One of the most important announcements to come from Dendreon’s (DNDN) September 8, 2011, conference call was the fact that the company now is enrolling patients in its FDA Phase 2 trial known as DN24-02: Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma. Its official title is A Randomized, Phase 2, Open-label Study Evaluating DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma. According to information provided by Dendreon on the FDA’s Clinical Trials Web site, subjects will be followed from baseline through the remainder of their lives or until study completion (approximately 5 years). This is the Primary Outcome Measure (no safety issue).
The Phase 1 trial results for DN24-02, also known as Neuvenge, were published in November, 2008. Neuvenge, as is the case with Provenge uses Dendreon’s proprietary antigen delivery cassette technology. It, too, is an investigational active cellular immunotherapy, extending Dendreon’s more than ten years of experience in the development of immunology to other cancers. At the time of the Phase 1 trial, was intended to treat patients with advanced breast, ovarian and colon cancer. However, a re-evaluation of the marketplace suggested that bladder cancer was the preferred target. In the Phase I trials, patients with advanced breast, ovarian and colon cancer underwent three infusions of NEUVENGE over an approximately one month period. (This is the same protocol used today with Provenge.) Patients who achieved a partial response, or had stable disease lasting through Week 48, were eligible for re-treatment with a booster, using the same protocol and dose as the initial treatment.
Even though this was a Phase 1 study, it is both interesting and instructive to review the results. “A total of 37 patients were treated. Results from the integrated analysis showed that treatment with NEUVENGE was generally well tolerated. The majority of side effects were mild, including infusion-related fatigue, fever and chills. The median T cell proliferative stimulation index in response to the immunizing antigen increased from 1.3 at baseline to 19.7 at Week 4 (p=0.0002), 19.4 at Week 8 (p<0.0001) and 20.7 at Week 16 (p=0.02). Immune monitoring performed in three of four patients who underwent repeat treatment suggested an increase in immune response following the booster treatments. Five patients had prolonged disease stabilization ranging from 48 to 94 weeks, without the addition of other cancer therapy other than the continuation of bisphosphonates. In addition, one patient experienced a partial response lasting approximately six months.” To say these results were encouraging is understatement.
Unfortunately, for reasons related to its need to focus on pushing Provenge through the FDA approval cycle, Dendreon was unable to continue with the development of Neuvenge. What funds it had were urgently needed to ensure the successful approval of its new immunotherapy for end stage prostate cancer and the build-out of its three factories. But now, with the launch of Provenge underway, the company has again turned to its second candidate and the initiation of its long-awaited Phase 2 trial.
Why bladder cancer? In 2010, there were an estimated 70,000 cases if bladder cancer diagnosed in the United States. Men, as it turns out, are two to three times more likely to develop the disease than women. Each year, almost 15,000 men and women will succumb to the disease. A portion of patients with urothelial carcinoma overexpress the HER2 protein, which is the target of Neuvenge. For example, J. Buon, in 2009, published a paper in which he studied tumor tissue from 80 patients with primary urothelial carcinoma. Of the 80 patients studied, 41 (51.25%) overexpressed the HER1 protein. The conclusion drawn was that HER2 overexpression represents a prognostic factor for adverse disease outcome.
Bladder cancer usually occurs in people between the ages of 65 and 84, with a median age at death of 78. More than 2% of men and women born today will be diagnosed with bladder cancer during their lifetime. If discovered and treated early, the disease is responsive to treatment and curable. Left undiscovered, and if it metastasizes throughout the body, a metastatic patient has only a 5.4% chance of surviving beyond five years of eventual diagnosis. In addition to the Primary Outcome Measure cited above, this study has the following Secondary Outcome Measures:
- Evaluate disease-free survival following administration of DN24-02 [ Time Frame: Baseline through disease recurrence or study completion (approximately 5 years), whichever occurs first ] [ Designated as safety issue: No ]
- Evaluate the safety of DN24-02 [ Time Frame: Baseline through study completion (approximately 5 years) ] [ Designated as safety issue: Yes ] Safety will be assessed by summarizing adverse events, laboratory evaluations, vital signs, cardiac function, and physical examination findings.
- Evaluate the magnitude of immune response induced by administration of DN24-02 [ Time Frame: Baseline through disease recurrence ] [ Designated as safety issue: No ] Subjects will be evaluated for cellular and humoral immune responses to HER2 following periodic blood draws.
- Evaluate the magnitude of cumulative CD54 upregulation following administration of DN24-02 [ Time Frame: Baseline up to approximately 8 weeks ] [ Designated as safety issue: No ]
The estimated enrollment is 180 patients, with an estimated primary completion Date of June 2016. For eligibility and other criteria, see the FDA Clinical Trial Web site cited above. There are five trial centers in the United States participating in the study (located in Illinois, Indiana, North Carolina, Oregon, and Washington (state).
However you look at it, the initiation of the Neuvenge Phase 2 trial is a very important step forward in expanding Dendreon’s pipeline and in that company’s move to exploit its proprietary antigen delivery cassette technology.
Finally, following what many consider a positive conference call on September 8, 2011, Dendreon's stock is one of the few biotech companies showing "green" on the board today in what only can be called a horrible pre-9/11 market. As we remarked yesterday, the stock is coming off a grossly oversold condition, and the Daily MACD line suggests the Smart Money is moving back into the issue.