Ionis Pharmaceuticals, Inc. (formerly Isis
Pharmaceuticals) has achieved another milestone in its search for a treatment
for Huntington’s disease: on January 5 the company announced that the U.S. Food
and Drug Administration (FDA) granted Orphan Drug Designation for its gene-silencing drug, currently under study in a clinical trial in
Europe and Canada.
The FDA designation, intended to facilitate development of the
test drug IONIS-HTTRx by
offering financial incentives and assistance, could not come at a better time.
Huntington’s disease patients – like 18-year-old Terry Leach of San Diego, who
died the morning of January 2 – continue to succumb to this devastating,
untreatable disorder.
“Although the toxic protein produced from the huntingtin (HTT)
gene in HD patients has been a target of interest for many years, IONIS-HTTRx
is the first therapy to enter clinical development that is designed to treat
the underlying cause of this fatal disease,” Frank Bennett, Ph.D., Ionis’s
senior vice president of research, said in a company press release.
“The granting of Orphan Drug Designation in both the U.S. and Europe highlights
the significant need for a drug that could transform the treatment of HD.”
HD-affected Phase I clinical trial volunteers in London received
the first dosing of IONIS-HTTRx
in the October 2015 (click here to read more). IONIS-HTTRx could potentially reduce, partly reverse, and even prevent symptoms.
Likely ending in 2017, Phase I is testing primarily for safety
and tolerability. If it is successful, Phase II and III trials measuring the
drug efficacy’s would ensue. Together the three phases of a trial typically take at
least five years. If the trial is successful, a drug could become available
around 2020.
Frank Bennett, Ph.D. (photo by Dr. Ed Wild)
Increased dialogue, helpful benefits
“We were pretty excited to get Orphan Drug Designation,” Kristina
Bowyer, Ionis’s executive director of patient advocacy, said in a phone
interview on January 5. Ionis is based in Carlsbad, CA.
The designation means that the FDA recognizes “the severity of
the disease and the limited population,” she noted.
The designation creates an opportunity for increased dialogue
between Ionis and the FDA regarding the IONIS-HTTRx clinical trial,
Bowyer explained.
Such extra communication
can help resolve the unique issues of orphan disease trials. Because an
orphan disease like HD involves fewer than 200,000 patients and very
specific approaches to treatments, the design of clinical trials is atypical,
Bowyer said. The smaller number of potential volunteers also means that the FDA
might have to approve a smaller than normal trial, and sometimes perhaps even a
faster trial, she added.
“It’s an area where our technology is well-suited,” Bowyer
continued, referring to the antisense oligonucleotides that form the
backbone of all Ionis drugs. “We have been able to focus on several rare
diseases with a known target.”
By law, as outlined in the press release and in an e-mail from
Bowyer, the Orphan Drug Designation includes significant financial benefits for
Ionis: seven years of market exclusivity in the U.S. if the FDA approves the
drug, tax credits related to clinical trial expenses, FDA assistance in
clinical trial design, and a waiver of Prescription Drug User Fee Act filing
fees – over $1 million per drug as of fiscal year 2009.
“These benefits help manufacturers recover the costs of
developing a drug for small numbers of people,” Bowyer wrote. The Orphan Drug
Act was signed into law in 1983.
Kristina Bowyer (photo by Gene Veritas)
Trial ‘moving along well’
In IONIS-HTTRx, HTT stands for the gene huntingtin,
and Rx for medical treatment. The train has just recently begun, so, Ionis has
reported no official update at this time.
“Everything is moving along very well,” Bowyer said.
The new name
Ionis has also adapted well to its name change, announced on
December 18, 2015, in response to concerns about confusing the name Isis
Pharmaceuticals, Inc., with the acronym “ISIS” used in the English-language
media for the Middle Eastern terrorist organization, the Islamic State. Isis
Pharmaceuticals was founded in 1989.
“We want people when they hear or say our name to think about the
incredible drugs we’re developing and not a terrorist group,” Wade Walke,
Ph.D., vice president of communications and investor relations, told the press.
Ionis chose its new name based on employee suggestions.
“It seemed to me that everybody came together and decided
that Ionis was a nice-sounding, feeling name, as soon as someone hit on it,”
said Stanley Crooke, M.D., Ph.D., Ionis’s chairman of the board and CEO. The new moniker is a so-called empty vessel name and has no inherent meaning other than what the company does, he added.
Said Dr. Crooke:
“We’re here for the patients. We’re not here for our name.”
(Disclosure: I hold a symbolic amount of Ionis shares.)
The Ionis logo
Too late for Terry, other ‘HD angels’
I remember that Dr. Crooke spoke the same phrase – “We’re here
for the patients” – when I met him briefly during one of my first visits to the company
in the late 2000s.
I also remember visiting Terry Leach on Labor Day 2015. He was
slowly but inexorably slipping away from the ravages of juvenile HD, a particularly devastating form of the disease (click here to
read more about my visit).
Nevertheless, I was still shocked by his death on January 2.
What a horrible time to lose a family member. New Year’s will
forever remind Terry’s mother Angela and his siblings of his passing.
My immediate reaction that morning was one of intense anger.
No 18-year-old should die!
Having had the privilege of knowing Terry and his family, I felt
that I had failed as an advocate to speed the progress towards treatments.
Why hadn’t the Ionis trial come in time to save Terry and the
other “Huntington’s disease angels” who have passed in recent weeks?
I know that HD researchers may have similar thoughts, as they
work with the specter of this killer disease ever looming.
Terry Leach (family photo)
Keeping the faith
Later in the day, knowing that I needed to transcend my anger and
sadness, I recalled that a new year always brings hope. As I took a long,
strenuous walk with my dog through our hilly neighborhood, I renewed my resolve
to fight HD in 2016.
I spoke to Angela a few times that weekend. Instead of a wake and
church service, the family will hold a remembrance for Terry at the family home
on January 16. A Christian minister will preside.
At Angela’s request, I wrote some words for the back of the
remembrance cards she’s having made: “With his infectious smile and fortitude,
Terry set an example for all to follow. His life was short, but full of love
and joy. He is now free to walk with the Lord.”
Understandably, Angela was too drained to talk much. She did
confirm that Terry – despite his inability to talk, his confinement to a
wheelchair, and years of ingesting food through a feeding tube – had achieved
his high school diploma. He had attended school through mid-2015, receiving
assistance in a program for the disabled.
I asked Angela if she had any words for the HD community.
She said: “Just to keep their faith.”
Angela Leach in 2012 holding artist Lee Ellingson's drawing of her son Terry as "SuperTerry," the superhero who knocks out Huntington's disease (photo by Gene Veritas)
