Into the trial process

We have not spoken in much detail about progress toward drug trials, having referenced them in our launch of this site, so I want to first cover some basic information on how they operate as pretext for what we are doing. There has been a lot of expectation and some disappointment, so we want to share confirmed news.

To gain approval for a new drug, a pharmaceutical company progresses into human testing in a three step process called "phases". Phase I examines the drug's safety. Phase II moves out from an evaluation of safety into effectiveness or efficacy, usually with a placebo group that is masked from participants and observers. And Phase III is a wider examination of efficacy that evaluates more refined dosage studies with an eye toward interaction with existing therapeutics.

Because of the urgency created by ALS progression, trials rarely go wanting for participants. It may be a little arcane to discuss the calculus of how/why we decide to enter a trial (some exclude use of unapproved drugs while on trial, certain trials require the medication to be taken by infusion or by mouth only, etc.), and trials involve some sacrifice of time and freedom even though they are balanced with hope. There are two reasons we have been working with the Healey Center. First, it is a multi-disciplinary, integrated care team; and this means we usually see the full cohort of physicians, therapists, nurses and counselors when we are in Boston. Second, and directly related to novel therapeutics, it is a research center that has several physicians actively working with leading pharmaceutical companies, both mature and early-stage, to enroll and study patients in the pursuit of viable therapies. Our primary neurologist is Dr. Katherine Nicholson, most often referred to as Katie, and she is in direct contact with Deb concerning recommended trials based on a variety of factors. Currently only three drugs are approved by the FDA for the treatment of ALS, and Deb is on the two that address her specific condition, one in an oral suspension and the other by monthly ten-day infusion cycles. Any trials under consideration take the current regimen into account.

RAPA 501 is an autologous t-regulatory cell treatment (Tregs), so described because Deb's cells were removed several weeks ago by Apheresis, a multi-hour process where blood is circulated through a machine and separated into its component parts for further study. Abbey accompanied Deb to Boston for an overnight trip when she was visiting from Chicago, and the Apheresis essentially made three "round-trips" of Deb's blood through this machine, requiring several hours. Tregs are part of the immune response regulation system, and the goal is to determine whether these cells can arrest the cell mechanism that causes ALS to progress in its destruction of muscle cells (This is a simplified description based on my lack of scientific background, more can be found on the RAPA website.). RAPA 501 is a study that originated with research by Dr. Stanley H. Appel at Houston Methodist, one of the foremost medical centers for the treatment of ALS, and Deb is under the care of Dr. James D. Berry at the Healey Center for this particular trial.

The RAPA trial is administered by infusion. Deb's cells were sent to RAPA Pharmaceutical where they were integrated with the therapeutic and multiplied with the goal of autologous (essentially getting your own cells back) reintroduction by infusion. That's what we did on Tuesday of this week. Because of the complexity of this trial, it introduced us to an array of "chain of control" sign-offs by physicians and nurses with the infusion arriving in a cryopak container that maintained the Tregs at a mind-boggling -175 degrees celsius until infused on Tuesday. On Wednesday, a post-infusion blood draw was completed back at the Healey Center, and we will be returning on Day 8 and Day 28, eventually completing three more four-week cycles. A study like this can only be administered on the research floor at MGH, known as White 12. It feels like a hospital floor influenced by a lab, and the nursing staff operates in the specialized world of highly-controlled drug handling and evaluation. During the infusion, Deb was in a private room and I ferried Starbucks and otherwise made myself busy. Because RAPA is used to treat other conditions, there is no placebo or control group.

After all of this rather sterile description of a drug trial, the question is "Why?", so here is an attempt to put you in the shoes of an ALS patient. First, therapies are numbered and none of these currently stop ALS progression but are meant to slow its progression (25% reduction in progression is considered viable). In all of these drugs, there is cumulative benefit being seen, and that is why patients will go on multiple treatments. Second, time comes at you differently with ALS. I have talked about this in other posts, but with a time-bound opportunity to work within this disease you tackle as many avenues as you feel are reasonable and still preserve quality of life/mobility. Finally, you cannot be in this fight and not think about how you can contribute to the advancement of knowledge around ALS. As the medical field's understanding of the cell mechanics increases, targeting therapies becomes more sophisticated and successful. We look at drug trials as a combination of these things but also as a way to "pay it forward" just as we are in the early stages of thinking about sharing our financial resources into the cause beyond annual gifts to Healey. I could write an entire post on the interaction of medical professionals, philanthropy, venture funding for drug discovery, and patients. While no one can be blind to the inefficiencies of so many endeavors in this world, it is both humbling and engenders a certain amount of awe for the way in which human discovery necessarily comes from a complex web of individuals pursuing self-interest that ultimately yield wider benefits.

We are so hopeful about this process, and the medical team who supports us, so I thought it would be helpful to do a quick blog. We are also doing things outside of pharmacology and will share it in a future post.

SPECIAL NOTE: On Sunday, April 11, we received the heartbreaking news that Deb's father passed away that morning. As someone who remained committed to his beloved White Mountains and had just completed a winter hike with Deb's brother, Bill, in December, we were unprepared and are still in shock. A. Richard Murphy (known by friends as Dick and by his grandchildren as Grandpa) was a steady and steadying influence over his family, having worked throughout his career with IBM, rising to Head of Personnel for Asia/Pacific and retiring as Head of Human Resources for Lexmark, taking the IBM spinout public through a public offering before retiring to spend time with Mimi back in Contoocook, NH were he became an avid painter. He and Mimi became the oldest couple to join the "4,000 Foot Club", climbing the 48 New Hampshire peaks over the course of a life lived to the fullest. We miss him dearly.