Heights And Plights Of Vaccine Development: Tales From The Frontline

Gary Dubin, senior vice president and global medical officer in Takeda Pharmaceutical Co.’s Vaccine Business Unit, talks about the trials and tribulations of vaccine R&D and how it felt to get one of the world's first human papillomavirus injections to market.

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Takeda's Gary Dubin talks about the risks and rewards of vaccine development

Dubin joined Takeda Pharmaceutical Co. Ltd. in 2015 following a long tenure at GlaxoSmithKline PLC, where he was responsible for the clinical development of the UK big pharma's Cervarix vaccine – one of the first human papillomavirus (HPV) vaccines, which is now used worldwide to protect women against cervical cancers. Now, Dubin oversees medical affairs and safety activities within Takeda's vaccine business unit and acts as the program lead for the company's Zika virus vaccine candidate. He talks to Scrip about life in vaccine development.

Scrip: What was your first pharma job?

By background I'm an internist and infectious disease physician; I was in academic medicine before joining industry. I'm also a molecular virologist and have always been passionate about vaccines. When I was working in academia my research focused on trying to develop candidate vaccines against herpes simplex virus (HSV) and my first job in the industry, at GlaxoSmithKline, came directly out of that experience. In 1995, when I joined GSK, I worked on the development of an HSV vaccine and had been working in the lab for many years on this virus. It was really exciting to lead a vaccine development program in an area that I was very familiar with. My laboratory research was very interesting and it was progressing nicely but I wanted to be in a role that had more direct impact on public health.

Gary Dubin, senior VP & global medical officer in Takeda's vaccines Unit

Two years after I joined GSK to work on the HSV vaccine, I was given a unique opportunity. I was asked to take on a “small” side program for a vaccine that had just been newly licensed by GSK. That program was to develop a human papillomavirus vaccine. I spent the next 10 years of my career leading the GSK HPV clinical development program from initial discovery work to licensure in 120 countries and it is really one of the highlights of my professional career. When I began my work on HPV, I could not imagine anything more important than trying to develop the world’s first cancer vaccine. HPV vaccines, of which there are now several, are hugely important and are having a major impact on cervical cancer, the second leading cancer in women worldwide.

What piqued your interest in vaccines early on?

Vaccines are amazing public health tools. When I went into medicine I did not necessarily expect to be doing what I'm doing today but I'm really driven by my passion to contribute to public health. I've had enormous opportunities to aid in the development of many important vaccines. I feel very lucky to have been able to work in vaccine development, and to now continue my work on vaccines at Takeda.

You talked about the success of GSK's HPV vaccine as being a highlight of your career: is there one moment of that R&D journey that you would spotlight?

The development of an HPV vaccine required a long and complex program but an event that stands out for me is the presentation of our development program to the FDA Vaccine and Related Biological Products Advisory Committee in 2009. Up to this point, the GSK HPV vaccine had been licensed in many countries around the world but we were not yet licensed in the US. The FDA was quite nervous about licensing a vaccine that had a novel adjuvant, as there had not been a vaccine licensed with a novel adjuvant for 30 to 40 years. The FDA had set the bar very high.

At the brink of licensure, our vaccine program was presented to the FDA Advisory Committee and I had to present most of the data. At the end of the meeting the Advisory Committee gave a favorable recommendation. This was hugely important for the company and it was also hugely important in terms of making an important vaccine available to women in the US. In front of the committee, I had to address all their questions, which were many. We brought lots of data to the table and ultimately within two or three months, the vaccine was licensed. This became a major milestone, not only for GSK but for the vaccine industry, because suddenly it opened the door for the introduction of other vaccines that were being developed with novel adjuvants. Since then there have been many vaccines that have been licensed in the US with novel adjuvants, but GSK's HPV product was the first.

On the flip side, what has been the most difficult moment in your career?

That's easy, surprisingly. I mentioned that I joined industry at GSK to lead a development program for a herpes simplex virus vaccine – and we actually started HPV vaccine development activities several years after the HSV development program was initiated. Within 10 years of starting development, the HPV vaccine was broadly licensed, but to date there are no HSV vaccines that have been successfully developed; we spent 20 years trying to develop that vaccine and ultimately failed. That was the most difficult moment for me, to fail in the development of a herpes vaccine.

However, I learned that some development programs are more straightforward than others. HPV is the prototype of a development program that just went well; in the first efficacy results produced, we saw essentially 100% protection. You don’t see that very often. At the other end of the spectrum some vaccine development programs are difficult, because the targets are difficult. I think HIV (human immunodeficiency virus) falls into this category, along with HSV and RSV (respiratory syncytial virus). It doesn’t mean that you shouldn’t choose challenging targets, but to succeed in some of these challenging programs we are going to need more innovative technologies.

Who do you admire in the industry and why?

I really admire what Bill and Melinda Gates have done to support the vaccine industry. The work of the Bill and Melinda Gates Foundation has been transformational; there are many vaccine programs that would not have progressed if the Foundation hadn't created a successful model for public-private partnership. At Takeda, we’re excited to partner with the Gates Foundation on the development of our polio vaccine, which will enable us to manufacture and provide access to a Sabin inactivated polio vaccine for developing countries. This will be an important component in the polio eradication endgame.

One of the vaccines that my team at GSK developed was the RTS,S malaria vaccine. This vaccine would likely not have been developed were it not for the support of the Gates Foundation and other groups that were willing to collaborate and help fund the development program. This vaccine is not very attractive commercially but is important from a public health perspective, and because of public/private partnerships it's been successfully developed and licensed, and will soon be implemented in malaria-endemic countries in Africa. This is a shining example of how the Gates Foundation has transformed the industry.

What changes have you effected since joining Takeda?

With the recent growth in headcount and the number of portfolio programs in Takeda's Vaccine Business Unit, the company needed to better structure its activities. I and many others like me who have come to Takeda from mature vaccine organizations and who have experience in the development and commercialization of vaccines have been able to put in place structures and processes that will ultimately help ensure that Takeda can achieve its ambitions. Our ambition is not only to develop but to appropriately launch and commercialize vaccines that target important infectious diseases with global impact.

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What I've learned is you can't just take the kinds of things that might work in a large company like GSK and apply them to Takeda's smaller vaccine unit: that doesn’t work because we're very different. To date, I believe we have been able to find a very good balance and bring the right level of structure while not imposing obstacles to innovation and agility.

Almost every day I find myself thinking, ‘Okay, who else do I need to get this decision approved?’ because in a large organization there are many levels of hierarchy. But in Takeda we do not have many hierarchical levels and the decision-making process tends to be agile and streamlined. It's very different from what I was used to. We're still developing as a unit but are clearly moving in the right direction. I've been very happy since I joined Takeda.

What is your long-term vision for Takeda’s vaccine business?

Our midterm vision is to develop the four vaccines currently in our pipeline and see them appropriately commercialized. The pipeline includes candidate vaccines against dengue fever, Zika virus, polio and norovirus. Longer term, I believe that Takeda has the potential to continue to develop as a vaccine organization that will be able to successfully address other infectious disease threats.

For example: our Zika program will help prepare us for, and potentially help position us as a company that can rapidly address emerging infectious diseases. This is an important area because the environment we live in seems to be producing more and more emerging infectious diseases, especially as populations expand geographically into areas that result in more contact between humans and animal virus reservoirs. These are diseases that have been quietly circulating in animals for many years which are now jumping species. That’s essentially what we've seen with Zika. I believe we are going to continue to see urbanization result in new emergent infectious disease threats. This is an important and exciting area where Takeda can contribute.

Since joining Takeda, it’s been exciting to work creatively and collaboratively in the fight against global infectious diseases. We’re keenly focused on forging partnerships with leading institutions and collaborating across our functional areas to identify innovative vaccine development platforms. It’s my hope that our culture of collaboration and partnership will continue to expedite the development of potentially life-saving vaccine candidates, as well as their distribution to the populations who need them most.