On May 16th, abstracts were released for many pharmaceutical companies presenting their cancer trial data at ASCO 2012. A highly prestigious and key venue, many biotechs often delay presenting on-going clinical data in favor of presenting at ASCO to introduce or showcase the fruits of their efforts. One huge area of need, due to the severity of its diagnosis and the lack of a successful treatment regimen, glioblastoma (GBM) patients and associated healthcare providers would be disappointed to see that their indication does not even have its own category on the ASCO abstracts listing for 2012. Nonetheless, significant data in the area is being presented at the conference which will likely change the future of its treatment options. Well-known pharmaceuticals and some relative-unknown companies are presenting data that appear to be giving hope to these patients, with Orphan Drug designation being a strong motivator for these companies to pursue this patient set rather than the larger market of breast cancer, colorectal, melanoma, prostate or other more common cancers.
As an apparently under-watched area of need at ASCO 2012, the data will likely speak for itself and may catapult the indication high up the disease watch list as the trial data is recognized and presented by respective pharmaceuticals. Following is a brief summary of the leaders in the field which may represent some of the higher returns for investors as the successes in the indication will likely draw the spotlight for many investors, healthcare providers, stock analysts, and potential suitors. Not all these companies are presenting at ASCO, but comparisons between their released data versus those presented at ASCO can be made. Market capitalization and trial success should be viewed together as possible indicators of potential growth for investors in the coming days to presentations. When viewing the following data, consider the current statistics for newly-diagnosed GBM patients receiving current standard of care of resection, radiotherapy and chemotherapy: The historical mean overall survival (OS) is 14.6 months with a progression free survival (PFS) of 6.9 months. The three year survival is 16% with about 5% survival at 5 years, all indicators of the severity of GBM.
Genentech/Roche (OTCQX:RHHBY) has the most well-known name and drug in the leading GBM therapies. Bevacizumab, marketed as Avastin, has been a huge blockbuster drug for the company. Avastin is a monoclonal antibody that targets and blocks VEGF. Over expressed in cancer cells, VEGF (vascular endothelial growth factor) is a protein that triggers angiogenesis (blood vessel formation). Blocking VEGF has been shown to prevent the growth of these new blood vessels which supply additional blood and nutrients to tumors. Avastin has been approved to treat metastatic colorectal cancer, advanced nonsquamous non-small cell lung cancer, metastatic kidney cancer and recurrent GBM (for adults). Approved for GBM in 2009, the approval was based on two Phase II trials in which tumors shrank in 20 and 26 percent of patients treated, respectively. The effect lasted roughly 4 months before the progression resumed and the treatment surprisingly had little or no effect on survival or symptom improvement. A couple of Phase III trials are underway for GBM; however, no mention of data presentation at ASCO was mentioned in their May 16th press release. Investors and healthcare professionals don't appear to expect an OS or PFS improvement with the Phase III trials, and the company doesn't likely have impressive interim data to tout at ASCO.
ImmunoCellular Therapeutics (IMUC) has been riding on a wave of optimism since its eye-opening Phase I data of ICT-107 for newly-diagnosed GBM impressed investors and the healthcare sector in September of 2011. The trial on the 16-patient set yielded data in which the median OS for the patient set was 38.4 months with a median PFS of 17 months. ImmunoCellular announced approval to begin a Phase II trial in January of this year and hopes its adjuvant vaccine that targets 6 tumor antigens will yield similar results to the Phase I data. An abstract on the ASCO website describes the Phase II trial design and mentions that 120 patients had already been enrolled in the trial which is expected to enroll 200 with at least 102 of those patients being randomized. The company sent out an additional press release on May 31st with an updated 213 patients completing enrollment already! Generally speaking, the speed of enrollment is often an indicator of the marketing potential for a drug, and 213 patients enrolled since January for this trial is impressive. ICT-107 trial inclusion criteria indicate that patients enrolled are HLA-A1 or HLA-A2 positive. Published data indicate this includes over 75% of the human population (depending on ethnicity), a substantial percent of the total GBM patient set.
The company's second abstract at ASCO describes the success of the ongoing data analysis of the original Phase I patient set. As of early February 2012, 6 of the 16 newly-diagnosed GBM patients showed no signs of tumor recurrence (patient set ranging from 44-63 months). This is a 38% survival rate at over 4 years, a substantial improvement over the 10% seen with the standard of care regimen. Medically speaking, any of these patients surviving over 5 years is considered cured. The 16-patient data set is indeed a small sample. However, these results are astounding considering this is a disease in which 95% of patients die within 5 years of receiving the current standard of care. This data set is simply too good to ignore, and any indication whatsoever on comparable interim data for the Phase II trial underway in the future will quickly garner the attention of investors and large pharmaceutical suitors.
Celldex Therapeutics (CLDX) recently made the news not for what it is presenting at ASCO 2012, but rather for the mistake it made in its ASCO submission form in submitting its novel CDX-011 Phase IIb EMERGE trial data for advanced breast cancer. Due to a clerical error, the company will not be posting abstracts on this important trial. However, it will be presenting data on its novel CDX-110 (rindopepimut) plus temozolomide (current standard of care) for GBM. Before delving into the data, the target group of patients must first be examined. CDX-110 targets cells with an expression of the protein EGFRvIII, found in approximately 25-30% of GBM patients which limits the market group somewhat. EGFRvIII is not present in normal tissue, and this should add to the therapy's safety profile as it limits the autoimmune response against normal tissue. Trial data from three different trials were amazingly consistent with OS numbers at 2 years at 50% across the board, an average OS of 24.4 months, and average median PFS of 13.9 months. Celldex initiated a pivotal Phase III trial in December which could mean interim data at ASCO 2014 for 2-year data sets. Although a smaller targeted patient market, lower PFS and lower OS survival per current trial data than ICT-107's Phase I trial, this event could be a huge catalyst for Celldex. However, competing with the Phase III ACT IV data will likely be the 2-year data set for ICT-107's Phase II. With phenomenal Phase I follow up data to accompany it, positive Phase II data would prove the Phase I data set was not a fluke.
Northwest Biotherapeutics (NWBO) is strangely absent from ASCO 2012. Their DCVax immunotherapy drug for NBM has a long but painfully-slow history behind it as the trial switched from a Phase II trial, that initiated in 2006, to a Phase III trial as it is now considered, but with a larger enrollment target of 300 patients. Phase I data was impressive with a median OS survival of 33.8 months, the only data of this group of GBM treatment options that rivals ICT-107's 38.4 month OS. The company has taken steps to speed up enrollment, however the author has concerns about any trial's target patient set and/or efficacy with enrollment at a crawl. Equally concerning is the lack of any enrollment numbers for the last few press releases. Analysts and investors will be watching this biotech carefully in the coming weeks as there should be no legitimate reason an enrollment update can't be provided. As of May, 2011 patient enrollment was at 33, just 11% of its new enrollment goal of 300.
Trial design should always be considered when comparing data against other competing drugs, and it should also be viewed to ascertain its impact on the FDA's final decision for drug approval. The trial's primary endpoint is progression free survival , a variable endpoint due to pseudo-progression. OS is a secondary endpoint, but is complicated by the trial's "crossover policy" which was likely partly implemented to attract additional clinics that may not otherwise be interested in having its patients possibly permanently assigned to the placebo group with very poor prognoses. Ultimately, there may be many questions asked about trial design, true efficacy due to crossover complications, and the primary endpoint. Perhaps outstanding data could erase the doubts, but the current enrollment rate means substantial interim data could be far into the future.
Agenus Inc (AGEN) Prophage Series (HSPPC-96) vaccines contain the heat shock protein, gp96, and associated peptides that are purified from the patient's tumor tissue. This patient-specific approach is being used for both newly-diagnosed and recurrent GBM. Data presented on April 17th at the Plenary Session of AANS was impressive for Prophage Series G-200 on recurrent glioblastoma with 93% of patients still surviving at 26 weeks and a median overall survival of 47.6 weeks. This was a significant improvement over a group not receiving the vaccine with a median OS of 32.8 weeks and a 6-month survival of 68 percent for a (P<0.01) statistically significant correlation. There was a "significant localized tumor-specific CD8+T cell response as well as innate immune responses" indicating a robust response. Not a direct comparison for the newly-diagnosed indication, the data was significant enough to merit a randomized trial for G-200 in combination with bevacizumab (Avastin) for recurrent GBM. Agenus does have a Phase II trial underway for its Prophage G-100 for newly-diagnosed GBM. Enrollment appears to be complete in this 53-patient trial with possible interim data due out in 2013 and a study completion date of 2014 for this trial in which G-100 will be used alongside temozolomide and radiation. Investors can only speculate on G-100, but its G-200 counterpart should be garnering more attention as that trial progresses and could lead analysts to making assumptions about G-100 data which could feasibly be presented at ASCO 2013 and particularly ASCO 2014.
With a smaller targeted market group than many cancers, newly-diagnosed glioblastoma treatment could start showing up on the radar for many investors as therapies begin to improve enough to a point that real hope is offered. ImmunoCellular Therapeutics' ICT-107 appears to be leading the charge in the fight against the dreaded disease. Although presented data is currently all from the Phase I trial, the data is simply too impressive to ignore, with 38% of patients still alive after 4 years with some now over the 5-year benchmark in which they could be considered clinically "cured". Anticipation in the coming months should only build as follow up Phase I data continues and the Phase II appears to rapidly complete enrollment and start marching toward interim data for that trial. Northwest Biotherapeutics' DCVax painfully-slow enrollment rate could now speed up with the recent changes in clinical sites. Investors do need an update on enrollment completion, which is something lacking in recent press releases, including a very recent one on May 17th. With all the success of its Avastin therapy behind and in front of them, Roche's blockbuster drug isn't expected to significantly improve PFS or OS based on earlier trials in which an approval was given not based on those criteria, but rather on tumor response only. Celldex doesn't appear to impress a huge number of investor with its CDX-110 data, although the results are indeed positive. Numbers certainly show improvement, but approval will mean a smaller target set of patients with 25-30% of GBM patients targeted. Celldex's future appears more tied to its CDX-011 metastatic breast cancer drug with impressive data being announced on May 23rd giving the targeted breast cancer patients hope. The race to a GBM cure is progressing at a feverish pace with a very likely winner being assumed at ASCO 2013 and realized at ASCO 2014. Patients, investors, and large pharmaceuticals will be watching this race closely for their varied reasons. Hope could be coming and is likely in the form of at least one of the above-mentioned companies.