What ALS Can Learn from the Cancer Experience: The American Public Can be a Powerful Change Agent

“You must be the change you wish to see in the world.” - Mahatma Gandhi  

The Cancer Experience teaches us that the American Public can be a powerful change agent.  Recall, Dr. Slayman from the UCLA Medical Center who became a powerful change agent when he convinced Genentech (San Francisco, CA, USA) to fill out a clinical trial application for the cancer therapy, Herceptin (see post: What ALS Can Learn from the Cancer Experience: Identify and Support Champions and Change Agents)?  Well the story doesn’t end there.   

Before Genentech could start Phase 2 clinical trials, its Phase 1 success was highly publicized in the media.  Soon, Genentech phone lines and mailboxes were inundated with calls and letters from women wanting the drug under Expanded Access.  The company flat out refused.  They wanted to focus efforts on enrolling people for the clinical trials and were nervous that widespread access would halt the clinical trial process.

A young gynecologist by the name of Marti Nelson had recurrent breast cancer and wanted to participate in the Herceptin clinical trials, but was repeatedly denied.  In response to her death in 1994, thousands of activists stormed Genentech.  They decided to hold a funeral procession for Marti Nelson right in front of Genentech headquarters.  They chained themselves to the doors, and pounded on the doors for Expanded Access.  All in plain view of the media.             

Pressure built and in 1995, Genentech arranged talks with the breast cancer advocates.  The company decided to provide Herceptin to small numbers of women outside of clinical trial on a basis of a Drug Lottery.  A true success story for cancer advocates. 

The Ice Bucket Challenge, Steve Gleason Act of 2015, and policy change advocates who will be in Washington D.C. this May is an astounding testament to the power of the ALS Community.  Now is the time to think BIG, and demand policy form that will result in treatment options for those suffering with ALS who do not qualify to participate in clinical trials.  Thanks to the HIV and Cancer Movements, the U.S. FDA already has programs in place to fast-track and offer treatments outside of clinical trial.  The U.S. FDA approves nearly all applications for Expanded Access.  Now’s the time to advocate for the Marti Nelsons of the ALS Community.  Demand that your policy makers remove barriers and provide incentives to the companies to offer Group and Widespread Expanded Access Programs for promising experimental drugs, therapies, and devices.

What ALS Can Learn from the Cancer Experience: Bypassing Clinical Trials, A Cautionary Tale

Dr. Siddhartha Mukherjee’s, author of the book, The Emperor of all Maladies: A Biography of Cancer in the PBS Documentary said, “Medicine being the most humane science…sometimes scientists are caught doing inhumane things which is denying experimental drugs.  However, putting a drug on the market too early has had historically devastating events.” 

What Mukherjee is referring to is the consequences of releasing an experimental drug or treatment via Accerlated Access before Phase 3 clinical trials have been undertaken.  An example of this is the STAMP treatment for breast cancer in the 1980s and 1990s.

In 1983, Dr. Peters and Dr. Frei started breast cancer clinical trials on a new therapy previously shown to have some success at treating childhood leukemia, known as the Solid Tumor Autologous Marrow Program (STAMP).  STAMP involved extracting bone marrow from the participant and freezing it, then wiping out their cancer with extremely high doses of chemotherapy, and injecting the bone marrow back into the person so that the high-dose chemotherapy wouldn’t kill them.  Promising success in Phase 1 and 2 clinical trials with breast cancer patients encouraged women who could not participate in the trials to seek accelerated approval of the treatment.  Soon 30,000 some women received access to the experimental therapy between 1985 and 1998 at the cost of millions of dollars.  The study could not recruit people for the Phase 3 clinical trials because no one wanted to be in the control group.  About 1 in 5 women died from the treatment and it was later shown that the higher dose of chemotherapy was not any more successful than the lower doses in improving women’s survival.  And in fact there was a higher chance of death due to the bone marrow implants.  Those who did survive the procedure suffered long term cognitive problems such as short term memory loss.     

    

Some of you might still be asking yourselves, so what’s the big deal?  The women at least got a chance to try something?  The big deal is that an experimental treatment that has not gone through the full round of required clinical trials carries a higher risk of actually shortening the person’s life if not killing them.  Perhaps someone who is near the tail end of their disease is willing to take this risk, but what if you are someone who is early on in their disease?  By foregoing clinical trials you risk shortened lifespan, death, and the right to try other treatments that might become available.  That’s right, clinical trials have strict inclusion and exclusion criteria.  Meaning, in order for the researchers to know without a doubt that their treatment is having an effect, they cannot allow anyone into the trial that has taken other experimental drugs.  Moreover, what if a drug is approved for Accelerated Access and a large number of people start taking the drug and suddenly have major toxic reactions or die.  Even if this is unrelated to the treatment itself, such an event might trigger the FDA to remove the treatment from the market altogether…that’s it.  A possible beneficial treatment to some people with ALS will never reach them.        

  

I’m not saying we should not seek treatments through Accelerated Access period. I’m simply saying there is a time and place.  The U.S. FDA Evaluation team is in place to insure consumer safety.  If companies can satisfy their requirements that show scientifically that their treatment warrants Accelerated Access based on evidence that is safe and efficacious than this is a good thing.  If not, we should consider other options for treatments outside clinical trials such as Widespread and Group Expanded Access, which is politically more kosher with the U.S. FDA and doesn’t hinder the clinical trial process. 

On May 10, let’s ask our policy-makers to work with ALS advocates, pharmaceutical and biotechnology companies, the Centers for Medicare and Medicaid Services and the U.S. FDA to remove barriers for companies to offer Expanded Access to People with ALS.

What ALS Can Learn from the Cancer Experience: To Move Forward We Must Look Back

To move forward, we need to reflect on the past.  The Spanish philosopher, essayist, poet and novelist George Santayana once famously said, “Those who cannot remember the past are condemned to repeat it.”  Not knowing your history can indeed have devastating consequences both in repeating mistakes but also not capitalizing on opportunities.

 

The Cancer Experience teaches us that developing successful treatments is not easy.  There are a lot of hurdles that must be overcome including technological, financial, political and socio-cultural.  Complicated diseases need a full-forced commitment of funding and political will.  It took decades, billions of dollars, and strong political commitment to fund cancer scientists and medical doctors whose research efforts helped lay the foundation for advancements in medical procedures, radiation therapy, chemotherapies, hormone and immune therapies that we benefit from today.     

This was made possible through huge financial investments not just from private donations, but also sizable public funding.  Mary Lasker and Dr. Sidney Farber spearheaded the private-public funding effort in the 1960s, which resulted in enactment of the 1971 Cancer Act, and billions of dollars in funding towards the National Cancer Institute.  The Ice Bucket Challenge was a major breakthrough in private funding for research, now we need equal commitment for public funding to support non-profit universities, teaching hospitals, institutes and government agencies.  Places such as the Robert Packard Center for ALS Research at Johns Hopkins, National Institutes of Neurological Disorders and Stroke, and ALS Treatment Development Institute. 

The Cancer Experience teaches us that it is important for grant dollars to be flexible and support a diverse workforce of researchers.  The most innovative, game changing cancer therapies came from the minds of new doctors and researchers in the field, people with fresh eyes, willing to take more risks and think out of the box.  People like Dr. Bernard Fisher who in 1958 went against an almost 70 year practice of the radical mastectomy and proved through randomized control trials that women who underwent breast conserving surgery also known as the lumpectomy had the same survival rates as women who underwent a radical mastectomy.  People like Dr. Sidney Farber who in 1947 went against the medical community by giving children suffering with leukemia the experimental chemotherapeutic, aminopterin.  The standard at the time was to make children comfortable until their inevitable death.  Aminopterin allowed some of the children to go into remission.  Had these medical renegades not been hired and given resources, evidence-based practices would not have been developed, advancements in treatment would have been lost.

Today, the lack of research dollars for the biomedical sciences has stymied advancements.  In order for new scientists and medical doctors to even be considered in the applicant pool of 300 or more people vying for the same job, they must already have funding.  To get funding, scientists and medical doctors must be affiliated with a university or a government facility.  A catch-22 occurs, resulting in small numbers of scientists and medical doctors, experienced but not necessarily game-changers; all competing for finite resources.  A substantial amount of grants require a significant amount of preliminary data generated by the Principal Investigator (lead scientist) and proof of success.  Therefore, high-risk projects that may challenge current paradigms or lead to new therapeutics are less likely to be funded compared to “inside the box” ideas.  The ALS Community must identify the Dr. Sidney Farbers and Mary Laskers and pave the way for real commitment through policy change and private-public funding.

What ALS Can Learn from the Cancer Experience: Introduction

It was 1969 and President Nixon declared a War on Cancer.  Despite being in the midst of a recession caused by the Vietnam War, billions of dollars were poured into cancer research and a new era in cancer’s history started.  Cancer was once a disease scientists knew little about, a disease no one wanted to discuss became a national priority.

This change didn’t come about suddenly.  As a field of science it has span time in memoriam, from early Egyptian papyrus that documented some of the earliest cases of breast cancer, to the invention of early treatments such as the radical mastectomy and radiation therapy of the 1890s, to the diverse chemotherapies, hormone therapy and immune therapy of today.  This success story has multiple heroes.  First there were the dedicated scientists with an insatiable appetite for discovery, conviction to eliminate human suffering, and defiance against the status quo.  Next on the scene were the entrepreneurs and visionaries that spearheaded private and public funding efforts, followed by American citizens who both suffered from the disease and watched their friends and family members die of the disease until a boiling point was reached and they said ‘We’re not going to take it anymore.”

The history, science, medicine, and politics of cancer were beautifully summarized in Siddhartha Mukherjee’s book, The Emperor of all Maladies: A Biography of Cancer, recently turned into a PBS documentary film by Director Ken Burns.  Most striking about this film is the parallels to other major diseases and public health funded projects in U.S. history; parallels that the ALS/MND Community can learn from and apply to advance ALS science, treatments, and access to experimental drugs and therapies outside of clinical trials.  

This post is one of a five part series on lessons learned from The Cancer Experience:

• Introduction
• To Move Forward We Must Look Back
• Identifyand Support Champions and Change Agents
• Bypassing Clinical Trials, A Cautionary Tale
• American Public Can be a Powerful Change Agent