What can the rare disease community as a whole learn from advances made in cancer therapies?
At the National Organization of Rare Diseases’ annual Rare Diseases & Orphan Products Breakthrough Summit (NORD Summit
) held in Washington, DC, a panel of experts sought to explore the question further.
Among those involved in the discussion were Richard Pazdur, MD, director of the US Food and Drug Administration’s (FDA’s) Oncology Center of Excellence (OCE); Deborah Morosini, MD, MSW, vice president of clinical affairs and patient engagement at Loxo Oncology; Ellen Sigal, PhD, the founder and chairperson of Friends of Cancer Research; and Samit Hirawat, MD, executive vice president and head of oncology global development at Novartis.
In their discussion, the group of presenters reflected on the history of cancer therapies—pointing out past and current shortcomings as well as the success experienced in oncology space—in an effort to identify how the successes of these treatments and the principles adopted by the oncology community can be applied to other diseases. Their discussion homed in on important topics such as patient advocacy, clinical trials, and genomic data.
More than 40% of orphan drugs approved by the FDA and about 40% of all drugs in development are for rare types of cancer. Dr. Pazdur added that advances in targeted therapies and immunotherapies in particular have drastically changed the treatment landscape.
“Those [scientific advances] are the underpinnings that make everyone’s life easier,” he said.
However, Dr. Pazdur also acknowledged that he faced a number of challenges in oncology back in 1978 and 1979. According to him, it was a time when drug development for cancer was not an interest of biopharmaceutical companies and nearly all treatments were so toxic they sometimes assisted in their patients’ deaths.
Dr. Morosini added that the biggest issue stopping pharmaceutical companies 20 years ago may very well have been the toxic side effects and off-target effects of therapies in development. Essentially, the lack of risk reduction served as a major deterrent.
“I really thought pharma would have very little interest in [cancer therapies] since the drugs were overly toxic and people in the 70’s did not even want to talk about cancer,” Dr. Pazdur said. “It was very hush-hush; oncology had this sort of shroud around it. But I could not be more wrong.”
However, Sigal stressed that patients made a huge difference. “They wanted a seat at the table and became the best advocates,” she said. Translating science so that it is meaningful to the patient has been pivotal, she added, and good leadership that has made an effort to listen to patients has made all the difference.
Dr. Morosini also pointed out that the cancer genomics that have become more widely available have really changed the turf as they have established cancer as a genomic disease. “That was pivotal,” she said.
Collectively, the panel noted that one of the remarkable moves that occurred in oncology was the shifted mindset and structure in the clinical trials, which are mostly performed by community centers today—not academic medical centers.
With so many therapies being evaluated in clinical trials in 2018, Dr. Pazdur and the panel suggested that adjusting clinical trials so that they follow a “real-time oncology review” would be in the best interest for cancer patients, as denying someone a drug can be just as harmful as giving someone a drug that may not be “the greatest.”
The panel also noted that conducting randomized trials are becoming increasingly difficult to do as cancer treatments segue into rare diseases. Due to small patient populations—which is common in rare disease trials—a randomized study can often be difficult to perform. Additionally, trials comparing therapies that are 40% or 50% effective with therapies that are 5% effective are unrealistic as patients will not want to enroll—especially if the trials are not corssover trials.
While the panel acknowledges the importance and need for survival advantage measures in clinical trials, in addition to measuring endpoints, they also stressed the importance of paying attention to efficacy, safety, and response rates since survival studies can be difficult to conduct with such small patient populations.
As long as the trials are well-conducted and there is integrity and long-term follow-up, good measures can be taken. However, the team noted these sorts of changes in the clinical trial process are not ones that will happen overnight and without extensive research and discussion.
Concern over strict, long-term guidelines for clinical trials also raised the concern of failing to get patients the therapies they need in the time that they need them.
“Clinical trials are important, but not all clinical trials are equal,” said Sigal. “We have to do better and do smarter clinical trials.”
To date, groups of people—such as those in Africa and in Hispanic nations—are still underrepresented in clinical trials and data, according to Dr. Pazdur; to address this issue, the panel stressed the importance of including as diverse a population as possible in clinical trials evaluating new therapies.
Switching to current challenges being faced in cancer drug development, the panel noted the concern of biopharmaceutical companies crowding to one therapeutic approach, such as PD-1 inhibitors.
Especially in the age of genomics, if specific genomic targets can be identified in a cancer that will not benefit from therapies known to target other identified targets, having too much of one type of therapy could be ineffective. For example, patients with identified, specific genomic targets will likely not benefit from therapies known to treat other identified targets.
When comparing cancers and rare diseases, the panel noted the disparity in genomic data between the 2 groups. For example, while patients with cystic fibrosis are mostly all genomically tested, that is not the same case for cancer patients.
“Genomic testing is not all the same—and that’s an issue,” Sigal stressed.
With such a wide variety of genomic tests, the panel acknowledged the potential gaps between different tests of varying quality. They also noted that unlocking more genomic data is an area for improvement in cancer patient populations. Rare diseases are already off to the races with trying to generate genetic data as nearly 80% of rare disease have a genetic basis.
Summing up the connection linking cancer therapies to rare disease therapies, Dr. Pazdur circled back to the main point to address in both fields since the connections are still not completely clear. “The real issue is what questions need to be answered and how do we prioritize those questions?” he closed.