This account is pending registration confirmation. Please click on the link within the confirmation email previously sent you to complete registration.
Need a new registration confirmation email? Click here
Stocks Under $10 with 50-100% upside potential - 14 days FREE!

The Endocyte Bear Thesis: Why March Will be a Bad Month

Editor's note: March is shaping up to be an important month for Endocyte and its experimental cancer drug vintafolide. Sometime during the month, Endocyte will be announcing top-line results from a phase II study of vintafolide in non-small cell lung cancer. From March 17-20, European regulators will be meeting and are expected to issue an opinion on whether or not to approve vintafolide for the treatment of advanced ovarian cancer.

The following column was written by a healthcare fund investment manager who is short Endocyte. His firm doesn't allow him to be identified by name in the media.

NEW YORK (TheStreet) -- I believe Endocyte (ECYT) is a short for two primary reasons. 1) European regulators are unlikely to grant conditional marketing approval to the company's experimental cancer drug vintafolide for the treatment of ovarian cancer; and 2) an ongoing phase II study of vintafolide in non-small cell lung cancer is likely to fail.

Every stock has a bull and bear thesis. Smart investors weigh the potential benefits and risks of a stock before reaching a conclusion. In this article, I'm going to explain the risks associated with Endocyte and its lead compound vintafolide because I believe it's a more compelling argument. I trust you'll seek out an opposing bullish view on the stock elsewhere before reaching your own conclusion. [Editor's note: TheStreet contributor David Sobek is bullish on Endocyte's chance for European approval. Read his take here.]

Endocyte refers to its technology platform as small molecule drug conjugates (SMDCs), which link a chemotherapy drug payload to a targeting ligand. The ligand is designed to bind to a specific receptor found on cancer cells and then release the chemotherapy payload to kill those cells.

The company's lead SMDC is vintafolide, which consists of folate (vitamin B9) linked to the chemotherapy drug vinblastine. Ovarian and lung cancer cells have an over-abundance of folate receptors on the surface of their cells, so Endocyte believes vintafolide binds to these folate receptors and delivers its chemotherapy payload while leaving normal cells intact. [Endocyte uses a companion diagnostic test to identify patients with tumors that over-express folate receptor.]

Endocyte conducted a phase II study of vintafolide in patients with platinum refractory ovarian cancer. Results from this study were submitted to European regulators seeking conditional approval. European drug reviewers and Endocyte participated in an oral explanation (hearing) for vintafolide last week, which should lead to an opinion being announced as early as March 17-20.

As I said above, I predict European regulators won't recommend the approval of vintafolide for ovarian cancer.

The phase II "Precedent" study enrolled 149 patients with platinum-resistant ovarian cancer. The patients were randomized 2:1 to receive vintafolide plus PLD (Doxil) or PLD (Doxil) alone.

In the intent-to--treat patient population, vintafolide+PLD delayed the median time to tumor growth or death (progression-free survival, or PFS) by 5 months compared to 2.7 months for PLD alone. The result was statistically significant.

Endocyte also looked retrospectively at a subset of 38 patients from the study with ovarian cancer that had 100% expression of the folate receptor. In these patients, vintafolide+PLD demonstrated a median PFS of 5.5 months compared to 1.5 months for PLD alone -- a four-month benefit that was also statistically significant. Overall, treatment with vintafolide reduced the risk of tumor progression by 62% in these 100% folate-receptor ovarian cancer patients.

All the data reported by Endocyte are based on assessments made by investigators who participate in the phase II study. When the results were analyzed independently, vintafolide's PFS benefit narrowed and in some cases lost statistically significant. This is important because regulators usually give more weight to independent analysis of study data.

European regulators are being asked to approve vintafolide based on this PFS benefit, but what really matters is overall survival. In the phase II study, vintafolide trended toward worsening overall survival. The hazard ratio was 1.1 meaning vintafolide patients had a 10% greater risk of dying compared to patients treated with PLD -- although this trend was not statistically significant.

In fact, the entire vintafolide benefit Endocyte observed in the phase II Precedent study is readily explained by the fact that vintafolide-treated patients in this unblinded study received significantly more PLD than the control patients (162.5mg vs. 100mg.) The baseline characteristics of the control patients were also better than patients in the vintafolide arm.

The question faced by European regulators is whether to approve today vintafolide for the treatment of platinum refractory ovarian cancer based on data from a 38-patient, post-hoc sub-group in which a four-month PFS benefit was coupled with a trend towards worse overall survival. Moreover, increased Doxil exposure -- a drug known to be effective in this population -- explains the PFS benefit observed more than any effect of vintafolide.

Endocyte is running a larger phase III study of vintafolide in ovarian cancer right now, aiming to replicate and confirm the results seen in the phase II study. My bet is European regulators decide the phase II data aren't sufficient to approve vintafolide right now and will instead wait for results from the phase III study.

Let's move on to the second part of the bear thesis: Vintafolide's lung cancer study. Endocyte's partner Merck (MRK) is expected to announce results from this study in March.

The phase II study enrolled patients with non-small cell lung cancer with 100% expression of the folate receptor. Patients were randomized to one of three treatment arms: 1) docetaxel (the control arm), 2) docetaxel and vintafolide (combination therapy) or 3) vintafolide monotherapy. The study's primary endpoint is PFS, secondary efficacy endpoints are response rate and overall survival. The study is powered to show a 50% improvement in PFS for vintafolide compared to the control arm. That's a high efficacy bar, difficult to achieve.

Last October, independent data monitors determined that patients treated with vintafolide monotherapy were unlikely to benefit relative to the docetaxel control arm. [Even so, patients were allowed to continue vintafolide monotherapy based on doctor's discretion.] The same monitors recommended the continuation of the combination and docetaxel control arms of the study.

What appears to be "futility" of vintafolide monotherapy in the lung cancer study -- even though that term was not used by independent monitors -- raises significant concerns about the drug's anti-cancer activity and portends equally negative results from the vintafolide-docetaxel combination therapy arm.

I suspect vintafolide is showing poor activity in lung cancer because the vinblastine dose is too low.

1 of 2

Select the service that is right for you!

COMPARE ALL SERVICES
Action Alerts PLUS
Try it NOW

Jim Cramer and Stephanie Link actively manage a real portfolio and reveal their money management tactics while giving advanced notice before every trade.

Product Features:
  • $2.5+ million portfolio
  • Large-cap and dividend focus
  • Intraday trade alerts from Cramer
  • Weekly roundups
TheStreet Quant Ratings
Try it NOW
Only $49.95/yr

Access the tool that DOMINATES the Russell 2000 and the S&P 500.

Product Features:
  • Buy, hold, or sell recommendations for over 4,300 stocks
  • Unlimited research reports on your favorite stocks
  • A custom stock screener
  • Upgrade/downgrade alerts
Stocks Under $10
Try it NOW

David Peltier, uncovers low dollar stocks with extraordinary upside potential that are flying under Wall Street's radar.

Product Features:
  • Model portfolio
  • Stocks trading below $10
  • Intraday trade alerts
  • Weekly roundups
Dividend Stock Advisor
Try it NOW

Jim Cramer's protege, David Peltier, identifies the best of breed dividend stocks that will pay a reliable AND significant income stream.

Product Features:
  • Diversified model portfolio of dividend stocks
  • Alerts when market news affect the portfolio
  • Bi-weekly updates with exact steps to take - BUY, HOLD, SELL
Real Money Pro
Try it NOW

All of Real Money, plus 15 more of Wall Street's sharpest minds delivering actionable trading ideas, a comprehensive look at the market, and fundamental and technical analysis.

Product Features:
  • Real Money + Doug Kass Plus 15 more Wall Street Pros
  • Intraday commentary & news
  • Ultra-actionable trading ideas
Options Profits
Try it NOW

Our options trading pros provide daily market commentary and over 100 monthly option trading ideas and strategies to help you become a well-seasoned trader.

Product Features:
  • 100+ monthly options trading ideas
  • Actionable options commentary & news
  • Real-time trading community
  • Options TV
To begin commenting right away, you can log in below using your Disqus, Facebook, Twitter, OpenID or Yahoo login credentials. Alternatively, you can post a comment as a "guest" just by entering an email address. Your use of the commenting tool is subject to multiple terms of service/use and privacy policies - see here for more details.
Submit an article to us!
DOW 16,979.13 +59.54 0.35%
S&P 500 1,986.51 +4.91 0.25%
NASDAQ 4,526.4820 -1.0320 -0.02%

Brokerage Partners

Rates from Bankrate.com

  • Mortgage
  • Credit Cards
  • Auto

Free Newsletters from TheStreet

My Subscriptions:

After the Bell

Before the Bell

Booyah! Newsletter

Midday Bell

TheStreet Top 10 Stories

Winners & Losers

Register for Newsletters
Top Rated Stocks Top Rated Funds Top Rated ETFs