Published January 3, 2016 in Managed Healthcare Executive
Is an HIV Vaccine on the horizon? There’s good news in efforts to combat HIV/AIDs and hepatitis C (hep C, HCV). These viral diseases are now more vulnerable because of improved gene-based targeting and communications around exposure from surveillance programs. Some feel, however, that policymakers could do more to prioritize resources to fully eradicate the diseases.
Following hep C and HIV product use trends along with coverage policy from various perspectives is a good way to determine how the current situation could impact the future of these diseases. Here’s more on the exciting pipeline developments surrounding these diseases, and some of the policy hurdles that advocates are trying to address.
The push for policy changes
The U.S. Department of Health and Human Services (HHS) Office of HIV/AIDS and Infectious Disease Policy’s Viral Hepatitis Action Plan is meant to increase engagement of public health professionals at all levels. The Action Plan calls for enhanced hepatitis surveillance, targeted efforts to address hepatitis C health disparities, and expanded strategic partnerships among federal and non-federal stakeholders.
With reports of mounting “evidence” that many public and private health plans are deliberately rationing care for Americans with the hepatitis C virus (HCV), advocates on the front lines in fighting viral hepatitis and HIV/AIDS are urging lawmakers to overturn state Medicaid and managed care policies that discourage testing, require prior authorizations, and create significant hurdles for patients to receive new curative treatments.
At the 2015 National Summit on HCV and HIV Diagnosis, Prevention and Access to Care, held in Washington, D.C. in June, HCV and HIV specialists further called on policy makers to pass state laws mandating that insurance plans follow evidence-based medical guidelines when covering HCV testing and treatment. These guidelines—published jointly by the American Association for the Study of Liver Diseases (AASLD), the Infectious Diseases Society of America (IDSA), and the Department of Veterans Affairs—support treatment in all HCV-infected people except those with a life expectancy of less than one year because of non-liver medical conditions. Moreover, the advocates urged states to enact laws requiring Medicaid programs to offer first-line HIV medications and new HCV drugs on their formularies and to cap the copayments for these therapies.
Perhaps the most significant near-term opportunity, however, is the potential for payers to become more amenable to changing coverage policies. The reimbursement situation in Europe is better now than it was just a few months ago now that Harvoni is reimbursed in all five major European Union markets. Completion of pricing negotiations in France this summer opens up access to all patients with significant fibrosis as well as all patients with both HIV and hepatitis C infections. Additionally, Gilead is seeing a pattern of shorter average treatment durations in both the U.S. and Europe. This is good news, because the trend could help the biotech firm convince payers and purchasers to make the drugs more accessible to patients.
HCV pipeline developments
Interferon has been a component of all treatment for HCV treatment for more than 20 years. It has also been a major cause of limited treatment success as it results in numerous adverse events, requires injection, and has variable activity against different HCV genotypes and in patients with different genetic backgrounds.
Adding ribavirin to interferon improves response rates, but contributes additional adverse effects and increases pill burden for patients—a similar problem seen in early days of HIV treatment strategies. The first directly acting antivirals (DAAs) for HCV, the protease inhibitors telaprevir and boceprevir, can only be used with interferon and ribavirin and add considerable complexity and adverse effects.
The current HCV treatment landscape has been completely transformed by multiple new DAA combinations that were approved in the past 18 months or are likely to be approved in the next year. These include:
- Sofosbuvir, a nucleotide polymerase inhibitor;
- Ledipasvir, marketed in a fixed-dose combination with sofosbuvir (Harvoni, Gilead Sciences); and
- Daclatasvir (Bristol-Myers Squibb), a third NS5a inhibitor already approved in Europe and likely to receive FDA approval in the near future, according to Infectious Disease Advisor.
The National Institutes of Health estimates 180 million HCV infections worldwide. Approximately 4 million Americans have HCV infection, with an additional 3.5 million in Europe and 1.3 million in Japan, according to the Centers for Disease Control and Prevention. Most of these people are not aware of their infection as they often do not feel or look sick. The U.S., Europe, and Japan comprise the bulk of the HCV opportunity and revenue for pharmaceutical companies due to the high product cost.
There are 11 known genotypes for HCV. The U.S., Europe, and Japan have approximately 6 million GT1 and 2 million combined GT2/GT3 infected persons.
The 2014 sales for HCV drugs stood at $14 billion. Sales projections for HCV drugs are about $20 billion annually for the next six to seven years, according to Seeking Alpha.
From the initial focus on genotype 1b, a cure is now possible as a result of the success rates of Viekira Pak (99% to 100% range) bettering Harvoni (95% to 96% range) from the clinical data reports. However, side-effect profile remains a contentious issue because of the combination of products in the Viekira Pak.
The FDA is requiring AbbVie to add new warnings to its Viekira Pak after deaths and liver transplants have been reported in patients who already have liver damage caused by the disease. AbbVie argues that inappropriate use by patients has caused the problem.
For the few whose diseases don’t respond or have virulent forms, there are still some options. In early 2015, both darunavir and atazanavir were approved in separate co-formulations with cobicistat, an alternate booster (Prezcobix, Janssen Pharmaceuticals; Evotaz, Bristol-Myers Squibb). A long-acting injectable antiretroviral regimen would be a welcome treatment option in both situations. Rilpivirine (Janssen Pharmaceuticals), an approved oral nonnucleoside reverse transcriptase inhibitor (NNRTI) and cabotegravir (ViiV Healthcare), an investigational integrase strand transfer inhibitor (INSTI), are being developed in nanosuspension formulation for intramuscular injection. Fostemsavir (BMS 663068, Bristol-Myers Squibb) is the product of an HIV-attachment inhibitor with a novel mechanism of action. It binds to HIV envelope protein gp120 to prevent the conformational changes needed to expose the CD4 binding site.
Finally, the NNRTI class of antiretrovirals has been widely and successfully used in clinical practice, yet no currently approved NNRTI has ideal features. Efavirenz has frequent although usually transient neuropsychiatric adverse effects. Rilpivirine is somewhat less potent. Etravirine is active in many efavirenz-experienced patients but its role in initial therapy has not been adequately defined. All NNRTIs have a low genetic barrier to resistance.
As a consequence, the guidelines no longer include NNRTIs among the recommended regimens. Doravirine (MK-1439, Merck) is an investigational NNRTI that appears to have many favorable features. It is dosed once daily and in vitro develops resistance by a unique pathway that does not overlap those of current NNRTIs, according to Infectious Disease Advisor.
Genotype 2 and genotype 3 is new focus
Sovaldi is the only option for patients at this time. Merck’s MK-5172 (Grazoprevir)/MK-8742 (Elbasvir) is a once-daily single-tablet regimen for HCV with a 12-week course. On April 8, 2015, this drug received FDA’s breakthrough therapy designation, though it was not available as a marketed product at press time.
Here are some other noteworthy developments:
- Achillion has several trials going on and can be a future contender in the HCV market.
- Johnson & Johnson’s Simeprevir (Olysio) is approved in combination with other drugs.
- Bristol-Myers Squibb’s Declatasvir is approved in combination with Gilead’s Sovaldi.
- Gilead is working on a pan-genotypic single-table regimen, which has the potential to treat HCV patients regardless of their genotype. There are two ongoing trials that are currently in phase 3 and phase 2.
- AbbVie has two ongoing trials, one for GT1 as interferon-free combination and another as next-generation HCV combination.
- Paritaprevir (ABT-450), one of the constituents of the Viekira Pak, was developed as collaboration between AbbVie and Enanta Pharmaceuticals. They currently have two other candidates ABT-439 and EDP-239 in phase 2 and phase 1 trials respectively.
- Regulus Therapeutics‘ lead candidate is RG-101, which is administered as a subcutaneous dose in combination with J&J’s simeprevir (Olysio).
There is excitement surrounding potential new, highly effective treatments for HCV. However, the search for a vaccine isn’t anywhere near achieving such success. The first and only study to test a hepatitis C vaccine among at-risk humans began in March 2012. Results are expected after it’s scheduled completion in January 2016. The NIH–sponsored phase 1/2 study includes 450 injection-drug users, who receive counseling and referral to drug treatment programs. All other hep C vaccine research is in earlier stages.
The success of oral therapy treatments, such as Harvoni, has led many to believe that a vaccine is no longer necessary, although some healthcare industry executives disagree. It is not a surprise that Gilead Sciences has gained FDA approval for the expanded use of Harvoni, however, it becomes a question of getting the drug through the FDA bureaucracy.
HIV/AIDS pipeline developments
Recently approved drugs have expanded options for treatment and agents in the development pipeline may further advance HIV treatment and prevention, according to Infectiuos Disease Advisor.
- Dolutegravir, an INSTI, is a recent addition to the antiretroviral armamentarium.
- Truvada (tenofovir/emtricitabine) is used by about 29% of all treated HIV patients in the U.S., including 14% of the treatment-patient share. Truvada is the first drug approved by FDA that can be used to prevent HIV in high-risk individuals.
- Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) is the second most prescribed HIV regimen across all patients in the U.S. and has managed to capture 28% of the treatment-naïve patient share (HIV-positive patients who have never taken any antiretroviral therapy) for their infection.
- Complera (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) is the third most-prescribed HIV regimen across all patients and accounts for 20% of the treatment-naïve population.
- Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate) is the most prescribed HIV regimen in the country, as it is prescribed to about 22% of all patients treated.
Gilead Sciences is currently facing competition from companies such as GlaxoSmithKline and Pfizer, which through their joint venture, ViiV Healthcare, have created a substitute for Atripla called Tivicay (dolutegravir). Roche and Bristol-Myers Squibb are other major companies competing with Gilead Sciences in the HIV space.
With treatment well in-hand and select improvements still in-demand, the focus has turned back more to prevention as millennials are entering the high-risk groups for spread of HIV. Other risk factors have been managed, such as blood supply and casual sex, but diligence around prevention remains an important issue as new generations of sexually active adults enter high school, college, and the workforce.
Despite promising developments in the pipeline, it looks increasingly less likely that a vaccine will be fully developed in HCV and only incremental progress for an HIV/AIDS vaccine will occur.
Owing to the current successes in HIV/AIDS and HCV therapy options, manufacturers have little incentive to make significant investments in basic or applied research for these diseases compared to other disease states. And, because of financial burdens required of providers and plans under the ACA, financial resources are limited for other use in academic medical centers, too.
That leaves population efforts through health plans to address the cause of exposure to these diseases rather than treatment. It remains to be seen how well supported preventative options and patient care delivery will be around HCV or HIV/AIDS in the U.S. through the end of this decade.
F. Randy Vogenberg, PhD, partner, Access Market Intelligence, and cofounder National Institute of Collaborative Healthcare, Greenville, S,C. John Santilli, MBA, is partner, Access Market Intelligence, and cofounder National Institute of Collaborative Healthcare, Trumbull, Connecticut.