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Zynteglo May Herald “New Dawn” of Many Seven-Figure Gene Therapies


An OptumRx drug pipeline report highlights Zynteglo, a curative gene therapy treatment for beta-thalassemia, and Skysona, a gene therapy for a cerebral adrenoleukodystrophy. FDA approval decision are imminent for both. Price tags of $2 million are expected.

Two gene therapies, one of them curative and both likely to have price tags of more than $2 million, are on the drug pipeline report issued this week by OptumRx, UnitedHealth Group’s pharmacy benefit management (PBM) division.

The PBM also put teclistamab, a bispecific antibody that is treatment relapsed or refractory multiple myeloma, and deucravacitinib, an oral drug used to treat plaque psoriasis, on its list.

Bill Dreitlein, senior director, pipeline and drug surveillance for OptumRx, said in written comments sent to Managed Healthcare Executive® that Zynteglo (betibeglogene autotemcel), one of the two gene therapies, may have the biggest clinical impact of the drugs that the PBM is spotlight.

Zynteglo is a treatment for beta-thalassemia, a rare genetic that results in low levels of hemoglobin, the protein in red blood cells that ferries oxygen throughout the body. Between 1,000 and 1,500 people in the U.S. have a form of beta thalassemia that is treated with lifelong blood transfusions and chelation therapy to prevent the build- up of iron from those infusions. Zynteglo would be a one-time treatment, replacing the need for transfusions and chelation, that involves modifying the patient’s own stem cells so they become a source working versions of the dysfunctional genes that cause the beta thalassemia.

“The possibility of addressing the underlying cause of anemia in this disease and eliminating the need for blood transfusions as well as the chelation therapy needed to manage the side effects of the blood transfusion is quite attractive,” Dreitlein.

The approval process and rollout for Zynteglo has been bumpy. The FDA put a clinical hold on trials last year after results from other trials linked the viral vector it uses to blood cancer. It was approved by European drug regulators in 2019 but its use was delayed because of the COVID-19 pandemic.

But the prospects for Zynteglo and the company that developed it, Bluebird bio, a Somerville, Massachusetts, biotech company, have brightened this spring summer. In May, the Institute for Clinical and Economic Review (ICER), an independent cost-effectiveness group, issued a favorable review of Zynteglo. The review gave the treatment a B+ rating and said the anticipated price of $2.l million met ICER’s health benefit benchmarks with an 80% payback option for patients who are not cured and continue to need transfusions. According to clinical trial result summaries by ICER and OptumRx, 90% of the patients treated with Zynteglo in phase 3 trials no longer needed blood transfusions.

About a month after the ICER review, an FDA advisory panel of outside experts voted 13-0 in favor of approving Zynteglo. The FDA is scheduled to announce its final approval decision on Zynteglo on Aug. 19.

How insurers and self-insured employers are going to manage cost of gene therapies with seven-figure price tags is an open question. Dreitlein pointed out that there is precedent for treatments with annual costs that add up to more than $1 million. “It’s not uncommon to spend over seven figures to treat some hemophilia patients per year,” he noted. But he acknowledged that Zynteglo and Skysona (elivaldogene autotemcel), the other gene therapy highlighted by OptumRx that is a treatment for cerebral adrenoleukodystrophy, are part of “new dawn of genetic therapies that will cost upwards of $1 million per treatment” that pose payment challenges.

Dreitlein said OptumRx is selling gene therapy risk protection coverage involves paying a flat per member, per month to pay for the cost of gene therapies. In his written comments, he described it as “a risk-bearing product designed to provide patients appropriate access to ultra-high-cost gene therapies while helping plan sponsors manage the financial risk and volatility these therapies pose.”

Here is a rundown of the other drugs discussed in the OptumRx pipeline report:


As mentioned above, teclistamab is a bispecific antibody that recognizes the B-cell maturation antigen (BCMA) on multiple myeloma cells and CD3, a T-cell receptor. Like other bispecific antibodies, by recognizing both the cancer cells and the T cells, it is designed to conscript T cells into the business of cancer cells — in this case, multiple myeloma cells expressing BCMA.

According to the OptumRx report, teclistamab would join Blenrep (belantamab) and two CAR-T cell therapies, Carvykti (ciltacabtagene autoleucel)and Abecma (idecabtagene vicleucel) as multiple myeloma treatments that home in on BCMA-expressing cells. There are no head-to-heads trials but the report says that indirect evidence from clinical trials suggests that the newcomer teclistamab, a Johnson & Johnson product, appears to more effective than Blenrep, a GSK product, but less effective than the CAR-T. But according to the OptumRx report, there is a trade-off because the CAR-T therapies are associated with a greater chance of cytokine release syndrome, which can be fatal, and neurotoxicity than treatment with teclistamab.

The report says Johnson & Johnson hasn’t posted a price for teclistamab but noted that Blenrep’s wholesale acquisition cost is approximately $17,000.

The report says results from the main clinical trial of teclistamab showed an overall response rate of 63% after a median follow-up period of 14.1 months.

The report says the FDA is expected to announce on Aug. 29 whether it has approved teclistamab.

Dreitlein said several other bispecific antibody therapies for multiple myeloma are in late-stage development, including another Johnson & Johnson product, talquetamab; Pfizer’s elranatamaband Regeneron’s REGN5458.

Dreitlein noted that bispecific antibodies and CAR-T therapy are both immunotherapies that recruit the immune system into attacking cancer, but the current version of CAR-T requires collecting and re-engineering the patient’s own cells in a bespoke fashion. “The big advantage of for bispecifics is that they are ‘off the shelf’ therapy that is ready to administer immediately,” wrote Dreitlein. 


Deucravacitinib is an oral drug that has been developed as a treatment for moderate-to-severe plaque psoriasis, an autoimmune disrorder that affects the skin. According to the OptumRx report, there’s evidence that deucravacitinib is more effective than Otezla (apremilast), an oral drug that targets a different aspect of the autoimmune pathology. Deucravacitinib was also associated with a “numerically lower rate of discontinuations,” according to OptumRx.

However, the report say that indirect evidence suggests that the response rates are better for injectable biologics, so deucravacitinib is likely to slot in as a competitor Otezla rather than the injectable biologics. The annual wholesale acquisition for Otezla is $48,000, so deucravacitinib might be similarly priced.

The FDA is expected to announce whether it has approved the drug on Sept. 10.

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