How Medicine Can Highlight the Markers of

a Civilization
Our priorities paint a picture of who we are, and that’s as true in RNAi medicine development as
it is elsewhere in life

Angus Stewart | 01/31/2023 | 8 min read | Interview

Kasha Witkos is the head of Alnylam’s international division, which puts her in charge of
operations across Canada, Europe, Japan, Australia, and New Zealand. Her company’s mission is
to develop RNA interference (RNAi) medicines for diseases that have limited and inadequate
treatments. We spoke to her about this work, her own career, and how each has intersected with
questions around rural poverty, prison healthcare, island populations, visions for the future, and
the values that constitute a civilization. Sound a little grandiose? Read on to find out how all
these lessons link up.

Did you always want a career in pharma?

At first, absolutely not! When I began planning my future, I was barely aware of the
pharmaceutical industry. Instead, I was on the path to my (then) dream – becoming a physician.
This led me to move from Europe to North America and, in the US, I ended up switching to
genetics. I trained as a scientist and did my first work at the University of Colorado and at
Northwestern University Medical School in Chicago. During those years, I realized that 24/7
research was not for me. I wanted to serve patients and make more of a difference than is
possible from a lab. When you’re a researcher, you often don’t see the fruits of your labor. So I
began searching for pharma jobs and eventually moved into the industry.
What did your early pharma jobs teach you?

I started out in roles that probably no longer exist today. My very first job was a field-based role,
working directly with physicians, nurses, and hospital administrators. It was partly scientific,
partly medical, and partly commercial. It helped me understand the full gamut of the various
roles people play across all of medicine, how the ecosystem works around the patient, and how
important it is to connect the different parts of that ecosystem.

My early work in the US had its own multidisciplinary dimension, too. I’ve worked across
specialties and setups – from very small clinics in rural California to university centers in San
Francisco to supporting physicians inside correctional facilities. I’ve seen extremely organized
healthcare systems in huge university hospitals kitted out with all the very best equipment and
manned by the very best professionals and I’ve seen tiny medical centers in the nation’s
impoverished backwaters.

This taught me not only about the complexities of healthcare systems, but also about how the
complexities of society affect those systems. I learned that, to treat patients, you need to place a
serious focus on external networking and collaboration.

What was it like working in correctional facilities?

To enter, I first had to secure a number of approvals. It was horrendous. Some of the facilities I
covered were very strict; these were for lifelong prisoners. However, I was glad to see that even
these prisoners have access to modern, innovative treatment options. I appreciate being given the
opportunity to enter that place and support that access. I would say that the way we handle our
obligations to such populations, despite their crimes, is one of the markers of civilization.

Across your career, what emerging innovations have caught your eye?

I’m a geneticist by training so, for me, the field of gene silencing and RNA interference is
absolutely fascinating. It is amazing how we can harness a natural biologic process called RNA
interference – that regulates gene expression by “interfering” with messenger RNA – to “silence”
or turn off the production of specific genes that cause disease or that contribute to disease. The
delivery methods have proven challenging but, in our lifetimes, we are seeing the dream become
a reality. For example, bringing short interfering RNA into liver cells was very difficult, but
researchers across the world overcame the challenges. I studied and worked on the process for
years as a geneticist – and now I can see it applied in the clinic and meet real human beings who
have benefited from these therapies.

We may all be too old to see a wave of cures arrive in our lifetimes, but we’re willing to work to benefit
the people who will come after us.
Which unmet need do you think about the most?

I connect most with rare diseases. Scientists have estimated that there are around 7,000 rare
diseases, some of which we class as “ultra-rare.” Of these, I think 95 percent have no treatment
or no foreseen treatment. Many patients with these conditions have unmet needs and many of
these conditions – especially the ultra-rare ones – are genetic in nature, which means they often
impact the patient from the earliest days of their lives. I think we could massively improve a
great number of lives by cracking the code.

For families who have a child with a rare disease, there is often not only no cure, but no
treatment – only palliative and supportive care. We call these diseases “rare,” but when one is
harming your family, it doesn’t feel rare at all; it’s right in front of you. Worse yet, these
conditions can often be passed down from one generation to the next.

As medicine makers, we can find some hope in the fact that, in the world of rare diseases, you
can apply learnings from one disease to a broader range of conditions. We can also be glad that
the relevant patients are highly engaged with clinical trials; in my own work, I can say that we’ve
never had problems with trial recruitment. Across patients and researchers, there is a serious
commitment to the next generation. We may all be too old to see a wave of cures arrive in our
lifetimes, but we’re willing to work to benefit the people who will come after us. This
willingness is another one of the markers of civilization. These are the kinds of endeavors to
which we should be committing our resources.

Alnylam has a diverse leadership team. Does that influence its approach to drug development?

Every angle of diversity is important, and diverse identities within a company’s leadership can
help reinforce diversity of thoughts, views, and experiences. It’s key, too, that our organization’s
workforce reflects the diversity of the patients we serve. This internal diversity influences how
we conduct everything from research and clinical trials through to access.

We try to be proactive in ensuring that our clinical trials include the endemic populations we
serve in each disease area. Most ultra-rare diseases are genetic, which means they can become
widespread in “founder” populations in which a small number of “forefathers” give rise to an
isolated population with a very limited gene pool. Among such populations, there is a strong
chance for an increased number of individuals to be born with rare diseases. For example,
hereditary transthyretin amyloidosis (hATTR) appears in large endemic regions of northern
Portugal, northern Sweden, and northwest Ireland. Islands are also common sites for endemic
rare diseases – for example, Majorca, Sicily, Japan, and the Caribbean.

Across the next decade, I hope to see innovation everywhere.

All of this means that, when we run our clinical trials, we need to ensure that these populations
are properly considered and represented. One way we achieve this is through collaborations with
specific institutions that can help us augment our samples. We also make sure that we begin
speaking to the relevant patients early on in a manner that is fully compliant, but also meaningful
for them. We want to find out what matters to patients in each specific disease area.

2023 is here – but how would you like pharma to look when 2033 arrives?

For me, it has to be about service and partnership. We need to work as partners with the various
stakeholders in each of the countries where we operate – and this means forming partnerships
with regulators, payers, and the medical community. Along those lines, I also believe that
public–private partnership is one possible future for pharma. We have some great examples, such
as our partnership in the UK Biobank, a large-scale biomedical database and research resource,
and the inclusion of one of our medicines in the first value-based agreement under the Orphan
Drug Access Protocol (ODAP) process in the Netherlands.

Across the next decade, I also hope to see innovation everywhere. I think COVID-19 taught us
many things. It told us, for example, that care provision can take place at home – that medical
consultations via tools such as Zoom are feasible. We need to consider how these technologies
will evolve and how we will evolve with them to support patients and optimize our healthcare
resources.

What role do you think RNAi will play in that future?

Here, I’m not modest. I really hope that RNAi will be the field’s next big “future technology.”
The full potential of gene therapies still lies some way off because we don’t know enough about
their long-term consequences yet. Right now, we are at the start of an RNAi revolution. So far,
these therapies have only penetrated the liver, so don’t get me wrong – it’s clear that we are only
at the beginning. That said, at Alnylam, we already have a technology that can silence any gene
in the genome – and therein lies enormous potential. The next step will be successful penetration
of other tissues: the lungs, muscles, and central nervous system, to name a few. This will be our
greatest challenge, but I also believe it is the future. It’s a good reason to get excited!