MedCart Specialty Pharmacy: Preparing for the Next Advancements in Hepatitis C Therapy

Therapy approvals significantly changed the landscape of treatment for hepatitis C and it is anticipated that the drugs in the treatment pipeline will mark significant advances in therapy as well.

There was much anticipation surrounding the new hepatitis C treatment options that were granted FDA approval in May 2011. Victrelis (boceprevir, Merck) and Incivek (telaprevir, Vertex) are both direct-acting protease inhibitors that were approved for the treatment of chronic hepatitis C genotype 1 infection in combination with peginterferon alfa and ribavirin in adult patients (18 years or older) with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon or ribavirin therapy.^1,2

Just as those therapy approvals significantly changed the landscape of treatment, it is anticipated that the drugs in the hepatitis C treatment pipeline will mark significant advances in therapy as well. Hepatitis C virus (HCV) is a leading cause of chronic liver disease. It is estimated that 180 million people are infected worldwide. In the United States, the prevalence of HCV infection is estimated to be 1.6%, or approximately 4.1 million people. Hepatitis C is the primary cause of death from liver disease and the leading cause of liver transplantation in the United States. The American Association for the Study of Liver Diseases (AASLD) suggests that mortality related to HCV infections will rise over the next 2 decades.³

Current Treatment of HCV Genotype 1 Infection

The goal of HCV therapy is to prevent complications and death from HCV infections. This is achieved through a sustained virologic response (SVR), which refers to no detectable HCV RNA being found in the blood 24 weeks after stopping treatment. SVR is associated with long-term clearance of HCV infection and improved morbidity and mortality.⁴

The AASLD released an updated practice guideline in 2011 to address the addition of boceprevir and telaprevir to the HCV genotype 1 armamentarium. According to the 2011 AASLD guidelines, the optimal therapy for genotype 1 chronic HCV infection is the use of boceprevir or telaprevir in combination with peg-interferon alfa (either Pegasys or Peg-Intron) and ribavirin.⁴ Now that boceprevir and telaprevir have been on the market for almost 19 months, there has been wide adoption of the 2011 guideline update in clinical practice, leading to significant clinical experience for those pharmacies that treat patients with hepatitis C. One such pharmacy with experience in treating hepatitis C patients is MedCart Specialty Pharmacy.

MedCart Specialty Pharmacy Hepatitis C Program

MedCart Specialty Pharmacy applies the knowledge, experience, and skills of its clinical staff to help optimize drug therapy outcomes for its HCV patients. At their state-of-the-art facility in Livonia, Michigan, MedCart Specialty employees help patients in the fight against hepatitis C by placing emphasis on the patient’s ability to access medication and maintain a high quality of life during pharmacotherapy. MedCart Specialty has developed a patient-centric model of care that addresses the coordination of benefits as well as the maintenance of an open and reliable channel of communication among all stakeholders. In addition, MedCart Specialty has created a taskforce within its patient care department that is dedicated to the mitigation of drug side effects that are often experienced by patients embarking on hepatitis C therapy.

Because out-of-pocket costs for HCV therapy can create considerable barriers to accessing treatment, MedCart Specialty Pharmacy’s Patient Financial Resources Department employs funding specialists to help reduce the risk of nonadherence due to financial considerations. The funding specialists coordinate with third party payers, drug manufacturers, community-based social work organizations, nonprofit groups, and disease foundations to help devise individualized yet comprehensive strategies to minimize the financial burden of HCV therapy to the patient.

Another important way that MedCart Specialty Pharmacy promotes a high level of medication adherence and persistency is through proactive clinical intervention by the pharmacy care staff for the duration of HCV treatment. This is accomplished throughout the treatment regimen and begins with motivational interviewing prior to a patient starting on therapy. Patients receive one-on-one educational training on the disease, the treatment regimen, expectations from treatment, and what to anticipate during the therapeutic journey. Another key component to the MedCart Specialty HCV program is empowering the patient to know to whom they can reach out for direction, clinical support, and questions that may arise.

Continued outreach during HCV treatment allows for the creation of a therapeutic relationship between the pharmacy staff and the patient—and it also allows for various data sets to be obtained throughout treatment. This enables further analysis of the patient’s treatment experience and provides alerts to pharmacy staff of those patients who may need escalated levels of intervention by MedCart’s clinical staff to optimize therapy outcomes.

MedCart Specialty clinical and patient care staff utilize a variety of resources to carry out this creative approach to outcome-based care. Patient care may be supplemented by the use of adherence tools such as TextMed, a custom text messaging medication reminder service; MedPac compliance packaging; or by communicating with the physician regarding any complementary and adjunct therapies that may help mitigate therapy side effects. Furthermore, these patients also may be referred to support groups to deal with the emotional toll of this disease and to connect with other patients who are going through similar experiences.

To provide outstanding care to patients and providers and to recognize additional savings and services that positively impact the bottom line, MedCart Specialty works with collaborative partners such as Managed Health Care Associates, Inc (MHA), a leading health care services company. MHA’s Specialty Pharmacy Solutions program supports MedCart Specialty with clinical information to enhance disease state and specialty product knowledge as well as contract analytics and reporting to facilitate understanding of therapy- specific and population metrics. MHA’s Specialty Pharmacy Solutions also provides consistent tracking and analysis of trends in specialty pharmaceuticals to help MedCart Specialty anticipate what might be on the horizon and how to be in the best position to grow business and expand opportunities in the marketplace. MHA Specialty Pharmacy Solutions clinical services help MedCart Specialty keep apprised of the pipeline so that its hepatitis C clinical practice and expertise can evolve along with new therapy developments.

Hepatitis C Treatment Pipeline⁵

Just as the addition of boceprevir and telaprevir altered the HCV treatment paradigm, the current pipeline agents are anticipated to shift the HCV treatment landscape once again. Many agents are being developed with the goal of eliminating concomitant therapy with interferon in an effort to reduce the overall side effect burden of hepatitis C therapy (Table 1).

It is anticipated that most of the new agents will initially come to market approved for combination therapy with pegylated interferon and ribavirin, and then gain approval in interferon-free regimens. Additional agents are looking at finding better regimens for treating HIV/HCV coinfected patients. There is some notion in the marketplace that physicians are again opting to defer treatment until newer regimens become available, much like what was seen prior to the approvals of telaprevir and boceprevir.^6,7 Several hepatitis C investigational agents are highlighted below.

Boehringer Ingelheim’s faldaprevir is being evaluated as a once-daily oral NS3/4A protease inhibitor in combination with pegylated interferon and ribavirin, as well as in an interferon-sparing regimen both with and without ribavirin in combination with another investigational agent, BI-207127 (an NS5B RNA-dependent polymerase inhibitor).⁸ Boehringer Ingelheim’s hepatitis C virus clinical development program is referred to as HCVerso^TM.

Daclatasvir, from Bristol-Myers Squibb, is a once-daily NS5A replication complex inhibitor being studied for use up to 24 weeks in combination with pegylated interferon and ribavirin. It is also being studied with the investigational agent asunaprevir (BMS-650032, a twice-daily NS3 protease inhibitor) in a quadruple regimen consisting of daclatasvir, asunaprevir, pegylated interferon, and ribravirin, and in an all-oral regimen consisting of asunaprevir plus daclatasvir.

Janssen’s simeprevir is a once-daily oral NS3/4A protease inhibitor being studied in phase III trials in combination with pegylated interferon and ribavirin. It is also being studied with other direct-acting antiviral agents as part of interferon-free regimens, both with and without ribavirin.⁹

Sofosbuvir is Giliead’s once-daily oral NS5B polymerase inhibitor. It is being studied in phase III to treat HCV genotype 2 or 3 in combination with ribavirin for 12 weeks and is also being studied in Phase III in a combination including ribavirin plus a fixed-dose combination of sofosbuvir plus GS-5885 (an NS5A inhibitor) for 12 or 24 weeks to treat genotype 1 HCV.

Abbott’s hepatitis C treatment pipeline consists of ABT-450, a protease inhibitor that requires boosting with ritonavir; ABT- 267, an NS5A inhibitor; and ABT-333, a nonnucleoside polymerase inhibitor. These experimental agents have been studied with and without ribavirin for either 12 or 24 weeks in all-oral treatment regimens. Abbott announced that phase III clinical trials for these agents would begin in October 2012.

Vertex has VX-135 (a nucleotide analogue inhibitor of hepatitis C polymerase) and VX-222 (an oral nonnucleoside inhibitor of hepatitis C polymerase) currently in phase II development and is exploring opportunities to partner with other manufacturers to create an efficacious regimen.^7,10

Bristol-Myers Squibb is also developing pegylated interferon lambda for hepatitis C treatment. The human interferon lambda proteins are generated by the immune system in response to viral infection and signal through a different receptor than interferon alpha. This particular receptor is found on fewer cells throughout the human body than the receptor for interferon alpha; therefore it is thought that interferon lambda may be able to offer an improved safety and tolerability profile.¹¹

Valeant sought to develop taribavirin (KD024, viramidine), which is a prodrug of ribavirin. The goal of this drug is to preferentially target the liver while significantly reducing the anemia associated with ribavirin.¹² Phase III trials from 2006 did not meet the noninferiority efficacy end point on an intentto-treat basis, but did confirm the safety advantages of taribavirin. Valeant has since entered into a strategic agreement with Kadmon to pursue additional clinical trials with higher or weight-based dosing.^13,14

Alisporivir (DEB025) is Novartis’ cyclophilin blocker that showed promising efficacy, but development was placed on hold when a small number of patients developed pancreatitis in trials. Additional analysis is being conducted to determine if the increased risk of pancreatitis was caused by alisporivir.¹⁵

The above information is a selective summary of publicly available information and is accurate as of the date of writing. Please consult the sources for complete reference information. The views expressed in this article are those of the author alone and not of Managed Health Care Associates, Inc, or MedCart Specialty Pharmacy. Any patient care, treatment, dosing or other decisions related to the subject matter of this article should be based on an independent evaluation of the patient’s condition and medical history by his/her treating physician.

About the Author

Ed Saleh, RPh, is the cofounder and chief executive officer of MedCart Specialty Pharmacy. An alumnus of the Wayne State University School of Pharmacy in Detroit, Michigan, Mr. Saleh began his career at Sigmapharm Co, a community-based independent pharmacy group serving the needs of both the Hispanic and indigent populations of Detroit, where he held the position of president. He has also worked alongside many regional and national non-profit organizations to help increase access to health care resources for Michigan’s senior citizen community. Mr. Saleh has held leading positions within Goldberg Int and Worldpharm Inc, in the latter of which he still serves as chairman of the board. The extensive community outreach and dedication to the fight against chronic diseases by Mr. Saleh has afforded MedCart Specialty Pharmacy national peer recognition.Stacey Ness, PharmD, RPh, MSCS, has worked in both national specialty pharmacy and payer organizations and has experience in clinical management, adherence, and persistency programs, as well as chronic disease cost optimization strategies. Dr. Ness is active in the Consortium of Multiple Sclerosis Centers, Academy of Managed Care Pharmacy, National Home Infusion Association, and Hematology and Oncology Pharmacy Association, and has served on the Minnesota Medicaid Drug Formulary Committee since 2008. She is a multiple sclerosis certified specialist and currently serves as the director of specialty clinical services at Managed Health Care Associates, Inc, a health care services organization based in Florham Park, New Jersey.

References

• Incivek prescribing information. Vertex October 2012. http://pi.vrtx.com/files/uspi_telaprevir.pdf. Accessed October 27, 2012.
• Victrelis prescribing information. Schering Corporation, a subsidiary of Merck and Co. July 2012. www.merck.com/product/usa/pi_circulars/v/victrelis/victrelis_pi.pdf. Accessed October 27, 2012.
• AASLD practice guidelines: diagnosis, management, and treatment of hepatitis C: an update. Hepatology. April 2009. www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/Diagnosis_of_HEP_C_Update.Aug%20_09pdf.pdf. Accessed October 27, 2012.
• An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. www.aasld.org/practiceguidelines/Documents/2011UpdateGenotype1HCVbyAASLD24641.pdf. Published October 2011. Accessed October 23, 2012.
• Clinical Trials Registry. United States National Institutes of Health, 2012. www.clinicaltrials.gov. Accessed October 27, 2012.
• Gilead Sciences’ hepatitis C drug candidate may have first mover advantage. iStock Analyst, August 2012. www.istockanalyst.com/finance/story/5983419/gilead-sciences-hepatitis-c-drug-candidate-may-have-first-mover-advantage. Accessed October 27, 2012.
• Wanted: premier hepatitis C drug developer to partner with Vertex. Fierce Biotech, October 19, 2012. www.fiercebiotech.com/story/wanted-premier-hepatitis-c-drug-developer-partner-vertex/2012-10-19. Accessed October 27, 2012.
• Hepatitis C: interferon-free combination of BI 201335 plus BI 207127 and ribavirin shows up to 76% of patients achieve a virological response at week 12, and 59% achieve SVR12 with 16 weeks treatment. Boehringer Ingelheim, November 2011. www.boehringer-ingelheim.com/news/news_releases/press_releases/2011/07_november_2011hepc.html. Accessed October 27, 2012.
• Simeprevir (TMC435) data in hepatitis C to be presented at the annual meeting of the American Association for the Study of Liver Diseases. PRN Newswire, October 16, 2012. www.prnewswire.com/news-releases/simeprevir-tmc435-data-in-hepatitis-c-to-be-presented-at-the-annual-meeting-of-the-american-association-for-the-study-of-liver-diseases-174342921.html. Accessed October 27, 2012.
• Vertex research and development pipeline. Vertex 2012. www.vrtx.com/research-development/pipeline. Accessed October 27, 2012.
• Pipeline asset update for PEG-Interferon Lambda. Bristol-Myers Squibb 2012. www.bms.com/research/investigational/hepatitis/Pages/PEG_interferon_lambda.aspx. Accessed October 27, 2012.
• Clinical pipeline. Kadmon 2012. http://kadmon.com/docs/science_pipeline. Accessed October 27, 2012.
• Valeant Pharmaceuticals reports VISER2 results for Viramidine(R); company initiates phase 2b weight-based dose-ranging study. Business Wire, 2006. www.natap.org/2006/HCV/091506_04.htm. Accessed October 29, 2012.
• Viramidine fails to show non-inferiority to ribavirin at tested doses, but causes less anemia. www.hivandhepatitis.com/hep_c/news/2010/011910_a.html. Accessed October 29, 2012.
• Hepatitis C drug alisporivir is effective, but pancreatitis a concern. Aidsmap, April 2012. www.aidsmap.com/Hepatitis-C-drug-alisporivir-is-effective-but-pancreatitis-a-concern/page/2326524/. Accessed October 29, 2012.