Unexpected impacts of COVID-19 go deep in health care, affecting the progress of gene therapy

The impact of COVID-19 on our country has been deep and profound. In the U.S. alone, it has caused more than 947,000 deaths and 78 million cases.¹ COVID-19’s influence throughout health care will take years to fully understand. One surprising effect was the slowdown in gene therapy development.

At Prime Therapeutics (Prime), we prepare our clients to manage new drugs by closely following the drug pipeline, which includes high cost gene therapy drugs. Many of these gene therapies have had their progress delayed at various stages of development because of the COVID-19 pandemic. According to a 2020 survey by analytics firm GlobalData, 59 gene therapy clinical trials involving 80 drugs and 63 companies were delayed due to the pandemic. The main reasons cited for the slowdowns were that hospitals were overwhelmed and lockdown measures limited patient access to clinical trials.²

Other impacts on the industry ran from research to rollout

Research: Research labs shut down or reduced staffing for safety. Research and preclinical facilities were impacted by worldwide high demand for personal protective equipment and reagents.³ This meant slowdowns in research. And the GlobalData survey reported that 43% of those gene therapy companies were likely to need an influx of new funds in the next 12 to 24 months to progress further. Of those needing more funding, 44% were in Phase 2 trials.⁴

 Definition: Viruses are germs. They are designed to invade living, normal cells and then multiply to cause infectious disease. Gene therapy uses a virus’s natural ability to deliver genetic material into cells. Before a virus can be used to carry therapeutic genes into human cells, it must be modified. It is stripped of the parts that can cause an infectious disease. Then it becomes a viral vector.⁵

Manufacturing/supply chains. Manufacturers of gene therapies use viral vectors. The vaccine industry also uses viral vectors. Much of the raw material used to manufacturer viral vectors were quickly diverted to companies working on what they hoped would be billions of doses of COVID-19 vaccines.⁶ This caused a shortage for manufacturers of gene therapies.

Access to patients and hospitals: Hospitals concerned about the transmission of COVID-19 canceled or delayed appointments. And many patients were unable to visit treatment centers because of travel bans. Many treatment centers were no longer available for treatments or appointments because they had restrictions on non-urgent care.³ It was a perfect storm of delayed access.

Recruiting and trials: Half of cell and gene therapy companies found it more difficult to recruit patients for trials. Many of them suspended trials. The pandemic impacted follow-up assessments for patients already enrolled in trials. This made record keeping problematic and inconsistent.³

Prime announced its PreserveRx^sm gene therapy reinsurance product two years ago. PreserveRx launched early in COVID-19’s spread across the United States. This unique reinsurance product was designed to protect both health plans and employers from sudden, one-time costs due to covering ultra-expensive gene therapies.

PreserveRx was released to support the only two gene therapies available at the time, Luxturna^® and Zolgensma^®. And they are still the only two gene therapies available, due to the pandemic. But the announcement proposed support for three additional gene therapies that looked as though they might be approved by the Food and Drug Administration (FDA) in 2020:

• Roctavian™ (valoctocogene roxaparvovec, BMN 270), a treatment for hemophilia A
• LentiGlobin^® (lovotibeglogene autotemcel), a treatment for sickle cell anemia
• PTC-AADC (eladocagene exuparvovec): a treatment for aromatic l-amino acid decarboxylase deficiency (AADC deficiency)

None of those three gene therapy treatments were approved in 2020 or 2021. Roctavian and PTC-AADC have the potential of being approved late in 2022.⁷ Here’s their current status:

• Roctavian, from Biomarin, received a complete response letter (CRL) from the FDA in 2020 asking for further research. Biomarin expects to resubmit in the second quarter of 2022. Roctavian’s anticipated wholesale acquisition cost (WAC) is $2 to $3 million.
• PTC-AADC is manufactured by PTC Therapeutics. PTC recently announced at a health care conference that it expects to submit its biologics license application (BLA) to the FDA in the second quarter of 2022.⁸ Its anticipated WAC is $4 million.

LentiGlobin from bluebell, is expecting to resubmit in the first quarter of 2023. Its anticipated WAC is $1 million.

Definition: BLA, a biologic license application, is submitted with a biologic drug product to the Food and Drug Administration (FDA) requesting approval for manufacturing and distribution. A BLA includes applicant information, product/manufacturing information, pre-clinical studies, clinical studies and labeling.

Prime is monitoring two other gene therapies in the pipeline that do have PDUFA dates in 2022:⁹

• The gene therapy betibeglogene autotemcel (beti-cel), from bluebird Bio has a PDFUA date in August 2022. It treats transfusion-dependent beta-thalassemia (TDT) This is a severe genetic blood disorder that makes it difficult for red blood cells to carry oxygen.⁸ The most severe cases require regular blood transfusions, which can also cause a toxic buildup of iron in the blood.
• The gene therapy elivaldogene autotemcel, also from bluebird bio, has a PDUFA date in September 2022. It treats childhood cerebral adrenoleukodystrophy. This is a very rare genetic disease primarily affecting young boys. It causes progressive damage to the brain, leading to the permanent loss of physical and cognitive function, and it is often fatal.

Definition: PDFUA stands for the Prescription Drug User Fee Act (PDUFA), created by Congress in 1992. It authorizes FDA to collect user fees from drug companies as part of expediting the drug approval process. Over time, the acronym and shorthand, PDUFA date, has come to refer to the scheduled date when the FDA will announce its decision on whether a drug is approved or not.

PreserveRx will continue to be a leading solution

PreserveRx was the industry’s first reinsurance product to covering gene therapies. PreserveRx Insurance is a unique clinical and financial solution, specifically designed to reinsure high-cost gene therapies for payers. It covers gene therapies to help preserve member access and coverage for these life-altering therapies. PreserveRx will be expanded to include additional FDA approved gene therapies.

At Prime, we strive for financial protection, backed by clinical intelligence, to reduce the risks from high-cost gene therapy.

---

References

1. https://covid.cdc.gov/covid-data-tracker/#datatracker-home
2. Covid-19 Forces Gene Therapy Companies to Shift Strategy. July 29, 2020. By Victor Kotsev. LAbiotech.eu. Accessed at: https://www.labiotech.eu/trends-news/covid-19-gene-therapy-shift/
3. Loche, Alberto; Mossmann, Waltraut; Van der Vekenn, Lieven; Yang, Guang. COVID-19 and cell and gene therapy: How to keep innovation on track. August 18, 2020. © 1996-2022 McKinsey & Company. Accessed at: https://www.mckinsey.com/industries/life-sciences/our-insights/covid-19-and-cell-and-gene-therapy-how-to-keep-innovation-on-track#
4. Qiu T, Wang Y, Liang S, Han R, Toumi M. The impact of COVID-19 on the cell and gene therapies industry: Disruptions, opportunities, and future prospects. Drug Discov Today. Published online 2021 Apr 21. 2021;26(10):2269-2281. doi:10.1016/j.drudis.2021.04.020. Accessed at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057929/
5. https://medlineplus.gov/viralinfections.html
6. eu. Covid-19 forces gene therapy companies to shift strategy. www.labiotech.eu/gene-cell-therapy/covid-19-gene-therapy-shift/, Published July 29, 2020. Accessed April 13, 2021
7. PTC Therapeutics Provides an Update on Commercial Progress and R&D Pipeline at 40th Annual J.P. Morgan Healthcare Conference, Jan 20, 2022. Accessed at: https://ir.ptcbio.com/news-releases/news-release-details/ptc-therapeutics-provides-update-commercial-progress-and-rd