When his father was diagnosed with a serious, difficult to treat lung cancer, Ronald Brus should have been the last person to feel helpless.
Brus is a medical doctor and a long-time executive in Europe’s pharmaceutical and biotech industry. Although he quickly learned about a promising experimental drug to treat the cancer, after six months, he still hadn’t received the legal go-ahead for his father to get the treatment, which regulators hadn’t yet approved for sale. The exemption almost came, but then it was too late. His father died in the Netherlands at the end of 2012.
“The evidence was there that the drugs worked quite well, but it was almost impossible to get a hold of them, even for me,” Brus says.
The ethics and practicalities of making unproven drugs available to very sick patients have always been controversial, but now–when anyone can go online and learn about experimental drugs that seem like the thing that might save them or their family member–the issue is especially fraught.
The 2013 Academy Award-winning Dallas Buyers Club, a movie about an AIDS patient who smuggled experimental treatments into the U.S. in the 1980s, highlighted these issues, as has the ongoing Ebola epidemic centered in West Africa. For example, ZMapp, one promising Ebola drug in development that had only previously been tested in monkeys, may have helped a handful of people who survived, but only a few doses were available. But in Sierra Leone, the use of another experimental Ebola drug, which had not even been tested in animals, prompted a group of U.K. doctors to walk out of a clinic over safety fears.
Ebola and AIDS are both worldwide public health emergencies, but when a loved one is dying, families experience the same emergencies on a personal level–and the same urgency to find a cure. Online, they may find many drugs that aren’t on the market yet: In the U.S., it often takes a decade or longer for a treatment to wind through human clinical trials required for FDA approval, which unfold in several stages that first test the safety and side effects in patients and only later examine the treatment’s efficacy. However, while news articles, animal research studies, and press releases may indicate promise, many drugs and treatments fail at some stage and never ultimately reach FDA approval.
In the red tape he experienced with his own father, Brus saw a classic opportunity for a startup that would get promising experimental drugs to patients in need and help them quickly navigate the processing paperwork. The Dutch startup he founded, called myTomorrows, is only operating in Europe and Turkey for now, with investments from Balderton Capital and life sciences firm Sofinnova Partners. So far, Brus says, it’s helped “hundreds” of patients who have diseases ranging from cancer to central nervous system disorders access drugs.
Today, both the FDA and Europe’s EMA allow for compassionate use exemptions, case-by-case decisions that allow companies to give early-stage drugs to very ill or dying people who live too far away, are too sick, or otherwise wouldn’t qualify to participate in a clinical trial. But the FDA only gets about 1,000 to 1,200 applications a year. Not many patients have the resources or high-quality doctors to learn about drugs in development, and as Brus learned in Europe, even then it isn’t easy. Also, getting approval isn’t enough: The government’s clearance doesn’t require a drug company to supply an experimental drug–that is entirely up to the company.
myTomorrows works by negotiating directly with drug developers for access to promising treatments, compiling accurate data on the drug’s risks and successes to date, streamlining the application paperwork, and later receiving data on the use of the drug. It aims to provide a one-stop shop for desperate patients seeking options, as well as biotech and pharmaceutical companies that are too short-staffed to deal with requests from sick patients or want to hold the whole process at arms-length. The startup’s lawyers have spent three years weeding through the specific laws in each European nation. “We do all the paperwork in basically an automated fashion,” says Brus.
One example is the company’s work with the U.K. pharmaceutical company Syntropharma, which has developed a skin patch for treating patients with severe depression who don’t respond to conventional drugs. myTomorrow’s model is to become the exclusive provider of the patch to patients who need it before all of the clinical trials are complete. It charges patients (or their insurance providers) a fee to cover the costs of the medicine and the processing and paperwork. But because it is collecting useful early patient data for the drug developer on a large population, the bulk of its profit would come later, though a small royalty on sales of the drug once it’s approved.
“It can take 15 years for a drug to be approved, but maybe after eight years, there’s pretty good evidence that a drug does work or doesn’t work,” Brus says. “We believe it’s unethical not to give the patients that drug.”
The flipside, of course, is that there’s a reason for regulatory review–an experimental drug is riskier and may not work, offering false hope to a dying person.
Brus and his colleagues aren’t the only people pushing to ease restrictions to early-stage drugs. In the U.S., the libertarian Goldwater Institute is lobbying to pass “Right To Try” legislation in all 50 states that would give doctors the “ok” to prescribe terminally-ill patients unapproved drugs that have undergone minimum basic safety testing. In the last year or so, it’s succeeded in passing bills in five states: Colorado, Arizona, Louisiana, Michigan, and Missouri. Still, these bills might not change much, says Alison Bateman-House, a researcher who specializes in compassionate use at NYU’s Department of Medical Ethics: The FDA has ultimate authority and could still require patients apply to individually for exemptions.
Bateman-House says “Right to Try” legislation is mostly offering patients “smoke and mirrors,” because a doctor’s ability to prescribe unapproved drugs or his willingness to do paperwork usually isn’t the main reason most patients can’t access experimental treatments. Often, she says, it’s the drug companies that don’t want to distribute their trial-stage treatments. The laws do nothing to change this, she says.
As it stands, drug companies have very good reason for withholding: the fear of compromising their clinical trials and ultimate approval of the drug. If a patient has a bad outcome outside of the controlled environment of a clinical trial, companies fear that regulators will balk. However, while that’s a good thing if the drug is truly dangerous, it may also be that the patient was just too sick to be saved. This is not an abstract fear. In November, the FDA halted trials of a cancer drug because a compassionate use patient died.
“People like myTomorrows, and people who are in favor of Right To Try laws, they think these are terminally ill patients who have nothing to lose. And as a red-blooded American, I think that makes sense. But that’s only one part of the equation. The thing that people don’t talk about is getting these drugs available to the rest of the world,” she says. In other words, anything that slows or compromises the clinical trial process could hurt everyone else who doesn’t have early access. “What they do has ramifications for other people,” she says.
One company, at least, is actively inviting dying patients to test its experimental therapy in a radical way. The Maryland company, Neuralstem, is developing a stem cell therapy for ALS patients, a diagnosis that usually only gives patients a few years to live.
CEO Richard Garr, who is an active proponent of the Right To Try laws and is working with the Goldwater Institute on their campaign, says patients in states that have passed the laws can try the therapy. The hard part, however, will be finding hospitals willing to do it: The treatment is not a pill, but a surgery. Delivering the stem cells involves the world’s first-ever injections directly into the spine, according to Garr, and the company would have to specially train surgeons to perform it. So far, under the auspices of formal Phase 1 and Phase 2 clinical trials, the company has successfully supervised about 36 surgeries at three hospitals around the country, he says. Its Phase 2 data, which tests for efficacy in a small number of patients, will be published in January.
“Compassionate use is a one-time process, and there are 5,000 to 6,000 new ALS diagnoses a year. [The process] wasn’t built to handle large numbers,” Garr says. He says Neuralstem doesn’t plan to be a “rogue company,” and that he is hoping the FDA will allow ALS patients in Right To Try states access to the surgery. Still many questions would need to be worked out first, not limited to what (if anything) to charge, how insurance reimbursement would work and who would be liable if something went wrong.
At myTomorrows, Brus believes that both the U.S. and European laws will eventually become more flexible as more patients and doctors hear about innovative new treatments in a more connected world. This will become especially true as medicine becomes more personalized.
Bateman-House agrees, but she says the key will be getting regulators and companies to work together to improve and equalize access to early-stage treatments in a way that doesn’t jeopardize the more formal evaluation process. “[Right now], if you’re going to a city clinic and you have 15 minutes with a doctor, you’re not going to get access to an experimental drug,” she says.
The original headline of this article was changed to reflect the fact that the movie, Dallas Buyers Club, was about a true story.