The Remarkable Story of the Development of Velcade® and the Model that Explains Its Success
On May 13, 2003, the FDA approved Velcade® (Bortezomib), a proteasome inhibitor (Figure 1), under “Fast-Track” Application for the treatment of multiple myeloma, an incurable cancer of the blood that affects approximately 14,000 patients in the US, annually. The story behind the development of this drug is quite unique and remarkable for many reasons, including:
- The initial fragile funding base of the original company that discovered and developed it (Myogenics/ProScript);
- the risks involved in pursuing a new molecular target (the proteasome) with a new and ill-reputed class of inhibitor (boronates);
- internal struggles and disagreements in the firm between the academic founders and the management regarding the indication for which the drug was to be developed;
- change of the original company’s business model (from cachexia to inflammation to cancer) and subsequent change of the firm’s name—from Myogenics to ProScript; enormously disruptive drop by Hoechst Marion Roussel of proteasome inhibitors for inflammation and cancer and its return of its license rights on the drug to ProScript;
- change in leadership;
- depletion of initial funding and inability to secure further funding for clinical trials;
- the general lack of interest and total disbelief of the biopharmaceutical industry on bortezomib; and
- the resulting merging of ProScript into Cambridge-based LeukoSite and, six months later, purchase of LeukoSite by Millennium Pharmaceuticals.
In spite of all these major obstacles that would have quickly destroyed any company or drug development program, bortezomib managed not only to make it to the market but to do so in record time and at a significantly lower cost than the biopharmaceutical industry’s average.
Why did bortezomib—which was doomed to failure from the beginning—become a success story unlike other countless well-funded examples in the industry? How did it manage to reach the market in record time?
Without knowing and without planning on it, Myogenics/ProScript used an organizational model, which I have called “The Core Model” (Figure 2 and Figure 3; and Animation 1), grounded on the “trade of assets” (exchange of materials, animal models, knowledge, personal connections, etc.) between academia and industry, between the public and private sectors, in a very systematic and effective way. According to this model, the company’s “Core”, formed by the founders, internal people and resources, and the drug “champions”, were very focused on demonstrating the revolutionary therapeutic application of using proteasome inhibitors—and in this specific case, of boronates—based exclusively on the scientific data available and following the biology at every turn. From the beginning the “Core” realized that, given its extremely low economic and technological resources, they needed to acquire more knowledge about the effects of inhibiting the proteasome in vivo, and this could only be accomplished via collaboration and bi-directional interaction with academia and with external, non-competing scientists interested in similar mechanisms or problems. These external collaborators were not only crucial in securing, in many different ways, further knowledge relevant to a better understanding of the biological mechanisms associated to the proteasome and its inhibitors, while providing animal models and validation. They actually allowed the company to save an enormous amount of time, human capital, infrastructure, and money, and—fundamentally—acted as a “Bridge” or “catalyst” between the “Core” and the “Periphery”, that is, all those public resources available in society to sponsor and foster innovation with the objective of creating economic and health care benefits for its members. The “Periphery” includes federally-funded agencies, advocacy groups, philanthropic organizations, consortia, and regulators—all of which contribute with one or more of the following: additional funding for experiments, translational research, and clinical trials; state-of-the art technological platforms; know-how; materials; access to patient populations; drug-development advice; etc., at no cost and without further need of private equity investment or debt, allowing a multitude of “Cores” and “Bridges” to greatly benefit from these readily-available socio-economic resources.
Even though in our day some companies form collaboration in their programs, there is still a great deal of secrecy and misunderstanding of intellectual property (IP), which hinders collaboration—essential for progress in science. In fact, today no company, let alone a biotech startup with limited resources, can do everything on its own. Myogenics/ProScript carried out collaboration with outside groups exceptionally well, as explained by the Core Model, and so particularly benefited from these collaborations at crucial points, both when the company needed scientific knowledge to move forward and when it lacked the necessary economic resources.
The “Core Model”, as epitomized by the success story of bortezomib, emphasizes the potential power of maximizing such collaborative approaches and is useful in providing insights to policy makers, scientists, investors and the public on how the process of drug development can be optimized, which should eventually lead to lower drug discovery and development costs, the creation of better, safer and more effective medicines, and affordable access to the best drugs, including those for neglected and orphan diseases, not only in the developed countries, but also worldwide. Only then will we be able to build a better global system of health care, one which is not only more egalitarian, but also more humane.
Ibis Sánchez-Serrano is moderating the MassBio Forum: Evolution of an Academic Discovery - First Person Account of the Development of Velcade® on Wednesday, July 26.