FDA Move Aims to Diversify HCV Test Maker Market, Reduce Regulatory Burden
On November 19th, the Food and Drug Administration (FDA) released a pair of orders affecting Hepatitis C (HCV) antibody screening and diagnostic tools. The move was announced as a proposed order in April 2020 with a total of 13 comments on the proposed orders, including the National Association of State and Territorial AIDS Directors (NASTAD), Hawaii and Washington state Departments of Health, the National Hepatitis Roundtable, and one of the current leading device manufacturers, Abbott.
The final orders reclassify already existing screening and confirmatory blood and plasma testing while also changing the name of acknowledged name of the technology in use from “assay devices” to “tests”. The move is anticipated to reduce the burden in applying for regulatory approval of new tests but also require “special controls” to ensure the quality of testing technologies on the market continue to meet the high safety and accuracy standards they currently meet.
Of note, the FDA considered the impact the new final orders would have on public health initiatives, specifically the National Viral Hepatitis Strategic Plan. Additionally, Abbott’s support comment was relatively brief and contained only the concern for possible product code labeling limitations for potential technologies; suggesting the FDA take a similar approach as taken to combination antibody and antigen testing with regard to HCV as with HIV testing. Abbott’s recommendation in the comment was to merely name the technologies “serological” tests rather than limiting application based on the mechanism of action in the test as both the proposed and final orders did.
NASTAD’s comment highlighted the difficulty in current surveillance efforts as confirming an acute or active HCV infection is a two-step process, of which, the organization claims few providers or patients follow through. NASTAD drew direct and natural and logical conclusions from the Centers for Disease Control and Prevention’s (CDC’s) Viral Hepatitis Surveillance Report, highlighting the public health risk HCV poses and the barriers to more effective surveillance efforts, including the cost and regulatory hurdles for new screening technologies to enter the market. The public health interests commenting requested the FDA consider expanding the final rule to include potential future technologies like over the counter (OTC) antibody tests or screening technologies based on body fluids other than blood and plasma or combination testing technologies targeting multiple types of viral hepatitis or HCV-HIV combination tests. The FDA’s response to comments in the final orders stated the new final order could not go beyond the scope of existing technologies and, as such, would not be able to change the approval pathway for new or emerging technologies.
While the orders represent an encouragement for manufacturers to enter the existing technologies market with regard to HCV screenings, diversifying the field, the announcement does not affect developing or new technologies and the pathways to approval those potential products will need to navigate.
One Shot or Two? Necessity of COVID-19 Vaccination Among People Living with HIV and/or Chronic Liver Disease
At the time of this writing, the United States’ Food and Drug Administration (FDA) has provided Emergency Use Authorizations (EUAs) to 3 COVID-19 vaccines, with Novavax’s product potentially leading the race to become the fourth. While some have fretted over “which vaccine” is “the best”, governors and clinicians have resoundingly adopted a simple answer: “which ever vaccine you can get”. While President Biden has pushed to expand eligibility to all adults in the US by May 1st, as we’re all too familiar with in patient advocacy, eligibility does not necessarily equate to access and, in this respect, demand still vastly outstrips vaccine supply domestically.
The debate on who should get a vaccine and when began well before the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations in December 2020. ACIP’s recommendations focused primarily on constructing an ethical model based on hospitalizations and mortality, with an eye toward those performing duties most necessary to meet the health care demands of the moment. Ultimately, outside of this job-based prioritization, ACIP gave top priority via age-based allocation and then ascertaining those at-risk for these outcomes based on pre-existing conditions. Most states adopted some version of these prioritized populations. The debate on the efficacy of this model continues to rage on – what about those in marginalized communities more impacted by COVID-19 than more affluent communities? What about younger people with comorbidities? Which health conditions should be prioritized?
Regardless of where one’s local government falls on this debate, evidence catalogued by the CDC indicates a very real need for people living with HIV and those with chronic liver diseases to seek a vaccine as readily as possible as these cohorts are at increased risk for complications related to a COVID-19 infection. Studies have found PLWH experiencing an acute COVID-19 infection may see as much as 50% drop in CD4 T-cells compared to their historical levels, a condition known as lymphopenia – of which, is also an indicator for severe COVID-19 and protracted recovery or death. Additionally, the same study found key clinical metrics used to measure inflammation were similarly increased among PLWH. Another study out of Wuhan, examining people with chronic, yet controlled Hepatitis B infections may see a reactivation of viral activity and/or potentially face significant progression of liver cirrhosis during and after a COVID-19 diagnosis. Another study found SARS-CoV-2 may target certain cells in the bile tract and cause focused damage to the systems serving a person’s liver, with another study suggesting the need for health care providers to emphasize liver repair post COVID diagnosis.
While Janssen ensured PLWH were enrolled in phase 3 clinical trials for their product, none of the currently authorized products included solid organ transplant recipients in their trials. While the American Society of Transplantation notes COVID-19 vaccine administration recommendations for solid organ transplant recipients remains the same as other vaccines (either completed at least 2 weeks prior to transplant or initiated at least 1 month after transplant). Which may pose a problem according to a study published in March showing transplant recipients having received the first shot in the series mounted an antibody response just 17% of the time. While antibody responses are not necessary to confer immunity, they are the leading indication of an immune response. The authors of this study will be seeking to answer that question later this year.
Furthermore, additional research is needed in assessing post-acute COVID-19 infections and the implications of “long COVID”. Most research at this moment on long-COVID is tied to assessing symptom presentation and frequency of health care needs. However, there is a minor bit of information regarding organ function post-hospitalization with COVID-19 – none of it is “good news”. In particular, people experiencing chronic liver diseases were almost 2 times as likely to experience “major adverse events” after being released from the hospital due to COVID-19.
All of this information culminates with a sense of urgency some states are heeding in expanding vaccine access “ahead of schedule” to include people living with HIV or specific programming targeted to provide vaccines to these communities.
Brandon Macsata, CEO of ADAP Advocacy Association, recently penned a blog addressing any hesitancy among people living with HIV around getting their vaccines: “Vaccines are an important element of the journey, along with proven public health strategies (i.e., wearing masks, remaining social distant, washing hands). For the HIV-positive community, it is even more important for us to do our collective part to protect ourselves, as well as the people around us. Get your Covid-19 vaccine!”
With the CDC’s guidance on prioritizing our communities in vaccination schemes, I couldn’t agree more.
The Future is Now: Welcome to the Age of Injectables
For years, HIV advocates have anticipated injectable antiretroviral therapies (ART) – often with a level of excitement. I recall listening to robust discussions between advocates and officials in statewide meetings, reviewing candidate treatments, discussing labor and staffing needs for providers, potential regulatory changes needed to ensure programs could cover the actual syringes associated with injectable ART, given state-based restrictions. The excitement extended from a sense of no longer needing daily tablets (pills) in order to maintain adherence and thus an undetectable viral load, extend quality of life for those experiencing barriers to care like homelessness, and otherwise welcome a new age of treatment – if only by new method of delivery.
In late 2019, we seemed on the edge of such an accomplishment. ART focused pharmaceutical manufacturers Glaxo Smith Kline subsidiary, ViiV, and Johnson & Johnson subsidiary, Janssen, had paired up in an effort to provide the world with its first long-acting ART via injection. However, the Food and Drug Administration (FDA) refused to grant the companies an approval for the dual shot regimen of cabotegravir and rilpivirine (together, “Cabenuva”) due to concerns related to “Chemistry Manufacturing and Controls”. Thirteen months later, on January 21, 2021, Janssen and ViiV announced FDA approval of Cabenuva.
ViiV Healthcare understands the transformative nature of Cabenuva and the many “firsts” associated with a provider-administered injectable therapy for HIV. We will be educating HCPs on how to identify appropriate patients who may prefer or benefit from an option other than daily, oral therapy. Two key considerations are that patients agree to the required monthly dosing schedule and understand the importance of adherence to scheduled dosing visits. We also will be helping educate people living with HIV about Cabenuva and these commitments. - ViiV
According to the product monograph, Cabenuva is a dual intramuscular injection protocol (requiring one shot of cabotegravir and one shot of rilpivirine) monthly, administered by a health care provider. Prior to starting the monthly injections, providers should test tolerability via “oral lead-in” via once daily tablets of both cabotegravir and rilpivirine with a meal. If consumers expect to miss a monthly injection by more than 7 days, once daily oral tablets of cabotegravir and rilpivirine may be used to replace the injections for up to two injection cycles (or 2 months). Contraindictions include any known or suspected resistance to either or both drugs and any intolerability of components of either or both drugs. The injections cannot, at this time, be self-administered.
Despite all of the antici…pation and data showing a higher level of satisfaction than with current regimens among trial participants, some advocates are still cautious and concerns remain regarding logistical accessibility. Regarding financial accessibility, ViiV has already launched its patient assistance program for Cabenuva through ViiVConnect. Florida advocates and members of Florida HIV/AIDS Advocacy Network, Ken Barger, Joey Wynn, and David Brakebill, discussed in…spirited detail varying perspectives on rural access.
Wynn advocated for diversifying public funds, if rural health departments couldn’t meet the demand of a once monthly injection protocol, “If a rural health department can’t do a monthly injection [for ART], when they do injections for all sorts of other disease states, they need to give their money to providers who can.” Barger and Brakebill pointed out that for many rural counties, the health department may be the only provider in the area that’s accessible, with a highlight on concern regarding capacity. Wynn suggested the need for investment in better planning and preparation – not just for injectables, but for situations of natural disasters which have been known to disrupt access to medications and care in the state regularly.
When asked about these concerns, ViiV acknowledged the challenges and provided the following commitment to invest in ensuring more equitable access to care: ViiV Healthcare is also dedicated to improving how HIV treatment and care are delivered in the “real-world” environment through our Implementation Science program. One example of this focus is a study evaluating how improvements in transportation and use of digital tools can help get people living with HIV to their healthcare providers on a regular basis, which if successful we’ll look to implement on a broader scale
This week’s HEAL blog wouldn’t have been possible without the coverage of and reporting on treatment developments in this and other therapeutic areas by Liz Highleyman.
Quotes attributed to ViiV Healthcare are direct and were provided by Robin Gaitens, Product Communications Director.