By Yi Liu, PhD, Senior Analyst; Kelly Cockerill, Director; Carrie Jones, Vice President; and Wyatt Gotbetter, Partner
- As global healthcare systems are diverted to focus on the COVID-19 pandemic, people with rare diseases are particularly impacted.
- In addition to the increased risk of severe disease due to compromised immune systems for many, these patients and the manufacturers of their therapies are facing challenges including ensuring patient access to therapy, setbacks in research efforts, and worries about supply.
- To mitigate the impact of these challenges, there is urgent need for all stakeholders to work together and push forward near-and long-term solutions.
- For manufacturers, opportunities exist to evolve to offer new models of patient assistance and home-care enabling technologies, take novel approaches to clinical trials, and renew focus on collaborating to bolster supply chain.
Rare disease patients are inevitably facing multiple hardships due to the COVID-19 pandemic. While this list is by no means exhaustive, some of the top challenges include:
Meanwhile, manufacturers are investing significantly to overcome access hurdles and fortify supply chains and trials, while facing potential setbacks in cash flow which could impact their ability to invest in development going forward.
Access to Treatment
In a survey of >700 US patients and caregivers presented by NORD, an umbrella coalition of 280 rare disease patient advocacy groups, at least 39% have had challenges accessing medical care.
(1) Access – Reduced Availability and Safety Risks of Visiting Healthcare Providers
As the healthcare system is overloaded and social distancing is recommended to manage infection risks, rare disease patients may encounter:
- Reduced access to specialists: Check-ups and regular supportive care visits are being disrupted, interrupting the momentum of ongoing care and removing the support network that is so important to patient outcomes and experience. In the US and elsewhere, rare disease specialists are often based in hospital centers, which have been largely shut down for non-urgent non-COVID-19 cases.
- Delay in diagnosis: Extending wait lists or putting off visits to meet with specialists could extend a diagnostic odyssey that is already long.
- Treatment interruption: Patients and physicians might choose to delay starting or decrease the frequency of office-infused or intrathecally administered therapy for a number of reasons. Treatment may be disrupted if a patient is quarantined or has an especially high infection risk, if centers are unable to offer the normal capacity of services, or if patients are social distancing away from their usual providers. Since more than 200 drugs delivered via an IV for at least one orphan indication have been approved in the US, this impact could be widespread.
Looking at just a few examples from rare disease companies with significant revenue expected from IV therapies, these manufacturers have noted the potential for reduced patient starts and compliance and lower revenue expectations. To overcome treatment disruptions these companies are also expecting an accelerating shift to home options and placing higher investments in patient support.
Which patients could be most affected by these treatment interruptions? The impact depends on several factors, such as the drug’s dosing and the patient’s status.
For instance, typically a first IV dose needs to be administered in a clinical setting to monitor for adverse events, such as anaphylaxis, and thus COVID-19 is particularly impacting IV new patient starts.
Delays in treatment are especially concerning in diseases that are severe, have high risk of flares, or rapidly progressing.
(2) Access – Hurdles to Home Treatment
Although we are seeing an increase in home infusion, and CMS has announced some flexibility in home health benefits in light of COVID-19, the National Home Infusion Association (NHIA) and over 160 stakeholders are supporting concept legislation that would even further expand access to home infusion for Medicare patients. In addition, not all situations are amenable to home IV administration, especially where management of anaphylaxis risk is a consideration.
(3) Access – Economic Barriers
Moreover, patients are increasingly having difficulty accessing therapy due to socioeconomic reasons. As noted above, 40% of surveyed rare disease patients had been affected by loss of income and 11% had lost insurance coverage, some of whom may no longer be able to pay for treatment. As well, if a patient must change insurers, there may be a delay to accessing coverage with the new plan.
Rare Disease Research Setbacks
In addition to access issues, research setbacks could pressure the innovation pipeline due to:
(1) Disease Research Disruption
Slowing in funding and interruptions in disease research activities, including data collection for registries, natural history, and observational studies could cause delays in critical progress in disease pathophysiology and progression research. Several rare disease patient advocacy and research organizations are citing a critical dearth of donations.
- ALS Therapy Development Institute has noted that COVID-19 is seriously impacting the progress of its research due to inability for some scientists to go into the lab, decline in individual donations, and cancellation of fundraising events. “Without immediate help, we will be forced to pause some of our most promising research projects.”
- Similarly, JDRF is experiencing some project slowdown due to lack of lab access and is voicing the need for more aggressive fundraising to support the community. And outside of rare disease, the Michael J Fox Foundation for Parkinson’s Disease research has temporarily suspended shipping of biosamples for research projects and has provided investigators a 6 month no-cost extension to currently funded projects.
(2) Clinical Trial Hurdles
Lack of access to trial sites is causing hurdles, including: it may take longer to activate new clinical trial sites due to challenges in bringing in patients and diversion of resources and priorities in the provider community, which could lead to some delays. For clinical studies that are ongoing, trial sponsors and service providers are ramping efforts to minimize risk to trial integrity by working closely with trial sites and regulators to assure the safety of trial participants, maintain compliance with good clinical practice, and overcome any data collection challenges.
Coordinated efforts to overcome these hurdles will be critical since many rare diseases are severe, often without standards of care, and thus time is very valuable.
(3) Reduced Funding for Rare Disease R&D
While it is still early to assess the impact of COVID-19 on companies’ financials, the contraction in financial markets, decrease in product revenue, and trial delays could make manufacturer access to capital for R&D more challenging. Although some manufacturers cited revenue gains this quarter from increased stocking of drug in channels – as noted above several have lowered their revenue guidance expectations by 5% for 2020 due to COVID-19, in some cases resulting in projected losses of more than $100MM.
Furthermore, one can speculate that the economic downturn will cause a decrease in total fundraising dollars, and that scientific grant-making agencies, NGOs and philanthropies that support medical research may shift priorities toward the pandemic and more top-of-mind priorities in the near-term.
Supply Chain – Risk of Shortages
Several rare disease therapies may be facing risk of shortages, such as ones that are human-derived (e.g., plasma, blood factors, and cell therapies), being studied as treatments for COVID-19, or that have complex supply chains.
For example, Immunoglobulin (Ig) is derived from human plasma and is used to treat critical illnesses such as primary immune deficiency, ITP, myasthenia gravis, and others. It has faced shortages in the US and other parts of the world for some time, and the problem might be exacerbated during this global crisis. According to the FDA, the number of blood donations has been significantly reduced due to social distancing and the cancellation of blood drives. Additionally, in a time that infectious disease and transmission prevention is on everybody’s mind, there is more pressure to screen blood donation patients and ensure safety protocols, adding more burden to systems that are already over-stretched.
Treatments being studied for COVID-19
As the world doubles down on the war against COVID-19, it has been extremely exciting to see the potential for rare disease therapies to help treat the virus. However, NORD and 95 other nonprofit groups have noted this renewed interest will make it increasingly important to ensure “a consistent supply for people who take an approved medication that is being studied for use in COVID-19.” As an example, hydroxychloroquine, which is used to treat lupus and rheumatoid arthritis, initially had garnered some interest as a COVID-19 treatment and as a result, has now been added to the FDA’s shortage website. Similarly, as plasma-product companies are working to develop plasma COVID-19 therapies, it will be critical to monitor the pressure on plasma supply. For more information, please see our blog on protective antibody therapy for COVID-19.
Complex supply chains
Other complex therapies such as CAR-T with elaborate supply chains have had to act fast to avoid supply delays. For example, to manufacture Novartis’ Kymriah for B-cell acute lymphoblastic leukemia, blood must be taken from a patient, cryopreserved, shipped to a manufacturing facility (initially in New Jersey, now expanded to Switzerland), and then shipped back for infusion into the patient, all in the shortest time possible. During travel restrictions, Novartis was able to quickly make special provisions to bring Kymriah from Europe.
Luckily, many rare disease companies have announced their ongoing intensive efforts to ensure manufacturing, protect the integrity of supply chains, and to stock inventory.
Solutions and Opportunities
While we are facing many negative impacts of COVID-19, with problems come opportunities for solutions and for drug manufacturers and rare disease communities and stakeholders to collaborate during and after this crisis.
In the last few weeks, manufacturers and patient organizations have leapt to the call to help ensure access for patients through increased customer service and financial investment.
- The National Organization for Rare Disorders (NORD) has launched the COVID-19 Critical Relief Program to provide financial assistance to rare disease patients affected by the pandemic to support their critical, non-medical needs.
- Many companies have contributed to rare disease community support, including Alexion, Horizon Therapeutics, Sanofi, Alnylam, and others.
- Moreover, manufacturers have been putting extra effort into navigating patient issues in real-time through expanded patient support programs to help patients move to home-infusion, find funding, etc. Takeda, Bristol Myers Squibb, Novartis, Merck, and others have announced more robust patient services that include high-touch streamlined support and expanded programs to improve affordability (such as vouchers to assist with continuity of care and co-pays, improved access to free treatment, etc.).
Home-care Enabling Technologies and Services
(1) Novel Drug Delivery Devices and Formulations
While interest to improve infusion burden has existed for some time, now the need to extend dosing frequency or enable self-administration is even higher. We anticipate more prioritization of strategies and products that enable home-based therapy. For instance:
Companies continue to launch products with improved dosing schedules, and some have been trialing high volume and novel drug delivery devices that will enable patient self-administration.
- Alexion recently launched Ultomiris, a bi-monthly version of its established drug Soliris. The company has noted in some hotspot areas they’ve seen an acceleration in conversion to Ultomiris due to COVID-19. In addition, Alexion is conducting a phase III trial of Soliris in West’s SmartDose drug delivery platform to enable a once-weekly subcutaneous infusion at home.
- In PAH (Pulmonary Arterial Hypertension), United Therapeutics is trialing a drug-device combination product that combines a disposable PatchPump® technology with Treyvent to ease continuous subcutaneous infusion.
Drug delivery platforms such as Halozyme’s ENHANZE technology enable subcutaneous dosing of drugs previously delivered via high volume IV administration.
- Hyqvia, a subcutaneous reformulation of immunoglobulin (Ig) therapy was approved in 2014 using Halozyme’s technology.
- More recently on May 1, the FDA approved Johnson and Johnson’s Darzalex FasPro, a subcutaneous version of the IV treatment for multiple myeloma that cuts down on injection time and infusion-related side effects.
- Similarly, Xeris is leveraging its novel platform to develop and commercialize room-temperature stable formulations that can make injections easier or reduce the need for IV. Its first product, a stable glucagon for Type 1 diabetes, was approved in 2019 and the company also aims to improve treatment delivery for rare epilepsy.
The COVID-19 dynamic may help increase the perceived value and uptake of these drug delivery innovations.
(2) Homecare-Enabling Services
Similarly, in a move to help relieve hospital capacity issues due to rising COVID-19 cases and infection risk, services such as home infusion and telemedicine are increasingly being utilized. For example, CVS Health has announced that it will provide in-home nursing services to support the transition to eligible IV-therapy patients out of the hospital. Barry Greene, the president of Alnylam Pharmaceuticals, recently noted that “home infusion has become broadly available in most countries, thanks in part to the recognition of value by physicians, payers, and regulators.” Opportunity exists for policy initiatives to expand access even further.
In addition, the patient-physician interactions have shifted from in-person to virtual, leading to a rise in the use of telemedicine. For more information about the impact of COVID-19 on digital health including virtual visits, digital symptom checkers, and remote patient monitoring, please refer to Health Advances recent blogs on the impact of COVID-19 on digital health and telemedicine in the US, Europe, and Asia Pacific.
Clinical Trial Decentralization and Real-World Evidence
To improve patient access and enrollment in clinical studies during the pandemic, the need for clinical trial decentralization has been accelerated. Rare disease drug developers and their CRO partners are rethinking the future of how clinical trials are conducted and embracing either fully virtual or hybrid approaches to shift to decentralizing models. The FDA has put out guidance that shows flexibility in clinical trials and opens the door for methods to keep research going by including virtual visits, phone interviews, self-administration, and remote monitoring.
These changes provide an opportunity to accelerate the role real-world evidence plays in the development of novel orphan drugs. To seize the opportunity, companies will need to work with disease stakeholders, such as patients and caregivers, key opinion leaders, healthcare workers, payers, and regulators, to design effective trials with meaningful endpoints and ensure robust and standardized data collection.
Revitalized Focus on the Supply Chain
As patients that need plasma therapies for chronic diseases are facing a great deal of uncertainty and increased health risks, stakeholders are and will need to continue to band together to ensure supply. These efforts are underway as:
- Healthcare authorities are stressing the importance of becoming a blood donor during this critical period. The U.S. Department of Homeland Security guidelines have designated the plasma industry an “Essential Business” during this pandemic to ensure uninterrupted supply chain.
- Patient advocacy groups are utilizing social media to highlight the importance of the plasma therapeutics industry and its workforce and to promote the importance of becoming a plasma donor.
- Manufacturers such as the CoVIg-19 Plasma Alliance member companies operate more than 500 plasma collection centers in the U.S. alone, enabling close access to a center to more than 50% of the eligible donor population. The alliance has also been ramping up collection in more European countries such as Austria, Czechia, Germany, and Hungary to accommodate the new COVID-19 research. Other key plasma therapy manufacturers such as Grifols have prioritized maintaining operation in its plasma centers, industrial and commercial sites to continue production through the crisis.
Going forward, coordinated efforts to increase blood donation and plasma collection will be critical.
Many other aspects of supply chain may be impacted and reformed by COVID-19 – please see Health Advances’ upcoming commentary on the impact of COVID-19 on supply chain by subscribing to our blog.
As we face the challenges caused by the global pandemic, it is crucial to keep in mind that access to therapies and continued funding of drug development, translational research, and basic research is critical to saving lives for rare disease patients. It is imperative, now more than ever, to increase communication and collaboration across the patient advocacy, healthcare provider, researchers and manufacturers and work with regulators and payers to forge paths forward. We are hopeful that as the rare disease community comes together to develop pragmatic solutions for the challenges exacerbated by the COVID-19 crisis, new best demonstrated practices and innovations will emerge and have a lasting impact on the advancement of and access to novel life-changing therapies for rare disease patients even after the pandemic resolves.
The very essential nature of rare disease therapies helps to ensure continuity of care for patients and funding for therapy sponsors, as shown in our Resiliency Index, which assessed what types of treatments were most resilient after the 2008 recession. Thus, we remain optimistic for the continuing innovation and life-saving technologies coming forth from the biopharma industry.