Hemophilia Gene Therapies Face Market Struggles Despite Scientific Promise
Key Insights
Hemophilia gene therapies are underperforming commercially despite initial blockbuster expectations, with Pfizer withdrawing Beqvez from the market and BioMarin seeking to divest Roctavian.
High treatment costs, including Hemgenix's $3.5 million price tag, create reimbursement challenges as payers question covering lifetime therapies for patients who may switch plans within two years.
Structural disincentives discourage adoption, with treatment centers potentially losing $500,000-$750,000 annually in revenue when patients switch to gene therapy.
Hemophilia gene therapies arrived with blockbuster expectations but are now struggling commercially, with one treatment withdrawn from the market and others facing significant reimbursement challenges. Despite representing major scientific advances, these one-time treatments are encountering barriers that limit their adoption in clinical practice.
Commercial Disappointments Mount
BioMarin Pharmaceutical's hemophilia A gene therapy Roctavian was predicted by analysts to reach peak sales of $2.2 billion. Instead, the company is now looking to offload the drug due to weak commercial uptake. Similarly, Pfizer has pulled its hemophilia B treatment Beqvez from the market, while CSL Behring's Hemgenix, the first to market, is also significantly underperforming.
"It's a value-laden intervention," said Dr. Michael Recht, chief medical and scientific officer for the National Bleeding Disorders Foundation (search). "It's just shockingly expensive."
The dismal sales surprised many who viewed hemophilia gene therapies as promising one-time alternatives that could free patients from frequent clotting factor infusions or injections.
Price and Reimbursement Barriers
Gene therapies carry substantial price tags, with Hemgenix becoming the world's most expensive drug when approved in 2022 at $3.5 million per dose. Despite the sticker shock, CSL estimates that Hemgenix could save up to $5.8 million per person by eliminating the need for once- or twice-weekly clotting factor injections.
However, payers have balked at covering these treatments. According to Recht, insurers argue that since the average time someone stays on a specific health plan is under two years since the Affordable Care Act, they question paying for lifetime therapy when patients might switch plans quickly.
An NBDF data analysis found that rapid plan hopping is not as common as insurers claim, with people typically only changing plans when they change jobs since the Affordable Care Act's introduction.
Structural Disincentives Complicate Adoption
Beyond reimbursement issues, structural disincentives further complicate gene therapy adoption. The Hemophilia Treatment Center 340B Factor Program offers certified organizations discounts for medications and supplies, allowing centers to reinvest savings into facility programs.
However, gene therapy payments typically go to hospitals rather than treatment centers. "So the hospital would get all the income from the gene therapy, and the treatment center could lose $500,000 to $750,000 a year in revenues from someone on prophylaxis," Recht explained.
This financial structure discourages treatment centers from recommending gene therapy. "To me, that is not a compelling reason at all, and potentially an unethical reason if this is the right drug [for a patient]," Recht said. "But this is what I've heard from some of my colleagues."
Patient Selection and Treatment Challenges
While gene therapy isn't optimal for all patients, it could benefit a subset. Many patients can afford a wait-and-see approach because other treatments remain effective.
"There are some really great non-gene therapy options for people with hemophilia A," Recht noted. "[Hemlibra] is a great drug, and has changed the way I've treated people."
Patient eligibility also limits market potential. Hemgenix targets hemophilia B, which comprises only about 15% of overall cases, and excludes children and patients with certain liver conditions.
For Beqvez, market obstacles proved insurmountable. "I think Pfizer's [Beqvez] was a perfectly good product," Recht said. "But as the second to market with the results of their phase 3 maybe not as robust as the Hemgenix clinical trial, I think that played a big role."
Roctavian faces durability concerns despite targeting a broader hemophilia A patient population. "The durability is the biggest issue," Recht said, though recent data showed the treatment remained effective after five years. "To get 10 years of not having hemophilia, that's still 10 years of not having hemophilia."
Innovation Continues Despite Market Struggles
Despite current market challenges, the hemophilia treatment landscape remains promising. "I'm very hopeful there will be products to address the unmet needs of the inheritable bleeding disorders population," Recht said.
Novo Nordisk recently submitted an application for Mim8, which Recht predicts could match Hemlibra's safety and efficacy while potentially appealing more to patients through its pen injector delivery method.
Interest in gene therapy persists among companies seeking market entry. Be Biopharma (search) is conducting Phase 1 trials with BE-101, a cell therapy that places vectors into patients' own B cells. "The fascinating part about this is if this is safe and it works, it will be re-dosable because you won't have an immune response like you do with an adeno-associated virus vector," Recht explained.
Startups are also testing gene editing approaches for hemophilia, though many treatments remain years from reaching patients. While determining optimal uses for existing medications presents ongoing challenges, patients now have more treatment options than ever before.