It could be third time lucky for Dynavax, with a positive panel vote for its hepatitis B vaccine Heplisav-B pointing to FDA approval on August 10. However, even if the vaccine gets the go-ahead lingering safety worries could hinder uptake, and the company will be on the hook for a large post-market trial.
At least Dynavax, whose stock opened up 84% today, now has the chance to raise money to fund this trial. Whether it is prepared to launch the vaccine itself is another matter – the company’s January restructuring saw it focus on its immuno-oncology projects while looking for a partner for Heplisav-B. Perhaps approval will attract a bigger player but, if not, Dynavax is facing the prospect of going it alone.
Heplisav-B’s second FDA complete response letter in November raised concerns about an imbalance in the number of cardiac events – notably heart attacks – in the HBV-23 study, which compared the product with Glaxosmithkline’s Engerix-B (Snippet roundup: A hit for St. Jude, a knockback for Dynavax and dubious data for Corbus, November 18, 2016). This came after earlier worries over autoimmune adverse events.
In spite of this, on Friday the panel voted 12-1, with three abstentions, that the available data support the safety of the vaccine – with the caveat that Dynavax carries out a post-market study to assess the cardiovascular risk.
The company has proposed a 40,000-patient retrospective observational study to compare the incidence of adverse events, including cardiovascular and immune-mediated events, with Heplisav-B versus other hep B vaccines. Dynavax estimates that enrolment will take five years and results should be available in eight years.
The FDA might want data sooner, or might require a prospectively designed trial – but at least there is now a path forward for Heplisav-B. One advantage it has over existing hep B vaccines is its dosing schedule: it is given twice over one month, while older products are administered three times over six months, meaning some people do not complete the whole course.
But Dynavax already appears to have moved on. In January it slashed its workforce and suspended manufacturing of Heplisav-B in an attempt to reduce its cash burn rate by 40%. At the time the company said it was prioritising its immuno-oncology pipeline, which comprises two toll-like receptor (TLR) 9 agonists, SD-101 and DV281.
The former, which is injected directly into a tumour, is in several phase I/II trials, including Keynote-184 in combination with Merck & Co’s Keytruda in metastatic melanoma. Data from the first 19 patients were reported at last year’s Society for Melanoma Research meeting, and an expansion to include head and neck cancer patients is planned.
Meanwhile DV281, an inhaled project, was due to begin phase I testing in lung cancer in the second quarter, but as yet is not listed on clinicaltrials.gov.
Dynavax is also developing AZD1419, another inhaled TLR9 agonist, in collaboration with Astrazeneca in asthma. The companies believe it could modify the course of disease by “changing the basic immune response to environmental allergens”; while SD-101 and DV281 are designed to elicit an immune response, AZD1419 could help rebalance the activity of T helper 1 and 2 cells, according to Dynavax.
A phase II trial of AZD1419, called Incontro, is currently recruiting.
|Clinical trials of Dynavax assets|
|Trial name||Details||Trial ID||Primary completion|
|Lym-01||Phase I/II trial in combo with radiation in low-grade B-cell lymphoma||NCT02266147||Apr 2018|
|1966-001||Phase I trial in combo with MK-1966 in advanced malignancies||NCT02731742||Dec 2018|
|16703*||Phase II trial in combo with Keytruda + radiation in prostate cancer||NCT03007732||Apr 2019|
|Keynote 184||Phase I/II trial in combo with Keytruda in metastatic melanoma and head & neck squamous cell carcinoma||NCT02521870||Feb 2020|
|LYMNHL0135*||Phase I/II trial in combo with Imbruvica + radiation in low-grade follicular lymphoma||NCT02927964||Nov 2021|
|Incontro||Phase II trial in asthma||NCT02898662||Oct 2018|
|*Investigator-sponsored trial; Source: Company website.|
Heplisav-B might not be the main focus for Dynavax any more, but the unexpected panel nod has given it a boost. If approval follows, along with a partnering deal, the company can put all its resources into the rest of its pipeline.