6.2.15 | Forbes
By Steve Brozak
To read the entire article on Forbes, please click here.
Word of Beau Biden, Jr.’s death stunned the nation. It was a sudden loss, unexpected news that chimed and buzzed over smartphones everywhere and then flashed over television screens across the country. The son of a very public figure, it was very difficult not to feel immediate sympathy for Beau Biden’s father, Vice President Joe Biden. The question remained for many, though, what happened to the 46-year-old son of our Vice President? The answer came a few hours later when the Vice-President announced that his son had lost his battle with brain cancer.
There were passing reports of health issues in the news over the years. In 2010 there were reports that Beau Biden suffered a stroke, but very little focus was given to the illness. A few years later in 2012, Beau Biden appeared on the national stage to nominate his father as candidate for the Vice Presidency – healthy, vibrant and just entering his prime. It was in 2013 when Beau Biden was diagnosed and treated for brain cancer at MD Anderson, a leading cancer center in Texas, where he was cleared of disease. However, some forms of brain cancer are highly recurrent, and it seems as if this may have been the case for the younger Biden who was diagnosed again earlier this spring.
Brain cancer is a disease that comes in many forms, both benign and malignant. Some variants are more easily treated than others and may include hints like sudden loss of vision in one eye or sudden onset of other neurological issues. In some cases a mass can cause a stroke or seizure as it exerts pressure against the brain. In its worst form, the disease is highly recurrent and lethal with few options for practitioners. The standard of care is to resect the main mass if possible, administer a chemotherapy introduced by Merck called Temozolomide, and then deliver radiotherapy to the brain. Temozolomide had peak sales of $423 million in 2012 before Teva and Perrigo partnered to introduce a generic version in 2013. It remains the mainstay of treatment.
In one of life’s frequent twists, I read word of Beau Biden’s death Saturday night as I was analyzing the latest news and data from the American Society of Clinical Oncology’s annual meeting (ASCO), one of the year’s most heralded cancer conferences. Every year companies large and small gather in Chicago to release results from their latest trials. Incidentally, at 9 AM on Sunday was Celldex Therapeutics’ ASCO presentation for a new immunotherapy for brain cancer.
On Sunday morning Celldex issued a press release for its therapy Rintega. Rintega has been tested in multiple clinical trials in Glioblastoma multiforme (GBM), a deadly form of brain cancer. Rintega is a peptide vaccine that blocks the production of a specific protein that promotes tumor growth. Only 30% of GBM patients have this protein present in their tumor, so Rintega would only work in those patients, making it a precision immunotherapy. The results the company shared this weekend in Chicago were around its fourth and final Phase II study. A Phase II study evaluates the effectiveness of a drug and its continued safety profile. Rintega is also in a worldwide Phase III study that is currently ongoing. In this case, the Phase II trial involved 73 patients with GBM in whom the cancer had recurred. The study compared two groups of patients: In the first group Rintega was combined with a blockbuster drug called Avastin owned and manufactured by Roche in 36 patients with GBM, and in the second group Avastin was given alone to 37 patients with GBM which is the current standard of care.
Yet again, the trial demonstrated not only that the drug was safe, but also remarkably effective. Rintega showed significant results across the board in progression free survival, overall survival, and objective response rates. The primary endpoint, which the company met, was progression free survival at six months. In the intent to treat analysis, which is a tougher way to read clinical trial data that includes every patient who participated but did not necessarily complete the trial for various reasons, 28% of patients treated with Rintega survived after six months versus 16% of the group that received just Avastin.
When you take the same data and run an analysis for overall survival (a different measurement using different methods), the results are even more revealing. Excluding those who were unable to complete the trial and conducted a per protocol analysis, 30% of the Rintega patients survived past six months versus 12% of the patients treated with standard of care, Avastin. After 18 months, 30% of the Rintega patients were still alive versus 15% of the Avastin patients according to the intent to treat analysis. In the per protocol analysis, after 18 months 30% of the Rintega patients were still alive versus just 10% of the Avastin patients. What is compelling here is the percentage of patients that are outliving the control group demonstrating that for many patients the survival benefit is clear.
Investors try to read the tea leaves before and after conferences like ASCO, assessing which way a company’s stock will move. A great deal of biotech investing revolves around being able to construct a calendar of potential catalysts based on publicly available information and then investing around those events. Biotech is one of the few areas of investing where there is an abundance of binary events outside of earnings seasons. It also comes with an abundance of data that must be expertly parsed. Comparing the intent to treat versus per protocol data is just one set of analysis and comparisons that can be run among thousands of others. In this instance for Celldex, the FDA set the bar for the trial at progression free survival at six months with a number of secondary endpoints. After reviewing all of the information made public by the company this weekend, a few things can be surmised:
• Rintega combined with Avastin prolonged life in patients with GBM significantly over patients who were just given Avastin
• Celldex achieved its primary and secondary endpoints remarkably
• Rintega elicited a strong immune response, meaning that it behaved in the patients’ bodies as expected
• Rintega was combined with Avastin and demonstrated less toxicity and fewer side effects as compared to the group that was just given Avastin. This means that Rintega drastically reduced the side effects of the disease and Avastin while also improving outcome. Steroids were used heavily to lessen side effects in the group of patients who only received Avastin. Use of steroids in patients can be a dreadful experience.
The primary data for Rintega now must hold up in its Phase III trial that is focused on newly diagnosed patients with GBM. Initial data is expected from that trial later this summer. With all of the current data, there is no telling what the FDA will do, but with a dearth of treatment options it may very well come time for the FDA to consider an accelerated approval for Celldex’s drug. As a comparator, Avastin was approved to be used in GBM on the basis of a relatively small Phase II and received accelerated approval in 2009. The primary end point for that study was objective response, or the amount a tumor mass responds to a drug therapy. Objective response was a secondary endpoint in the Rintega Phase II trial.
Celldex’s announcement at this year’s ASCO was made more poignant with news of Beau Biden’s death on the eve of the company’s release. While we have all experienced disease, rarely do we have an opportunity to put a public face to a cause so strikingly as occurred this weekend. We will never know whether or not Celldex’s drug would have made a difference for Beau Biden, but we do know that his life did make a difference for all of us.