DCVax-L in the Treatment of Glioblastoma: Phase 3 Passed and prospects as a new Standard of Care
In this article, I try to answer, as precisely and completely as possible, the questions that I received through the comments on the articles on research news.
DCVax-L, an innovative personalized vaccine for the treatment of glioblastoma multiforme (GBM), has shown significant results in phase 3 clinical trials, with substantial improvements in median survival in both newly diagnosed and relapsed glioblastoma patients. Northwest Biotherapeutics has already submitted a marketing authorization application in the United Kingdom, where approval appears imminent, while approval in the United States is expected to follow. Despite promising clinical results, adoption as a standard of care will depend on several factors, including effective regulatory approval, widespread availability, and affordability, considering that current costs could be in the range of $200-300,000 per treatment cycle.
The Phase 3 clinical trial (NCT00045968) of DCVax-L demonstrated significant results that were published in the prestigious journal JAMA Oncology. This study represented an important step forward in the search for effective treatments for glioblastoma multiforme.
Clinical data reveal statistically significant improvements in patient survival. In patients with newly diagnosed glioblastoma treated with DCVax-L in addition to standard therapy, the median survival was 19.3 months compared to 16.5 months in the control group that received standard therapy alone (p = 0.002). This represents a gain of almost 3 months in median survival, a clinically relevant result for a disease characterized by a poor prognosis.
Even more impressive were the results in patients with recurrent glioblastoma, where treatment with DCVax-L led to a median survival of 13.2 months versus 7.8 months in the control group (p < 0.001), almost doubling the survival time. This is particularly significant considering that survival in recurrent GBM has not improved in the last 30 years.
A particularly promising aspect of the DCVax-L studies concerns long-term survival. The data show that survival at 48 months (4 years) was 15.7% in the experimental group versus 9.9% in the control group. Even more impressively, 60-month (5-year) survival was 13% in patients treated with DCVax-L compared to 5.7% in the control group, with the longest-living patient still alive 8 years after randomization.
These results are consistent with previous data from Phase I/II, where 33% of patients reached or exceeded a median survival of 4 years and 27% reached or exceeded a median survival of 6 years. Importantly, two patients in the Phase I/II studies even exceeded 10 years of survival, a remarkable result considering that with the current standard treatment, the median survival is only 14.6 months.
DCVax-L is a personalized therapeutic vaccine that uses a patient’s own immune system to fight cancer cells. The manufacturing and delivery process is complex and highly personalized for each patient.
The treatment begins with a process called leukapheresis, a 2-3 hour procedure during which dendritic cells, key components of the immune system responsible for presenting antigens, are extracted from the patient’s blood. At the same time, 2-3 grams of the patient’s most recent tumor sample is needed, stored at -57°C.
The tumor tissue is then broken down using specific enzymes, creating an “autologous tumor lysate” that is exposed to the extracted dendritic cells. This process allows the dendritic cells to develop antibodies specific to the patient’s tumor and learn to recognize it. The “educated” dendritic cells are concentrated and stored in vials in liquid nitrogen. This process is where all the difference lies in terms of the effectiveness of personalized vaccines with dendritic cells, which obviously are not all the same and are not all equally effective.
The vaccine is then administered to the patient via an intradermal injection in the arm, similar to a flu vaccine. Once injected, the dendritic cells move towards the lymphatic system where they interact with T lymphocytes, activating them against the tumor and stimulating the entire immune system to recognize and attack the cells.
tumors.
Northwest Biotherapeutics has submitted a Marketing Authorization Application (MAA) to the UK Medicines and Healthcare products Regulatory Agency (MHRA) for DCVax-L to treat glioblastoma. The application seeks approval for the vaccine to be used in both newly diagnosed and recurrent cases of glioblastoma.
The company has also requested that the application be considered under the 150-day fast-track review pathway, a special program the MHRA has established for new medicines to address serious unmet medical need. This could significantly speed up the approval process in the UK.
According to available information, UK approval appears imminent, and is expected to follow in the US. In February 2022, Northwest Biotherapeutics announced that it is able to manufacture the vaccine in the UK for people who wish to access it privately, albeit at a very high cost.
The question of whether DCVax-L will become the new standard of care for glioblastoma depends on several factors. The clinical results are certainly promising, but the path to adoption as a standard treatment requires additional steps.
First, formal approval from regulatory authorities is needed. While approval in the UK seems likely in the short term, global adoption will require approval from other regulatory agencies, such as the FDA in the US and the EMA in Europe.
Second, affordability will be a determining factor. Currently, costs are in the range of $200,000-$300,000 for a course of treatment, a price that could significantly limit access to the treatment. Whether national health systems or private insurance will cover the treatment will be crucial in determining its uptake.
Finally, there are logistical considerations related to the personalized nature of the treatment. Manufacturing DCVax-L requires specialized facilities, access to fresh tumor samples, and complex manufacturing and storage protocols. The scalability of this process will be critical to its widespread adoption.
Given the current state of the application process and typical regulatory timeframes, it is reasonable to expect that DCVax-L could receive approval in the UK by late 2025 or early 2026, especially if expedited review is granted.
Approval in the US and other countries could follow in the next 12 to 24 months, depending on the speed with which Northwest Biotherapeutics submits applications to their regulatory agencies and the complexity of the review process.
However, even after approval, it will likely be several years before DCVax-L can be considered a universally accepted standard of care. This will depend on factors such as:
- Inclusion in national and international clinical guidelines
- Implementation of large-scale manufacturing and distribution infrastructure
- Price negotiation with national health systems
- Education of healthcare professionals on the appropriate use of the therapy
- Accumulation of real-world efficacy and safety data outside of clinical trials
DCVax-L represents a promising innovation in the treatment of glioblastoma multiforme. Results from phase 3 clinical trials show significant improvements in survival, both in patients with newly diagnosed and relapsed disease.
The submission of the application to the UK MHRA marks an important step towards the clinical availability of this treatment. If approved, DCVax-L could become an important new treatment option for patients with glioblastoma, potentially changing the current treatment paradigm.
However, the transition to standard of care status will take time and will depend on factors such as regulatory approval in multiple countries, affordability and scalability of manufacturing. It is reasonable to expect that this process will take several years, with a possible phased adoption starting in 2026-2027 in regions where the treatment is approved first.
In the meantime, patients and physicians should stay informed about developments related to DCVax-L and consider accessing the treatment through private channels where available, or through any early access programs that may be implemented while waiting for official approvals.
