CureVac gets first mRNA vaccine data in humans; waits for next step
This article was originally published in Scrip
CureVac, a small mRNA vaccine company in Tuebingen, Germany has shown that its CV9301 product for hormone-refractory prostate cancer is safe, well-tolerated and can elicit both a cellular and humoral immune response in a a high percentage of trial subjects. The data, from an open lable Phase I/IIa trial, announced on 4 October, are the company's first clinical results but the company now plans to wait for further results from an ongoing Phase I trial of a second product, CV9201 in non-small cell lung cancer before finalising its development strategy. "What is clear is that we don't stop here," said CEO Mr Ingmar Hoerr. "But how the product goes forward is unclear." The company will follow the prostate cancer patient outcomes for a year and then decide on its strategy. He explained that CureVac saw the results on CV9103 as the proof of concept that mRNA-based vaccines can stimulate a human immune response against a range of antigens.
The 9301 prostate cancer vaccine is, in effect, a single strand of modified mRNA that encodes four prostate cancer associated antigens: prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), prostate stem cell antigen), and STEAP (Six Transmembrane Epithelial Antigen of the Prostate). They are produced from a single stretch of pseudo-mRNA, CureVac's RNActive® technology, which is injected intradermally. Apart from PSA which is a soluble antigen, the other three elements of CV9103 are membrane-crossing proteins which – the company argues - might be difficult to express in protein-based systems.
According to the company's CSO, Dr Kajo Kallen, the trial data show that each of the antigens expressed from its mRNA product can activate both T-helper and T-cytotoxic responses, at least in some subjects. Over 70% of the 32 study patients in the phase IIa part of the trial responded to at least one antigen out of the four antigens in CV9103 and 50% responded to at least two of them. "We feel that we are now stepping on pretty safe ground," Dr Kallen added, "and we are confident in exploring the data with potential partners."
Dr Kallen said it was too early to make any judgement about the clinical benefit of the vaccine. "We will follow the patients for a year and collect survival data," he said. "We have seen a good immune response, and we know from other [product's] studies that T cell responses are important for controlling the tumour. We want to be able to increase the spectrum of the response," he explained.
The follow-up from previous early trials of prostate cancer vaccines have show a good correlation between immune responses and clinical improvement. For Bavarian Nordic's ProstVac which is a poxvirus-carrying-PSA product, immune responses appeared to correlate with clinical activity (May 20, 2009 J Clin Oncol 27:15s, 2009 suppl; abstr 5144). However, the immune responses studied have been largely restricted to those against PSA: the relevance of responses to the other antigens in the CureVac product is unknown
Compared with the Bavarian Nordic product and with Dendreon's Provenge, CureVac believes that its approach has the advantage of simplicity of composition and of administration. ProstVac requires separate initial innocation and booster products, while Provenge is an autologous cell product.
The business development on CV9201 begins now, according to CEO Ingmar Hoerr. "This is the proof of concept and we are having conversations with pharma companies now," he said. However, the business direction for the company is unclear. "We might enter a funded collaboration," says Mr Hoerr, "or run the project in house, or with a risk-sharing element, or do something completely different. We are completely agnostic as to which way would go."