Taking page from early AIDS activists, ALS patients push for access to experimental drug
Ron Leuty Reporter- San Francisco Business Times
A one-time tech security specialist, “Mike” now calls himself an amateur chemist and neurologist, seeking out new drugs to treat the deadly muscle-wasting disease known as amyotrophic lateral sclerosis.
It’s not a hobby; it’s his life.
Diagnosed in October 2013 with ALS — or Lou Gehrig’s disease — the 55-year-old Massachusetts resident believes he’s found hope in an experimental drug under development by a small Palo Alto company. Lab tests showed that Mike has the same makeup of biomarkers, or disease characteristics, as ALS patients who responded in a 2012 study of Neuraltus Pharmaceuticals Inc.’s drug.
If only Mike and other ALS patients could get “compassionate use” access to Neuraltus’ drug, they wouldn’t have to wait for a formal clinical trial to see if the compound slows ALS from progressively robbing them of the ability to walk, touch, swallow, speak and, finally, breathe. In the process, these one-person studies would help Neuraltus understand more about the drug.
There is the rub that exposes some of the cruel realities of the drug-development business: As Neuraltus plans to start a mid-stage study later this year, it literally and figuratively can’t afford to give away the drug to desperate patients in search of a ray of hope.
“If I were a patient, I’d be the same way,” Neuraltus CEO Rich Casey said. “I’d want to get the drug as soon as possible.”
Yet a grassroots band of ALS patients and caregivers — under the banner of Hope Now for ALS— are pressing Casey, the FDA and others, invoking a give-it-to-me-now strategy that AIDS activists used to win early access in the 1980s and 1990s to experimental HIV-fighting drugs. Ultimately, they hope to convince someone to cover Neuraltus’ costs for compassionate use or an expanded access program in parallel with a clinical trial.
“A large expanded access arm would benefit ALS research and help (patients),” Mike wrote in an email to Casey last month. “It is also important that long-term access to the drug should be ensured for those participants that benefit from it.”
It is, Mike admitted, an uphill battle.
“Big Pharma companies were sponsoring (HIV) clinical trials and provided stuff for free,” said Mike, who asked that his name not be used because his elderly parents don’t know about his ALS diagnosis. “With ALS, this is not happening because these are tiny biotech companies working on these (drugs). The big boys have been scared off by the disease and a 20-year history of failure.”
The ALS Association — the organization that last year raised close to $100 million via the “Ice Bucket Challenge” social media phenomenon— last month awarded a $1.5 million grant to help pay for a Phase II study led by Dr. Robert G. Miller at Sutter Health’s California Pacific Medical Center in San Francisco. Overall, the study will enroll 60 ALS patients in eight centers, Casey said, and privately held Neuraltus will contribute another $1.2 million or so.
It is a big step forward for a company with little cash and a promising drug, called NP-001.
But, in a way, patients like Mike may have stood a better chance of receiving NP-001 if Neuraltus wasn’t moving forward with its study. A well-controlled trial requires that researchers give the drug to some patients while others receive a placebo in order to provide as close to an apples-to-apples comparison to statistically quantify a drug’s safety and effectiveness.
“If everyone gets compassionate use, you wouldn’t want to go into a trial where you could get a placebo,” Casey said.
Various legislation has tried to find a work-around solution. The Goldwater Institute, for example, has pushed for “Right to Try” laws in various states, including California, but those are toothless because they can’t require a company to provide access to experimental drugs for terminally ill patients.
For now, companies must make a tough short-term decision, Casey said, with a longer-term benefit in mind.
“(Patients are) desperate and I can’t say, ‘OK, I’ll send you some drug,’ ” Casey said. “My first obligation is to develop NP-001 for all patients through a well-controlled study.”
Neuraltus’ latest trial, which could start enrolling patients in November and may produce data by this time next year, could lead to another Phase II study in about 300 patients. An even larger late-stage trial could set the stage for Food and Drug Administration approval. But that would be years away, assuming no scientific bumps along the way and Neuraltus lining up additional funding.
“We still have to prove the drug works,” Casey said.
The timeline doesn’t serve many of the roughly 400,000 ALS patients worldwide, including about 30,000 in the United States. About 5,000 people are diagnosed with the disease every year, and most will die within three to five years after diagnosis.
It has been a long, arduous road for ALS patients and Neuraltus.
For one, researchers haven’t even nailed down what causes ALS, let alone found a drug that can attack the disease rather than its symptoms. (South San Francisco’s Cytokinetics Inc., for example, is starting a Phase III trial focused on improving ALS patients’ breathing.) Many patients and researchers see NP-001 as one of the few compounds that could get to a root of the disease.
Researchers believe NP-001 works by regulating macrophages, a type of white blood cell that typically acts as the central nervous system’s garbage disposal by clearing away dead or damaged cells. In ALS, however, macrophages are thought to be stuck in the “on” position, causing inflammation that may contribute to the disease’s progression.
“This seems to be the only treatment that has shown promise,” said Mike’s wife, Alla. “The doctors don’t know if it’s safe enough, but there is nothing more dangerous than ALS. It doesn’t just kill you, but it takes everything from you that matters to you.”
The fact that five-person Neuraltus has been a one-product company with little to fall back on if NP-001 fails — and the drug’s potential intellectual property issues — is another red flag for potential investors. What’s more, many investors don’t have the patience to see Neuraltus through years of studies to confirm the biomarkers it saw in a subset of patients in its 2012 trial and followup studies.
Other companies haven’t helped, either. Trial failures in ALS and Alzheimer’s, for example, have made venture capital firms and other investors wary to pony up cash for another experimental neurological drug.
Even other companies’ supposed successes can pose problems. For example, some ALS patients this spring pushed the FDA to accelerate approval of a drug from a mom-and-pop Pasadena company, called Genervon Biopharmaceuticals LLC, after a 12-patient study seemed to indicate that patients who received the drug could swallow milliliters more liquid.
Genervon hadn’t actually filed for accelerated approval, though, and the FDA hasn’t budged without more evidence of the drug’s safety and efficacy for ALS patients. Still, a Change.org petition, urging the agency to approve Genervon’s drug, has collected nearly 800,000 signatures.
Girded by that social media success, members of Hope Now for ALS started firing off form letters to Casey, the ALS Association and the FDA. Their pleas aren’t falling on deaf ears, Casey said.
Still, clinical trials cost millions of dollars — Neuraltus’ potential 300-patient mid-stage study, for example, could cost as much as $30 million — and there is little room for error over the five to 10 years a drug is in development.
That is time that Mike and other ALS patients don’t have to give.
“If someone told me to chain myself to the FDA tomorrow, I’d do it. But just going by myself is not going to do it,” said Alla, Mike’s wife.
“We have a good life together and we’re trying to hold on to what we have now,” she said. “And every day it gets worse.”