treat lung cancer. I think a deeper dive into these experimental treatments is important for two reasons. One is obviously improving a patient's quality of life. The ultimate goal, of course, is to find a cure, but for now anything that improves progression-free survival or overall survival while boosting quality of life is a step in the right direction. Second, it could represent an intriguing investment opportunity for the companies behind these experimental therapies.
So let's have a look at some of lung cancer's most intriguing clinical drugs, shall we?
Novartis (NYSE:NVS): LDK378
Perhaps no clinical-stage therapy is more exciting than Novartis' LDK378 for the treatment of ALK-positive non-small-cell lung cancer, or NSCLC. This compound is one of just a handful of experimental drugs to possess the breakthrough therapy designation because of its markedly superior early stage results, as compared to the current standard of therapy. It's also unique in that it targets the ALK mutation, which is present in about 3% to 8% of all NSCLC patients, but more often younger people and non-smokers.
In June, Novartis released data from its 114-patient phase 1 study, and they were nothing short of phenomenal. The overall response rate was 60% for the higher dosage (750 mg a day), and it clearly showed a marked response in patients who had shown cancer progression while on Pfizer's Xalkori. Because of its breakthrough designation, once it proves that the drug is safe, Novartis can use the efficacy of this phase 1 data as the basis for a new drug application filing in early 2014. I have four more drugs to tout, but if you're going to take one drug away from this analysis that you need to follow, LDK378 is it!
Peregrine Pharmaceuticals (NASDAQ: PPHM): bavituximab
Mr. Toad's Wild Ride wouldn't even do justice to the seat-jostling ride Peregrine shareholders have been on over the past year. At first, bavituximab's clinical data knocked Wall Street out of the park and its share price soared. Then, weeks later, Peregrine's management said not to trust the data and that it would need to be examined further -- the stock cratered. Finally, months later, everything was well again and top-line data confirmed that bavituximab could be the real deal.
Bavituximab was developed as a second-line treatment for refractory NSCLC, and it was tested in a mid-stage trial on 121 patients. Based on the results, bavituximab's pooled data (i.e., combining the 1 mg and 3 mg dosing cohorts) demonstrated a better than doubling in median overall survival to 12.1 months from 5.6 months for the placebo while delivering a 40% bump in progression-free survival to 4.2 months and doubling the overall response rate to 16.5% from 7.9%. These are really exciting numbers, but following the "did they or didn't they" circus stirred up last year, I think investors really want to see how bavituximab fares in a bigger late-stage trial before they commit wholeheartedly. Let's keep in mind that lung cancer drugs from small biotech companies have a very poor track record in late-stage studies, but it's also hard to overlook highly statistically significant improvement like this.
Bristol-Myers Squibb (NYSE:BMY): nivolumab
Nivolumab represents another interesting class of experimental therapies, as it's an ant-PD-1 inhibitor, also known as programmed death-1. Essentially, nivolumab is an immunotherapy that prevents a protein, PD-1, from binding with PD-L1 and PD-L2. This protein is understood to be a big reason cancer cells go undetected by our immune system. With this protein blocked, our body's autoimmune response to fight targeted cancers such as lung cancer, advanced melanoma, and renal cell cancer is improved.
Although the buzz has overwhelmingly been over nivolumab's overall response rates in treating melanoma, the experimental immunotherapy has also turned in some impressive results in treating metastatic NSCLC. In a 129-patient trial announced earlier this year, the 3 mg dosing cohort demonstrated 20% to 25% overall response rates in squamous- and non-squamous-cell lung cancer. Even more impressive, overall survival for patients at two years was 14%. I know some of you might be scratching your head, since I mentioned a five-year survival of 17%, but understand that the five-year survival rates is inclusive of all stages of cancer. Nivolumab is strictly being given to metastatic (stage 4) cancer patients who've tried, in many cases, three or four different therapies, and it's prolonging their life quite a bit. It's certainly an eye-opening and intriguing therapy worth watching.
Merck (NYSE:MRK): lambrolizumab
We can't mention nivolumab without mentioning its competing PD-1 drug, which is raising just as many eyebrows: Merck's lambrolizumab. Like nivolumab, lambrolizumab works by enhancing the body's own autoimmune system to fight disease; and like nivolumab, it was very effective at delivering an overall response in advanced melanoma.
Now here's the tricky part: The only concrete lambrolizumab data we have at the moment is its advanced melanoma trial, where it delivered an overall response rate of 52% at the optimal dosage -- which by itself is remarkable. In this quarter, Merck is expected to begin enrolling a late-stage study of lambrolizumab in NSCLC, but we won't have those results until probably the latter half of next year. All we really have to go on is the correlation of success between lambrolizumab and nivolumab in advanced melanoma, since they work along the same pathway and just hope that lambrolizumab translates into a successful treatment for NSCLC. Like nivolumab, lambrolizumab has a ton of potential, and it also possesses the breakthrough therapy designation. I'd strongly suggest keeping an eye on its development in treating NSCLC into next year.
Clovis Oncology (NASDAQ:CLVS): CO-1686
Last, but certainly not least, is Clovis Oncology's EGFR-mutant NSCLC treatment. Now I've made no qualms that I'm not supportive of Clovis' current $2.25 billion market valuation, given its young and non-diverse pipeline, but I nonetheless must respect that CO-1686 could offer an intriguing targeted therapy if it achieves strong mid- and late-stage results.
Currently, CO-1686 is still in the early stages of its development -- assessing the proper dosage and establishing overall drug safety. What is intriguing, though, is that the drug demonstrated a partial overall response in three of four patients with the dominant resistance mutation T790M. Obviously, I'd like to see a bigger patient pool as well before I get too excited, but CO-1686 could ultimately wind up having a big effect on targeted NSCLC patients just like LDK-378 targets ALK-positive NSCLC patients. I can't say I'm a fan at all of the valuation here, but the therapy definitely bears watching.