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Expanding Treatment Options with Novel Therapies
Specialty Pharmacy Pipeline | Drugs to Watch
Anticipated Launches | Q4 2018-Q1 2019
Hemophilia A is a gene-related disease in which patients produce insufficient amounts of the blood clotting protein factor VIII.
Factor IX deficiency — or Hemophilia B — affects 1 in 25,000 to 30,000 men. Approximately one-half have mild to moderate disease (differentiated by having Factor IX activity above or below one percent of normal).
Treatment for hemophilia A consists of factor VIII replacement products (recombinant or plasma-derived) and, now, emicizumab (a monoclonal antibody that activates Factor X). Treatment for hemophilia B consists of factor IX replacement products (also plasma-derived or recombinant). Additional varieties of recombinant products that have been introduced in recent years help increase the half-life, or duration of effectiveness, through fusion with stabilizing proteins and other changes.
New Treatment Options
Since the 1990s, the standard of treatment for hemophilia A were drugs called bypassing agents (BPAs), which made it possible to treat patients who had become resistant to conventional drug regimens.
Emicizumab offers a novel mechanism of action for prophylaxis to reduce bleeding episodes, as well as a subcutaneous route of administration and less frequent dosing (than use of intravenously administered factor VIII products for prophylaxis). Both of these characteristics are generally preferred by hemophilia A patients. However, it is just one among several promising new drugs in the hemophilia pipeline that could help change the treatment paradigm for patients, including many young children.
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Challenges of Hemophilia Treatment
Hemophilia A is typically treated by administering intravenous doses of the missing blood factor. Factor VIII replacement is employed both for the acute treatment of active bleeds and prophylactically to prevent bleeds from occurring. An estimated 20 to 30 percent of the roughly 15,500 patients with hemophilia A in the U.S. develop significant levels of these inhibitors.
Use of factor VIII may lead the body to produce antibodies — or inhibitors — against the drug, causing treatment to become ineffective.
Inhibitors increase the risk of bleeds and complications, as well as mortality, by rendering the most common factor replacement ineffective. They can be treated through immune tolerance induction (ITI) therapy, but the process is lengthy — it can take two years or more — and demanding.
Historically, inhibitor patients also have had a higher risk of comorbid complications including joint damage, pain, and increased risk of death. They are twice as likely to be hospitalized and their treatment costs are historically five times higher than noninhibitor patients, often exceeding $1 million annually.
High Cost, High Efficacy
Emicizumab is a monoclonal antibody that mimics the function of factor VIII in the blood clotting cascade, while eluding factor VIII inhibitors.
Emicizumab is also very expensive: $482,000 for the first year and $448,000 per year after that. At least one recent pharmacoeconomic study found that over a lifetime, prophylaxis with emicizumab reduced total health care costs compared to BPAs, while reducing bleeding episodes by more than half.
Emicizumab's effectiveness raises the possibility of using it in a variety of roles — for example, as a way to delay or completely avoid ITI therapy, or as a replacement for BPA while the patient is undergoing ITI therapy.
Patients with hemophilia vary widely in their needs, and it is crucial to provide them with the support they need to use medications consistently and correctly.
Managing Cost, Care
Novel drugs with a high price and a short history of clinical use can be difficult for payors to manage. Given that, it is crucial to understand acceptable and unacceptable uses of the drug, not just today, but on an ongoing basis. Prior authorization (PA) needs to be well-informed and sophisticated, especially because standards of care can be expected to evolve as the drug becomes more widely used and better understood. Our hemophilia PA program is set up to ensure that plan members meet the prescribing criteria for the current on-label use including a prior history of high-inhibitor titer (confirmed by lab testing). Our approval criteria also takes into account member outcomes — whether members are achieving and maintaining a reduction in frequency of bleeding episodes.
Although emicizumab is generally well tolerated, there are some significant side effects and drug interactions — in clinical trials, some patients experienced thrombotic events when taking emicizumab in conjunction with APCC.
Hemophilia patients vary widely in their needs, and it is of paramount importance to provide them with the support they need to use medications consistently and correctly. CVS Specialty provides that support through a dedicated, highly experienced Hemophilia CareTeam, consisting of a clinical pharmacist, pharmacy service representative, pharmacy technician, clinical nurse coordinator and clinical nurse. This team provides consistent, high-touch care based on individual member needs. In addition, we also launched a Hemophilia Inhibitor Care Program, comprised of specialists from CVS Specialty, specifically to support hemophilia patients who have developed inhibitors and may be candidates for the new drug and other replacement factors.
Though the number of hemophilia patients is small, the pipeline of new drugs for the condition is relatively rich. Many represent incremental improvements on current approaches, but there are also several drugs which use more cutting-edge technology, in trials.
- Fitusiran, an RNA-interference drug that “silences” part of the action of the gene responsible for hemophilia, is now in Phase III trials. It is projected to be a once-monthly injection that both inhibits antithrombins (which prevent clotting) and promotes production of thrombin (which encourages it).
https://hemophilianewstoday.com/2018/01/12/hemophilia-clinical-program-fitusiran-among-2018-goals-alnylam-pharmaceuticals-announces/.It is intended for use not just in hemophilia A, but in hemophilia B (which is caused by too-low levels of factor IX).
- Several gene therapies are in early-stage development. Their goal is to restore factor VIII production to normal levels without need of further treatment by inserting a corrected, functioning copy of the gene into cells. There are currently questions over durability of this approach (how well it will work over the long run) — several years or more — and researchers fear that it might not be appropriate for patients. Nonetheless, many clinicians, patients, and industry analysts are hopeful about the drugs’ prospects.
While it is unlikely that hemophilia A will become a curable disease in the foreseeable future, it is clear that treatment will continue to evolve, perhaps rapidly, over the next few years.
Selected Hemophilia Treatments in Development
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