Ben Fidler August 10th, 2018
[Updated at 4:08 pm ET, see below]
Alnylam Pharmaceuticals made history this afternoon.
The FDA has just approved Alnylam’s patisiran (Onpattro), making it the first
medicine specifically cleared to treat a rare and deadly disease called
hereditary transthyretin amyloidosis (hATTR). The decision is a scientific
milestone too: it marks the first-ever approval for a medicine that uses RNA
interference (RNAi), a method cells can use to silence a gene before it makes a
harmful protein.
[Updated here and below with details on
pricing, patient population size, and the value-based pricing scheme.] The
FDA’s approval is specifically for the treatment of the peripheral nerve damage suffered by hATTR patients. On a
conference call Friday afternoon, Alnylam said it will discuss with the FDA how
to expand the drug’s label to include other hATTR patients with other kinds of
symptoms, such as heart problems, which might require additional study. Company
officials estimated there are 20,000 to 30,000 patients worldwide with hATTR
and the nerve damage, including fewer than 3,000 adults diagnosed in the US.
Alnylam also said the drug’s average list
price–which doesn’t include rebates to insurers—is $450,000 per patient, per
year. The average net price, taking rebates into account, is $345,000 per year,
Alnylam said.
Alnylam executives have been vocal for years about
plans to tie their drug’s price to the benefit it provides patients. And today
the company made good on that promise, though it didn’t disclose specifics. In
a statement on Friday, Alnylam said it has agreed in
principle to the structure and key terms of “value-based agreements” with
“major health insurers” including Harvard Pilgrim Health Care. Through these
deals, Alnylam would be paid based on patisiran’s ability “to deliver outcomes
in the real world setting comparable to those demonstrated in clinical trials,”
the company said.
In the conference call, Alnylam leaders said
that under these agreements, treated patients would be evaluated annually by
their doctors using clinical measures. If the patient improves and nerve damage
is reversed, Alnylam said it would be paid in full. But if the disease gets
worse, the company would provide discounts of varying levels, but officials
didn’t give any further detail on the discounts.
Alnylam’s (NASDAQ: ALNY)
triumph, however, doesn’t guarantee a big revenue surge from sales of the
company’s first product. There may be many patients who remain undiagnosed or
misdiagnosed, and a competing company’s similar drug could be approved in the
U.S. soon.
Nonetheless, patisiran’s approval is a
noteworthy scientific achievement. It is the culmination of nearly two
decades of scientific work that began when scientists Andrew Fire and Craig
Mello discovered RNAi 20 years ago. They won a Nobel Prize for
their discovery in 2006.
Since 2002, Alnylam, the RNAi field’s biggest
company, has tried to use the method to make drugs, undergoing a series of ups and
downs, clinical setbacks, and more before getting patisiran to the finish line.
It took years to figure out how to deliver
large RNA molecules safely and effectively into cells, and pharmaceutical
companies fell in and out of love with RNAi along the way. But Alnylam has
survived, in large part, because of early partnerships that left it with enough
cash to weather the storm.
After burning through almost $2.4 billion, SEC
filings show, the company is now a commercial business with a product soon to
be on the market. Three other Alnylam RNAi medicines for hemophilia, high
cholesterol, and acute hepatic porphyria (a rare liver disease) are in
late-stage testing.
“After 16 years, tireless perseverance through
near-death moments, billions of dollars in investment, we’ve finally succeeded
in advancing RNAi therapeutics as a whole new class of innovative medicines,”
said CEO John Maraganore (pictured) in an e-mail to Xconomy. “What matters
most? The difference we can now make in the lives of patients with hATTR
amyloidosis.”
hATTR is estimated to affect 50,000 people
worldwide. People who have the disease make a mutated version of the protein transthyretin
(TTR), which builds up in misfolded clumps, causing damage to a variety of
tissues around the body. Some patients suffer just the nerve damage, which
starts with numbness in the toes, then feet, and moves upwards. Others suffer a
corrosion of the heart’s wiring that can lead to heart failure and death. Most
patients have elements of both issues.
The only treatments to date in the U.S. are
liver transplants or diflunisal, a generic anti-inflammatory drug used
off-label to “stabilize” the TTR protein and slow the progressive nerve damage.
But liver transplants are risky, tough to get, and don’t always work. And
diflunisal can cause stomach or kidney problems, so it isn’t for everyone.
The treatment paradigm for hATTR is now being
upended, however. Alnylam’s drug is a small RNA molecule, delivered to the
liver by a lipid nanoparticle, that works by interfering with the RNA for
the abnormal form of the protein transthyretin (TTR) to block the
production of the protein.
With the arrival of patisiran and a rival,
similar-type drug, inotersen (Tegsedi), from Akcea Therapeutics (NASDAQ: AKCA),
new drugs are emerging that could give patients the chance to halt the
progression of their nerve damage—and in some cases, improve nerve function.
European regulators approved
inotersen in July and the FDA could approve it by Oct. 6.
Patisiran is currently under review in Europe.
Then there’s tafamidis (Vyndaqel), a Pfizer
drug which is similar to diflunisal and is approved in Europe but not in the
U.S. Pfizer (NYSE: PFE) could soon file for approval for hATTR patients with
heart problems, and detailed results from a Phase 3 study are expected later
this month. Those results, and whether the FDA ultimately approves tafamidis—it
rejected the drug several years ago—could affect the commercial potential of
both patisiran and inotersen.
Last week, Xconomy delved into the
impact patisiran’s approval could have on patients, clinicians, and payers, and
the questions and challenges ahead. It’s unclear how long
patisiran and inotersen’s benefits will hold up, who will respond, or whether
any safety problems will crop up over time. There is also little information
about the impact the drugs have on cardiac symptoms—like thickening of the
heart tissue—that can kill patients more quickly. All of which could play into
how insurers cover the drugs, how physicians prescribe them, and who might be
able to access them.
Clinical trials have different designs and
circumstances, so comparing one drug to the other is fraught with caveats. But
the biggest differences between the two drugs is how they are administered, and
their side effects. Alnylam’s drug is given via infusion at a clinic once every
three weeks and patients are given precautionary analgesics and corticosteroids
before each dose. Inotersen is a once-weekly self-administered subcutaneous
injection. Alnylam has touted patisiran’s safety profile (the most common side
effects are upper respiratory infection, and those related to the infusion,
including back pain, nausea and abdominal pain). However, worrisome kidney problems
and dangerously low platelet counts have cropped up in
clinical studies of inotersen—meaning patients will likely require frequent
monitoring.
Here’s more on Alnylam, RNAi,
and the coming
commercial battle between patisiran and inotersen.
Corie Lok contributed
to this report.
No comments:
Post a Comment