Isis Pharmaceuticals, Inc., based in Carlsbad, CA, has launched its long-awaited clinical
trial to test a drug designed to attack Huntington’s disease at its genetic
roots.
In a July 21 press release, Isis said it had initiated a Phase I human clinical study of ISIS-HTTRx,
its compound aimed at diminishing the symptoms of HD. HTTRx
signifies a medication for HD. The disease is caused by a defect in both the
huntingtin gene and protein, which are symbolized by the letters htt.
“ISIS-
HTTRX
is the first therapy to enter clinical development that is designed to
directly target the cause of the disease by reducing the production of the
protein responsible for HD,” the release stated.
In
partnership with Roche, the Switzerland-based pharmaceutical giant sharing
costs of the typically expensive clinical trial, Isis thus becomes the first
entity to use a gene-silencing technique in the attempt to stop HD.
“Although
the toxic protein produced from the huntingtin (HTT) gene in HD patients has
been a target of interest for many years, no therapies have advanced to
clinical trials to treat the underlying cause of the disease,” Frank Bennett,
Ph.D., Isis’s senior vice president of research, stated . “Our antisense
technology has enabled us to discover and develop ISIS-HTTRx, the
first therapeutic approach designed to treat the genetic cause of HD."
Frank Bennett, Ph.D., of Isis Pharmaceuticals (photo by Dr. Ed Wild)
A ‘significant milestone’
HTTRx is an antisense oligonucleotide, an
artificial strand of DNA created by Isis to block the action of the RNA
molecules that translate the huntingtin genetic code to make the huntingtin
protein.
Involving
about 36 early-stage HD patients at about six sites in Europe and Canada, the
Phase I trial focuses on the safety and tolerability of HTTRx.
According to an Isis spokesperson, the sites will start recruiting participants
as early as in a few weeks.
Depending
on the pace of recruitment, Phase I most likely will end in 2017. If Phase I is
successful, a larger Phase II trial to test efficacy likely would take place in
2018. A successful Phase II trial would be followed by a Phase III trial. Together
all three phases of a clinical trial program typically take at least five
years.
Last
August, scientists from Isis and CHDI Foundation, Inc., the nonprofit
virtual biotech firm that funded the early stages of the Isis research starting
in 2007, provided extensive details about the plans for the trial. (Click here
to read more.).
“The
initial development of this antisense drug for Huntington’s disease came out of
a longstanding productive partnership between Isis and CHDI, and its
advancement now to clinical trial is testament to Isis’ perseverance and
scientific expertise,” CHDI president Robi Blumenstein stated in the press
release. “It’s exciting that therapeutic candidates grounded in the biology of
Huntington’s disease are finally making their way to clinical trial.”
“The
initiation of the ISIS-HTTRx study is a significant milestone in the history of
Huntington's disease research as this marks the first time a drug designed
specifically for Huntington's patients has transitioned into the clinic,”
George Yohrling, Ph.D., senior director for mission and scientific affairs for
the Huntington’s Disease Society of America (HDSA), wrote in an e-mail. “My
hope is that this study not only shows that the drug is safe, but serves as an
informative beacon for all future huntingtin-lowering trials.”
Martha
Nance, M.D., the director of the HDSA Center of Excellence at Hennepin County
Medical Center in Minneapolis and a member of the executive committee of the
Huntington Study Group, said that “it would be impossible to overstate
the importance of this trial.”
“I
am old enough to have grown up in the 1960s, swept up as a young child with the
excitement of space exploration, and I remember, almost as clearly and
importantly as the Apollo 11 mission that actually LANDED on the moon, the
Apollo 8 mission over Christmas 1968, during which William Anders took the
iconic picture of the earthrise over the moon,” Dr. Nance wrote in an e-mail. “There
were several more steps, several more Apollo missions, before Neil Armstrong
could jump off the ladder onto the moon. The ISIS study is the HD equivalent of
the Apollo 8 mission.”
LaVonne Goodman, M.D., the founder of Huntington's Disease Drug Works, said that there are "high hopes and expectations" about the trial. "We celebrate those individuals with HD, heroes who are selflessly participating in this trial and all others, 'taking one for the team,'" she wrote in an e-mail.
“We’re
very enthusiastic about the drug,” Dr. Bennett said in a 2014 interview.
As
he put it previously, Isis technology is like a “laser-guided missile” that
targets a specific, disease-causing messenger RNA and destroys it or takes it
out of the body “so that you don’t produce that messenger RNA.”
The Isis-Roche partnership
According
to the press release, with the initiation of the clinical trial, Isis – a small
company – earned a $22 million milestone payment from Roche. To date, Isis has
earned $52 million in upfront and milestone payments from the partnership. It
can earn more as the project progresses, as well as royalties on potential
sales.
Roche
can exercise the option to license ISIS- HTTRx from Isis through the
completion of the Phase 1 trial. If so, Roche will assume responsibility for
global development, the acquisition of regulatory approvals, and marketing the
drug.
The
partnership is critical. Isis cannot alone afford to carry out a clinical
trial. Drugs usually cost hundreds of millions of dollars to develop.
According
to the press release, Isis’s drug projects include 38 drugs aimed at treating a
wide range of diseases, among them cardiovascular disease, metabolic disorders,
cancer, and severe and rare diseases, including neurological disorders such as
HD.
A huge dose of hope
The
announcement of the historic trial’s launch provides a huge dose of hope for
the HD community.
Since
the discovery of the huntingtin gene in 1993, scientists have published
thousands of research papers on HD and identified hundreds of potential
“targets” for treatments.
In
recent years, scientists and drug companies have initiated an increasing number
of clinical trials in the quest for effective treatments. However, to date none
has proven successful in halting the disease.
A necessary leap
As
seen in animal studies, the infusion of HTTRx into the brain has led
to the disappearance of the HD-like symptoms.
Scientists
warn that it’s a still a huge leap from animals to humans when it comes to
testing drugs. Also, only about one in ten clinical trials results in a drug
reaching the market.
Earlier
this year prominent HD specialist Bernhard Landwehrmeyer, M.D., Ph.D., cautioned that it could still take
decades for the gene-silencing approach to play an effective part in managing
the disease.
“We
should all be extremely excited and hopeful, but remember that there is a lot
of work ahead for researchers, doctors, patients, and families before we will get
to our moon, and no guarantee of success,” wrote Dr. Nance.
Nevertheless,
the Isis-Roche trial is a major step. At a minimum, it will help answer key
questions about the gene-silencing approach.
If
it is successful in ameliorating symptoms, it could mean the beginning of the
end of Huntington’s disease as a threat to the tens of thousands of families
affected worldwide.
* * *
Below
see links to previous reports on Isis.
Also see coverage at HDBuzz by clicking here.
(Disclaimer: I hold a symbolic number of Isis shares.)
5 comments:
Awesome!
Is it expensive treatment? I mean ISIS-HTTRx itself and delivering into the spinal? I consider such type of cerement will be refunded by the government.
Have you heard anything about using Vitamin B3 (Niacin) for Huntington's Disease?
I came across an old article by the late Dr. Abram Hoffer (he was a biochemist & psychiatrist I believe) from the 1970s mentioning someone with HD who came to him. The patient took Niacin and his neuro symptoms disappeared, something like that??
I haven't seen anything else on that so I'm checking out various blog posts etc
I am happy for this progress but sad to have to read about the royalties to the compamny. In the end it makes it clear this is still about corporate business, will HD families be able to afford it?
Why is it sad for them to earn royalties on the treatment? The hard-working scientists that are developing this drug deserve to be paid for their dedication. This is their job, they have families to feed, mortgages and student loans to pay.
Sure, the drug will probably be expensive -- in large part because the *trials* are so expensive to conduct, not simply because people are greedy -- but that's why we have health insurance. No individual or family can reasonably be expected to pay for this kind of treatment from out-of-pocket, and no treatment like this could realistically be developed inexpensively enough for people to do so. That's why medical insurance (or nationalized health care) exists.
Post a Comment