Meet the Experts: Dr. Doron Sagman

Dr. Doron Sagman

Dr. Doron Sagman is Lilly Canada’s Vice President of R&D and Medical Affairs as well as Lilly’s Senior Medical Director. Doron is a physician with nearly 20 years of experience in the pharmaceutical industry spanning many therapeutic areas, including mental health, diabetes, oncology, autoimmunity, neurodegeneration and pain. He spoke with IMC about the mechanisms of action showing the most promise as avenues to effectively treat people with COVID-19.

What are the leading pharmacological approaches that are being researched for the treatment or prevention of COVID-19?

There are four big categories of medicines that are being tested.

Powerful immunomodulators, of the kind used to treat autoimmune diseases like rheumatoid arthritis, are being tested in patients who have been hospitalized for COVID-19. These patients are experiencing the most acute symptoms of the disease, up to and including Acute Respiratory Distress Syndrome (ARDS), which is often fatal. The current theory is that by dampening the amplified immune response in affected individuals—the so-called ‘cytokine storm’—these medicines will reduce the severity of the disease and thus reduce mortality.

Antivirals are being developed to slow or halt the replication of the virus in the sick person’s body. By reducing viral replication, antivirals reduce the amount of time it takes a person to recover.

Antibodies are proteins that the body produces in response to antigens, of which viruses are one kind. Many companies, including Lilly, are developing antibodies as potential medicines. In this work, researchers take blood samples from people who have recovered from COVID-19, and screen them to find—from among the hundreds of millions of antibodies present—the antibodies that show the most promise in potentially fighting the coronavirus. These neutralizing antibodies block the targeted virus from attaching to and entering healthy human cells. In theory, this may prevent the virus from using the host cell to replicate, which is what spreads the infection and increases the body’s inflammatory response. Antibodies may also potentially speed the immune system’s work in clearing the body of active virus, to help the person recover more quickly.

Vaccines are the best-known class of medicines being developed against this virus. Vaccines train a person’s own immune system to recognize and fight a particular virus or bacteria; they trigger the immune system to make its own antibodies against the infection. This is the basis of all vaccines, including the yearly flu shot. Currently there are dozens of vaccines in development.

The breadth of the research and the pace of this pharmaceutical development are unprecedented, but before any of these potential medicines can be incorporated into widespread use for COVID-19, the molecule will need to have been proved effective and safe.

How will the eventual availability of a vaccine impact the need for these other kinds of therapies?

We expect antivirals and anti-inflammatories that can safely prevent the worst symptoms of the disease will continue to have a role to play. Likewise, we see a potential role for antibody therapies after a vaccine is available. For example, certain populations may choose not to get vaccinated, or they may not be able to get vaccinated, due to issues like a compromised immune system, an underlying chronic disease, or they may be of an older age at which people typically don’t respond as robustly to vaccination. The eventual toolbox for treating and preventing COVID-19 will likely hold many different medicines for different aspects of the disease.

What can we learn from the example of hydroxychloroquine, which was touted as having great potential and has now been shown to do more harm than good?

The threat from COVID-19 is so urgent, and so important, that we’re seeing all sorts of ideas being suggested, with hundreds of theories being tested. Positive results get media coverage because they give people hope, but when the experiments are small or the methodology unsound, their results are unreliable, and might ultimately be disproven through more robust research. This trend isn’t exclusive to the coronavirus, either. We often see headlines about researchers who appear to be on the path towards a cure for some type of cancer, for example, when the article underneath it tells the story of research results produced only in mice.

This is all a great reminder of the importance of research rigour, with large trials that are designed and powered to deliver statistically significant results. It’s extraordinary and inspiring to see so much research activity focused on this one medical need. However, media coverage of ideas that turn out to be dead ends illustrates the inherent challenge of pharmaceutical research, and the resource-intensity of developing a molecule all the way from a theory to a new medicine that’s approved for human use. It’s an enormously complex process, and the complexity doesn’t always come across in the media coverage.

Lilly’s Global Medical Director, Dan Skovronsky, told Reuters that Lilly’s antibody, if it works, could be approved as early as this fall, after being isolated just this past spring. How does this compare to usual timelines for developing and launching a new medicine?

It usually takes 8-12 years for a molecule to be identified, assessed for its safety and tolerability, and run through three phases of rigorous clinical trials, which often have thousands of participants to increase the precision of the resulting data on efficacy and safety. With the coronavirus, we don’t have 8 years. Millions of people are getting ill, hundreds of thousands of people are dying, and our global economy is suffering, which is hurting people too. The spread is not slowing down just because we think it’s time that it should. We need to find solutions quickly, and the pharmaceutical industry is pouring everything we have into wrestling this virus into submission.

I’m proud to be a part of this innovative industry. I’m awed—but not surprised—by the progress that has been made in such a short amount of time by highly skilled and dedicated scientific teams, and I’m optimistic that we’ll have effective treatments or preventatives available in the near future.


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