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by myTomorrows myTomorrows | 23 Jun 2020

An Interview with Dr. James Shannon: How Scientific Discovery and Compassion for Patients Shaped His View of Expanded Access

Dr. James Shannon has a clear vision of how patients with unmet medical needs should be able to access drugs in development — and he keeps working to make it a reality.


Dr. Shannon, a member of the Royal College of Physicians, is chairman of the supervisory board of myTomorrows. Dr. Shannon retired from GlaxoSmithKline as Chief Medical Officer in 2015 and serves on the boards of several pharmaceutical companies.


Skilled at balancing the demands of regulators with the needs of patients, he played a key role in the evolution of Expanded Access Programs (EAPs). 


At Novartis, Dr. Shannon facilitated one of the first large-scale, global EAPs. The program provided Gleevec (imatinib) to more than 7,380 patients with chronic myeloid leukemia (CML) and acute lymphoblastic leukemia in 34 countries.


A Phase 1 Clinical Trial with impressive results prompted the launch of Phase 2 trials. Media coverage led to requests from patients to access the drug before approval. 


Dr. Shannon got letters from a patient group in Canada begging Novartis to accelerate development of the drug. He began corresponding with them.


“I remember the excitement of the patients when I was able to tell them that we were going to develop the drug,” he said. 


Clinical Trials and FDA Approval 

The Food and Drug Administration (FDA) told Novartis to do conventional Phase 2 and Phase 3 Clinical Trials.


“We were very much in a dilemma because we had great results, and we had the FDA telling us to take five years to develop this drug, while on the other hand, we had the clamoring from patients saying they wanted the drug tomorrow,” he said.


So Dr. Shannon went back to the FDA and requested permission to conduct expedited phase 2/3 Clinical Trials. At the same time, Novartis set up a large EAP to provide the drug to patients in places without trials. 

The program provided a successful framework for the development of global Expanded Access Programs.


Dr. Shannon recalled how they had to rapidly scale up manufacturing, while carefully balancing the EAP with Clinical Trials. 


“We needed to protect the Clinical Trials so that we could get results for the FDA,” he said. “We couldn’t jeopardize that, but at the same time, we believed it wasn’t right to withhold the drug from patients.”


The Cancer Drug that Changed Cancer Treatment

Gleevec (imatinib) was a landmark drug because it vastly improved outcomes of CML patients, and because scientific discoveries during its development helped establish a new group of drugs called targeted therapies.


Targeted therapies, which attack specific types of cancer cells with less harm to normal cells, have transformed cancer treatment.


This was the first time a consistent genetic abnormality was shown to cause cancer in humans.

Identifying the Philadelphia chromosome in patients with CML resulted in the discovery that the BCR-ABL tyrosine kinase causes CML. In turn, this led to the development of imatinib, which is a selective inhibitor of BCR-ABL tyrosine kinase. 


“Gleevec was at the forefront of targeted mechanisms,” Dr. Shannon said. 


An oncologist then asked to give the drug to a patient with metastatic Gastrointestinal stromal tumors (GISTs). GISTs are often caused by mutations in the KIT kinase, which have structural similarities with the BCR-ABL tyrosine kinases. Oncologists thought the tumors might respond to imatinib. They were right.


“I still have the scan results from that patient where you can see these tumors have disappeared,” Dr. Shannon said. 


This case led to Clinical Trials and imatinib becoming the first line therapy for metastatic GIST.


Listening to Patients and Their Families

These experiences shaped Dr. Shannon’s views about access to drugs in development, as did interactions with many patients and their families. 


An advocate whose husband had a degenerative disease told Dr. Shannon how a drug in development showed evidence of being beneficial for her husband’s condition, but a similar drug from another company had been withdrawn from the market due to liver side effects. 


“She said to me, ‘James, it’s not up to a government to tell patients what drug they are allowed to take. If a company gives us all the information about safety and efficacy, patients and their doctors should be able to decide to try a drug in development when they have no other options,’” he recalls. “That really summed it up in a nutshell for me.”


Challenges of Accessing Investigational Drugs 

Dr. Shannon has seen the structural barriers that patients face to accessing a novel drug: Finding out that a drug exists, obtaining information about it and navigating the system to access it, he said. 


Further, there is often a lack of knowledge among physicians. There are relatively few physicians who have substantial experience with Clinical Trials, and even fewer who are very familiar with Expanded Access, Dr. Shannon explained.

“You have this funnel where very few physicians and patients will know how to approach pharmaceutical companies to request access to novel drugs — and if they do, the answer will likely be ‘no,’” he said.  


Learning from Experience

On the other hand, Dr. Shannon understands the reluctance companies may have to embrace Expanded Access Programs. He notes that myTomorrows’ philosophy is to guide patients to Clinical Trials when available before considering Expanded Access.


As a pioneer of Expanded Access who has decades of experience in drug development, Dr. Shannon has some advice about clinical development strategy.


Firstly, he urges companies to remember that a patient seeking an EAP has no more options. 


“Why would you deny patients that chance?” Dr. Shannon said. “Be compassionate.”


Secondly, Dr. Shannon suggests companies should consider integrating EAPs into their clinical trial development strategy. EAPs present an important opportunity to collect Real-World Data (RWD).


Dr. Shannon recalls the case of a woman seeking access to a cancer drug for her son who didn’t qualify for a trial. She eventually got the drug.


“If she hadn’t been persistent and known how to navigate the system, her son would not have gotten the drug,” he said. “The mission of myTomorrows is to simplify that process by making information available to patients and their physicians and helping them navigate the bureaucracy in order to potentially access those drugs.”


Dr. Shannon expects EAPs to play an increasingly important role in drug development, especially in the approval process. Expanded Access can help regulators and physicians better understand a drug.


“The concern from regulators is that Clinical Trials are so tightly controlled that they don’t always accurately represent the patients who will actually get the drug,” Dr. Shannon said. “Real-world data from Expanded Access Programs also gives physicians more information when they are prescribing a drug.”


Third, take a proactive, progressive approach toward regulators and be less fearful of regulatory agencies. Regulators are frequently drafting guidance on innovative approaches of drug development, such as the inclusion of Real-world data.


Finally, Dr. Shannon recommends adopting a philosophy he was taught early in his career. 


“If you keep the patient at the forefront of your mind, you will keep doing the right thing,” he said.