GSK's thirst for adjuvants grows
to supply it with more of its QS-21 adjuvant as its vaccines
progress in the pipeline, while at the same the British drug giant
is pushing ahead with its own adjuvant, MPL, seeking not just
clinical but also manufacturing benefits.
With the global vaccine market booming, GSK is currently engaged in an arms race with other big vaccine manufacturers such as Chiron and sanofi pasteur to develop new vaccine formulations that do not use aluminum salt (alum), the conventional widely used adjuvant designed to enhance the body's immune response to the antigen contained within the treatment.
Although alum is regarded as generally safe, cheap and has been used since the 1940s, it only prevents degradation or discharge of the antigen and does not have any immunostimulatory properties in its own right, something expected from a modern adjuvant today.
In its quest for a new generation adjuvant, GSK currently has vaccines with twelve indications in clinical trials and another eight in preclinical development, all using QS-21, a purified immunological adjuvant derived from the bark of the tree Quillaja saponaria and developed by Antigenics.
QS-21 is a water soluble triterpene glycoside with amphiphilic character that can be mixed with a soluble antigen in a fully soluble vaccine formulation or combined with emulsion or mineral salt adjuvants.
Because of the ability of QS-21 to improve the body's immune response to very low doses of antigen, vaccine antigen may be "spared," which could significantly decrease the amount of antigen required for a given dose and make vaccine production more economical.
As more of GSK's vaccine candidates reach Phase III stage and require more clinical-grade material, the second largest drugmaker in the world has now decided to expand its licence and supply agreement with Antigenics for QS-21 until 2014 but also obtain the manufacturing technologies for the adjuvant.
In-PharmaTechnologist.com has learned that the vaccine candidate furthest ahead in GSK's pipeline formulated with QS-21 is a malaria vaccine expected to be in the market by 2010.
P. falciparum, the bacterium which causes more than 2m malaria deaths annually, has frustrated the efforts of many researchers who have been working for years to develop a vaccine against it.
However, GSK has had success in the malaria vaccine using QS-21 in combination with two other adjuvants, one of which is MPL, a derivative of the lipid A molecule found in Gram-negative bacteria.
MPL was developed by US firm Corixa which GSK acquired last year for €233m, relieving itself from the burden of royalties.
Fendrix, a Hepatitis B vaccine by GSK, has already been approved in Europe using MPL as an adjuvant, with several more vaccines that use this adjuvant in their formulation moving forward in GSK's pipeline, including those for tuberculosis and genital herpes.
Last week GSK said data published in Vaccine shows that its cervical cancer vaccine candidate formulated with its proprietary MPL-based AS04 adjuvant system induced not only higher and more sustained antibody levels against the Human Papilloma Virus (HPV), but also a more robust immune memory response compared to alum.
GSK is of course working with several investigative adjuvants made by other companies, such as VaxImmune developed by Coley Pharmaceutical Group, but the fact that clinical trial results with QS-21 have also been positive so far has stirred speculation about whether Antigenics can share Corixa's destiny and eventually be acquired by GSK.
"QS-21 is quickly becoming the gold standard in vaccine manufacturing with the adjuvant being evaluated in more than 50 different indications," Antigenics spokesman Sunny Uberoi told In-PharmaTechnologist.com.
"Apart from GSK, sanofi pasteur, Progenics, Wyeth and Elan have licenced our adjuvant and use it in their vaccine development."
Upon successful commercialisation, products from these partners would collectively represent up to $25bn (€20bn) to $30bn in annual revenue potential for Antigenics' licencees and collaborators, which in turn would mean potential annual royalties for Antigenics in the hundreds of millions dollars, the company said.
GSK will make payments contingent upon successful milestone achievements and will pay royalties to Antigenics on net sales for a period of at least ten years after first commercial sale under the supply agreement.
QS-21 is manufactured at Antigenic's Lexington facility in Massachusetts which can produce 200,000 doses per batch, while key elements of the production process have been scaled to 2m doses per batch in anticipation of commercial-scale implementation.
Since the global vaccine market is expected to quadruple in size by 2015 to £17-£24 bn from its current level of around £5 billion (€7.4bn), specialised firms like Antigenics are likely to continue to benefit from the search of vaccine manufacturers for improved adjuvants.
