Dynavax Sinks 32% As FDA Cancels Its AdComm Meeting
On Friday, shares of Dynavax Technologies (DVAX) tumbled by 32% after the FDA announced that it had cancelled the advisory committee meeting scheduled for November. The ad comm was supposed to review Dynavax's drug for Hepatitis B, known as Hepislav, in November for the FDA. The decision on whether or not to approve the drug would have come one month later in December.
What really feels odd is that neither the company nor the FDA gave an adequate reason to why the ad comm meeting was cancelled. The only thing that the FDA has cited is that it needs more time to "review and resolve several outstanding issues." But unfortunately no indication is given of what issues need to be fixed.
DVAX's Hepatitis-B drug has already had a rough path with the FDA. Back in February of 2013 the FDA gave the drug a Complete Response Letter -- CRL -- citing that there were several safety issues associated with the older age population. More specifically, there were a lot of autoimmune events in patients that were given the drug.
With the prior CRL, and now this cancelled ad comm meeting, it doesn't bode well for the future of Dynavax. As much as I would like to recommend the stock to investors, I would say it would be wise to steer clear of this one. Hepislav-B had safety issues in the past, and now this cancelled ad comm meeting doesn't bode well either. Plus the FDA's response is too vague.
All the FDA said is that it will continue to evaluate the drug, and issue a meeting if necessary. That doesn't sound like the FDA is confident to approve the drug in its current form. Having said that, the stock should continue to fall until there is more clarity from the FDA. The speed at which the FDA works is not quick, therefore a lot of investors will be left hanging for months without knowing the real reason the meeting was cancelled. It is best to stay away from buying shares in Dynavax for the time being.
Disclosure: None
Terry, I think you could have spent a little more time with the literature and dug up more material to help your readers understand better what might be going on in the FDA's mind.
Here's what the FDA had concluded in their briefing materials prior to the last (actually, the first) AdCom:
"Immunogenicity data supporting lot consistency was shown, and HEPLISAV was non-inferior to Engerix B with respect to seroprotection rates in this second pivotal study. The overall rates of solicited and unsolicited AEs, SAEs and AESIs were similar among the consistency lots, the older manufacturing lot TDG006, and Engerix-B. No significant differences in [anti-nuclear antibody] ANA titers or [Anti-Double Stranded DNA] anti-dsDNA levels were seen among the different treatment arms. While the incidence of autoimmune events was low, all autoimmune AEs occurred in HEPLISAV recipients. Given the randomization ratio employed in this study and the low background incidence of many autoimmune diseases, the clinical significance of the 0.5% difference in the incidence of potential autoimmune disease between groups is unclear. Due to the reports of thyroid disorders, an independent CBER analysis revealed that thyroid related AEs were reported by HEPLISAV recipients with a frequency similar to that of Engerix-B recipients and the background incidence rate across all studies. As the numerical differences in the incidence of these AIAEs in this study did not persist upon integrated analysis of all studies, CBER determined that study DV2-HBV-16 did not reveal clinically significant safety concerns. However, it is acknowledged that the ability to reliably evaluate uncommon specific autoimmune events is limited due to the size of the study."
That said, you are correct in that the CRL was issued because the agency felt there were insufficient data in some areas (e.g., minorities, certain age groups) that prevented assessments of safety-related issues. For this reason, a third Phase 3 study was conducted. An overview of the results for this study can be found here:
investors.dynavax.com/releasedetail.cfm
From this URL, importantly:
HBV-23 was a randomized, observer-blinded, active-controlled, multi-center study. Participants were randomized to HEPLISAV-B or Engerix-B in a two to one ratio. They were stratified into two age groups, 18 to 39 years and 40 to 70 years. Two doses of HEPLISAV-B were given one month apart compared to the conventional Engerix-B regimen of three doses given over six months. HEPLISAV-B participants were followed for 52 weeks after the last dose, and Engerix-B participants were followed for 28 weeks after the last dose.
HEPLISAV-B demonstrated statistically significant higher protection rates than Engerix-B in both age groups. The seroprotection rate in all participants who received HEPLISAV-B was 95 percent compared to 81 percent for Engerix-B. Of participants 18 to 39 years of age, 99 percent who received HEPLISAV-B and 93 percent who received Engerix-B were seroprotected. In participants 40 to 70 years of age, a larger difference in seroprotection rates was seen with the HEPLISAV-B rate of 95 percent compared to 79 percent for Engerix-B.
The rates of local and systemic reactions, adverse events, serious adverse events, and deaths were similar between the HEPLISAV-B and Engerix-B groups. All adverse events considered to represent potential immune-mediated disorders were reviewed by an independent, blinded Safety Evaluation and Adjudication Committee and classified as not related to vaccination. Of the new onset immune-mediated adverse events, Bell's palsy occurred in 0.09% of HEPLISAV-B and 0.04% of Engerix-B participants. Additionally, in the HEPLISAV-B group, there was a single case each of alopecia areata, polymyalgia rheumatica, and ulcerative colitis. With the HBV-23 trial, the total safety database now comprises 14,238 participants: 10,038 of whom received HEPLISAV-B and 4200 of whom received Engerix-B.
So, the bottom line is this: the combined, three-trial database now comprises over 14,000 patients, more than sufficient (I believe) for the agency's purposes. There is no question that HEPLISAV is superior to the GSK product. On safety, it appears the two products have similar profiles.
So, what's going on? I think that because DVAX's product uses an adjuvant, the FDA is being extra careful with its review and taking whatever time it wants and needs to ensure that the data are scrubbed to a fare thee well before the next AdCom is held.
Thanks for taking the time to share all this info.