Miracles, it seems, have a high price tag. At least, if those miracles are miracle drugs. There’s no doubt that trends in gene therapy and immuno-oncology are producing drugs that are as close to miraculous as we’re likely to get, doing a great job, generally, in beating back diseases that to this point were untreatable or didn’t respond well to other therapies.
Miracles, it seems, have a high price tag. At least, if those miracles are miracle drugs. There’s no doubt that trends in gene therapy and immuno-oncology are producing drugs that are as close to miraculous as we’re likely to get, doing a great job, generally, in beating back diseases that to this point were untreatable or didn’t respond well to other therapies.
It’s also true that many of these drugs have astoundingly high price tags. The most expensive drug in the U.S. is Horizon Pharma ’s Actimmune for a rare disease, chronic granulomatous, which runs about $52,321 for a single month’s treatment, for example. Sarepta Therapeutics’ Exondys 51 for Duchenne muscular dystrophy has a yearly price tag of about $300,000.
One disease that is getting some attention lately for its costs is hemophilia. It is a rare bleeding disorder. A gene mutation prevents blood from clotting properly. It is generally passed from mother to son.
But according to a 2015 Express Scripts report, the drugs to treat hemophilia cost more than $270,000 annually on average. And that’s for patients who don’t have complications from their disease, where the annual price can climb above $1 million.
In the U.S., there are about 20,000 patients, but AllianceBernstein, an investment research firm, estimates the hemophilia market in the U.S. is worth about $4.6 billion.
There are currently 28 different hemophilia drugs available in the U.S., with another 21 in development. They are typically biologics, with no current biosimilars available. Biologics are notoriously expensive. One of the peculiarities of the hemophilia market is that with so much competition, the prices haven’t come down. Jerry Avorn, a professor at Harvard Medical School, told NPR, that this hasn’t brought prices down in the way someone “operating at the level of undergrad Econ 101 would expect.”
NPR points out, “The problem is that companies have no incentive to lower prices. Patients generally don’t push back because insurers pay the bulk of the cost. And insurers tend not to object because the market for the drugs—expensive as they are—is small and the patients are especially vulnerable.”
Acorn noted to NPR, “It’s a magical formula: Lifesaving drug, child at risk of bleeding to death—it kind of casts anybody who looks at costs into the role of some evil Scrooge-like person. The insurers don’t want to end up on the front page of the newspaper saying Little Timmy bled to death because his drug wasn’t covered.”
And, of course, no company wants to be the first one to cut prices in a potential drug war.
The first products to treat hemophilia came out in the mid-1960, were which derived from human blood plasma. But in the 1980s, when HIV emerged, these products, unfortunately, spread HIV into the blood supply, infecting about 4,000 hemophilia patients.
In the 1990s, cloning human clotting proteins in animal cells using recombinant DNA technology took over, which is difficult to make. Bayer, for example, has a factory in Berkeley, California that produced the drug Kogenate. When at full capacity, it produced less than a pound of clotting factor annually. But when diluted with other ingredients, it is used to treat thousands of patients in 80 countries.
But it’s still an area of interest for many companies, no doubt because of the profitability related to a lifetime chronic disease whose medications justify six-figure price tags, but also because the technology is advancing where therapies are improving. Here are a few examples.
On May 22, 2018, BioMarin Pharmaceutical announced an update to its previously reported Phase I/II trial of valoctocogene roxaparvovec, a gene therapy for severe hemophilia A. The company has six clinical studies ongoing in its comprehensive gene therapy treatment of severe hemophilia A. There are two Phase III trials, a Phase I/II trial, and two additional and separate studies, one to evaluate seroprevalence in people with severe hemophilia A and one non-interventional study to evaluate baseline characteristics in hemophilia A patients.
In the 6e13 vg/kg cohort, the trial to date showed continued and substantial decrease in bleeding requiring Factor VIII infusions with a 97 percent reduction in mean Annualized Bleed Rate (ABR), with no spontaneous bleeds and elimination of all bleeds in targets joints in the second year.
Also on May 22, Spark Therapeutics, along with Pfizer, released data from an ongoing Phase I/II clinical trial of SPK-9001 for severe or moderately severe hemophilia B. The companies reported that all 15 participants had discontinued routine infusions of factor IX concentrates, none of them experienced serious adverse events, and there were no thrombotic events or factor IX inhibitors.
“We are pleased to see all 15 participants, notably including the first four participants who have been followed for more than two years, continue to show that a single administration of SPK-9001 has resulted in dramatic reductions in bleeding and factor IX infusions, with no serious adverse events,” said Katherine High, Spark Therapeutics’ president and head of research & development in a statement at the time.
And on June 4, the U.S. Food and Drug Administration (FDA) accepted Genentech’s supplemental Biologics License Application (sBLA) and granted Priority Review for Hemlibra (emicizumab-kxwh) for adults and children with hemophilia A without factor VIII inhibitors. A decision will be made by October 4, 2018. The therapy was approved in November 2017 for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A with factor VIII inhibitors. It was also approved for the same population by the European Commission in February 2018.
Hemlibra is a bispecific factor IXa- and factor X-directed antibody designed to bring together factor IXa and factor X, proteins needed to activate the natural coagulation processes and restore the blood clotting process for hemophilia A patients.
