Victoria Johnson joined the MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and now HCPLive. You can reach her at vjohnson@mjhlifesciences.com

Victoria Johnson

Pfizer has announced that it is discontinuing development and commercialization of fidanacogene elaparvovec an adeno-associated virus (AAV) vector-based gene therapy for the treatment of hemophilia B.

 The therapy was approved by the FDA under the name Beqvez less than a year ago, in April 2024.

Reuters reported the news on February 21, stating that Pfizer cited limited interest in gene therapies for hemophilia as a reason for discontinuation.

 No patients had been dosed yet in the commercial setting with the therapy, which was priced at a whopping $3.5 million.

The last data Pfizer reported on fidanacogene elaparvovec were presented at December’s American Society of Hematology meeting by Ben Samelson-Jones, MD, PhD, assistant professor pediatric hematology, Perelman School of Medicine, University of Pennsylvania and Associate Director, Clinical In Vivo Gene Therapy, Children’s Hospital of Philadelphia.

The data demonstrated favorable safety 5 years out from administration but a slight and continuous degradation in factor IX levels that reflects concerns patients and clinicians in the field have about the long-term durability and efficacy of gene therapy for hemophilia, especially considering that gene therapies are currently a one-and-done, not redosable treatment strategy.

“It should be very reassuring that there's nothing unexpected," Samelson-Jones told HCPLive® during the meeting. “I think the story of AAV-based gene therapy for hemophilia over the last 3 decades has been surprises. And I think what this is should be reassuring, that there's nothing has popped up that it that is of concern.”

The news follows Pfizer’s shift away from gene therapy development, after it discontinued development of fordadistrogene movaparvovec, an investigational AAV gene therapy for the potential treatment of Duchenne muscular dystrophy in July, and more recently, terminated its deal with Sangamo Therapeutics to develop and commercialize giroctocogene fitelparvovec gene therapy, which was also in development for treating hemophilia A.

Other players in the field of hemophilia gene therapy have likely felt similar sentiments toward the treatment strategy since entering the market. Namely, BioMarin has scaled back its efforts with regard to valoctocogene roxaparvovec (Roctavian) hemophilia A gene therapy to center on distribution in the United States, Germany, and Italy, the 3 countries in which it has been approved for use by relevant regulatory authorities and is reimbursed,

 while both val-rox and UniQure and CSL Behring’s hemophilia B gene therapy, etranacogene dezaparvovec (Hemgenix), have reportedly been 

Santhosh C. Pfizer stops commercialization of hemophilia gene therapy Beqvez. Reuters. February 21, 2025. 

https://www.reuters.com/business/healthcare-pharmaceuticals/pfizer-says-it-will-end-global-development-gene-therapy-beqvez-nikkei-reports-2025-02-20/

U.S. FDA Approves Pfizer’s BEQVEZ™ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. News release. Pfizer. April 26, 2024. Accessed April 26, 2024. 

https://www.businesswire.com/news/home/20240425269649/en/U.S.-FDA-Approves-Pfizer%E2%80%99s-BEQVEZ%E2%84%A2-fidanacogene-elaparvovec-dzkt-a-One-Time-Gene-Therapy-for-Adults-with-Hemophilia-B

Samelson-Jones B, Frenzel L, Kavakli K, et al. Use of Fidanacogene Elaparvovec, a Gene Therapy Vector, to Deliver a Stable, Fully Functional Human Factor IX Transgene for the Treatment of Hemophilia B: A Combined Analysis of Safety. Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 3577

Pfizer officially calls it quits on DMD gene therapy, lays off staff at Sanford site. News article. Elizabeth S. Eaton. FirstWordPharma. July 29, 2024. https://firstwordpharma.com/story/5880030

Sangamo Therapeutics to Regain Full Rights to Hemophilia A Gene Therapy Program Following Pfizer’s Decision to Cease Development of Giroctocogene Fitelparvovec. News release. Sangamo Therapeutics. December 30, 2024.

BioMarin Announces Updated Strategy for ROCTAVIAN® to Focus on U.S., Germany and Ital. News release. BioMarin Pharmaceutical Inc. August 5, 2024. Accessed August 15, 2024. 

https://investors.biomarin.com/news/news-details/2024/BioMarin-Announces-Updated-Strategy-for-ROCTAVIAN-to-Focus-on-U.S.-Germany-and-Italy/default.aspx

Articles

Pfizer has ceased the development and commercialization of fidanacogene elaparvovec, a gene therapy for hemophilia B, due to limited market interest. Despite FDA approval in 2024, no patients received the therapy commercially, which was priced at $3.5 million. Data presented at the American Society of Hematology meeting showed favorable safety but concerns over long-term efficacy. This decision aligns with Pfizer's broader shift away from gene therapy, as seen with other discontinued projects. Other companies, like BioMarin, are also adjusting their strategies in the hemophilia gene therapy market.

Fidanacogene elaparvovec was approved under the name Beqvez in April 2024.

Pfizer Drops Approved Hemophilia B Gene Therapy

Dupilumab improved small airway dysfunction (SAD) in people with type 2 high moderate-to-severe 

, possibly explaining improvements in disease control.

These findings, from the phase 4 VESTIGE study (NCT04400318), will be presented at the 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress, February 28-March 3, in San Diego, California, by Brian Lipworth, MD, Professor of Allergy and Pulmonology at University of Dundee.

“SAD measured by airway oscillometry is related to type 2 inflammation and poor asthma control. Here, we present a post hoc analysis of the phase 4 VESTIGE study evaluating the effects of dupilumab using airway oscillometry,” Lipworth and colleagues wrote.

The VESTIGE study enrolled adult patients with uncontrolled type 2 high moderate-to-severe asthma that were randomized to receive dupilumab 300 mg (n = 72) or placebo (n = 37) every 2 weeks for 24 weeks. The study’s endpoints were peripheral airway resistance as heterogeneity between 5 and 20 Hz (R5–R20), peripheral compliance as reactance area (AX) using airway oscillometry (with Thorasys Tremoflo®), and the proportion of patients receiving dupilumab who improve from baseline exceeding the biological variability (BV) for R5–R20 ≥0.04 kPa/L/s and AX ≥0.39 kPa/L compared with placebo.

The investigators found that patients that received dupilumab experienced significant improvements in SAD as measured by peripheral airway resistance and compliance. The dupilumab group had significantly lowered R5–R20 (least squares difference mean [LSM], −0.06 kPa/L/s [95% CI, −0.10 to −0.02]; 

 <.01) and AX (LSM, −1.43 kPa/L [95% CI, −2.45 to −0.40]; 

 <.01) than the placebo group. The dupilumab group was also 73% more likely to improve R5–R20 exceeding BV, with an odds ratio [OR] of 3.7 (95% CI, 1.4-9.7; 

<.01) compared to the placebo group, and 57% more likely to improve AX exceeding BV, with an OR of 2.35 (95% CI, 1.0, 5.5; 

Other recent research on asthma found that inhaled triple therapy (ITT), despite being well known to decrease exacerbation rate and improving lung function for patients with asthma, was still not widely used by clinicians due to uncertainty in implementing it into patients’ treatment regimens.

“The impact of ITT, nowadays recommended for moderate to severe asthma not adequately controlled by at least average doses of inhaled corticosteroids (ICS) combined with long-acting beta-agonists (LABA), remains to be quantified and is an area of active investigation due to its clinical and management implications. In conclusion, the survey identifies certainties and uncertainties among clinicians regarding the use of triple therapy in clinical practice, highlighting the need for further measures to effectively integrate research findings into day-to-day clinical practice,” Bagnasco and colleagues concluded.

Lipworth B, Saralaya D, Zhang M, et al. Dupilumab Produces Clinically Relevant Improvement in Small Airway Dysfunction in Patients With Moderate-to-Severe Asthma: Results From the Phase 4 VESTIGE Study. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 936.

Bagnasco D, Ansotegui I, Baiardini I, et al. Triple inhaled therapy in asthma: Beliefs, behaviours and doubts. 

 2024, 102333(87). doi: 10.1016/j.pupt.2024.102333

Dupilumab has shown efficacy in improving small airway dysfunction (SAD) in patients with type 2 high moderate-to-severe asthma, as demonstrated in the phase 4 VESTIGE study. The study revealed significant improvements in peripheral airway resistance and compliance among patients receiving dupilumab compared to placebo. Additionally, the study highlighted the challenges in the adoption of inhaled triple therapy (ITT) for asthma management, despite its known benefits. The findings underscore the need for further integration of research into clinical practice to optimize asthma treatment strategies.

Dupilumab improved R5–R20 and AX compared to placebo, possibly explaining improvements in disease control.

Dupilumab Improves Small Airway Dysfunction in People With Type 2 Asthma

Mukkamala also discussed the importance of expanding non-opioid pain relief options.

New Buprenorphine Label Allows Physician-Informed Treatment of Opioid Use Disorder, with Bobby Mukkamala, MD

The FDA approved the prior supplement submission for Indivior’s 

buprenorphine extended-release injection 

(SUBLOCADE) to treat opioid use disorder (OUD) this past Monday, February 24, 2025.

The news comes almost 1 year after its initial approval for treating treat moderate to severe OUD

 and expands the approved subcutaneous injection site of the abdomen to the thigh, buttock, and back of the upper arm for induction and maintenance.

Notably, the updated label also reduces treatment induction time from the current 7-day minimum on transmucosal buprenorphine to a single dose of transmucosal buprenorphine with a 1-hour observation period to confirm tolerability and allows patients to receive a second 300 mg dose 1 week after the initial 300 mg injections.

spoke with otolaryngologist Bobby Mukkamala, MD, who is serving as president-elect of the American Medical Association (AMA) and chair of the AMA’s Substance Use and Pain Care Task Force, to learn more about why the labeling change is an important step in treating OUD. He also stressed the importance of adding more non-opioid pain management strategies to the market, such as suzetrigine, which was approved in January 2025.

“Everything changes from year to year, and that number needs to change if we're going to be able to take care of our patients. And that's something that a physician will decide, because they know the patient. They know what the use history is. They know what the need for treatment is, and the amount of that need, is it 24 milligrams? Is it 32 milligrams? That's something that shouldn't be limited by regulations. It should be the decision of the physician,” Mukkamala said.

Indivior Announces FDA Approval of Label Changes for SUBLOCADE® (buprenorphine extended-release) Injection. PR Newswire. February 24, 2025. 

https://www.prnewswire.com/news-releases/indivior-announces-fda-approval-of-label-changes-for-sublocade-buprenorphine-extended-release-injection-302382920.html

Braeburn's BRIXADI™ (buprenorphine) Extended-Release Subcutaneous Injection (CIII) Receives FDA Approval for Moderate to Severe Opioid Use Disorder. PR Newswire. May 23, 2023. 

https://www.prnewswire.com/news-releases/braeburns-brixadi-buprenorphine-extended-release-subcutaneous-injection-ciii-receives-fda-approval-for-moderate-to-severe-opioid-use-disorder-301832521.html 

Office of the Commissioner. FDA approves novel non-opioid treatment for moderate to severe acute pain. U.S. Food and Drug Administration. January 30, 2025. Accessed January 30, 2025.

 https://www.fda.gov/news-events/press-announcements/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain.

Videos

Garadacimab administered via autoinjector/pre-filled pen (AI/PFP) was well-tolerated as a long-term prophylaxis strategy in people with hereditary angioedema (HAE).

These findings, from an ongoing Phase 3 open-label extension study (OLE; NCT04739059) will be presented at the 2025 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress, February 28-March 3, in San Diego, California, by Philip Li, MD, Chief of Rheumatology & Clinical Immunology and Clinical Assistant Professor at The University of Hong Kong.

“Garadacimab (anti-activated factor XII antibody) administered subcutaneously (SC) once-monthly via pre-filled syringe with needle-safety device (PFS/NSD) demonstrated durable protection against HAE attacks with favorable long-term safety/tolerability profiles across clinical studies. Administration via AI/PFP may offer increased convenience. We report efficacy and safety in patients with HAE receiving garadacimab as long-term prophylaxis via AI/PFP from the ongoing Phase 3 OLE,” Li and colleagues wrote.

The OLD included participants in the phase 3 study who received garadacimab 200 mg subcutaneously once a month via PFS/NSD for at least 12 months who transitioned to garadacimab administration via AI/PFP. These data are from post hoc efficacy and safety analyses for garadacimab administration via AI/PFP after transitioning from PFS/NSD through the data cutoff date of July 9, 2024.

The investigators analyzed data from 136 participants who received garadacimab via AI/PFP for a median of 9.4 months (range, 2.7–12.6) for a total exposure of 104.3 patient years). Most participants (95%; n = 129) patients were treated for at least 6 months. Li and colleagues found that the mean monthly attack rate was 0.08 (standard deviation, 0.25).

In terms of safety, 58 (43%) patients experienced at least 1 treatment-emergent adverse event (TEAE), for a total of173 TEAEs. Of these, 6 TEAEs in 3 patients (2%) were related to garadacimab injection-site reactions and were mild in severity. Most TEAEs were mild or moderate (n = 166; 96%), although there were 3 serious AEs unrelated to garadacimab; these were 1 each of food allergy, fractured fingers, and fractured skull. Investigators did not observe any AEs of special interest per protocol (thromboembolic abnormal bleeding events or severe hypersensitivity/anaphylaxis) and no AEs led to death or discontinuation.

Other research on HAE being presented at the AAAAI/WAO Joint Congress found that navenibart seems to reduce patients’ disease burden), as measured by HAE attack frequency, severity, and use of rescue medication.

Primary investigator Joshua Jacobs, MD, Medical Director of Allergy and Asthma Clinical Research, Allergy and Asthma Medical Group, and colleagues found that at the 3-month mark after initiating navenibart treatment, with data from 14 evaluable participants, the baseline monthly rates of 0.95 for mild, 1.25 for moderate, and 0.11 for severe HAE attacks were reduced to 0.13 for mild, 0.05 for moderate, and 0.00 for severe attacks. At the 6-month mark, with data from 7 evaluable participants, baseline monthly rates of 0.45 for mild, 1.54 for moderate, and 0.14 for severe attacks were reduced to 0.10 for mild, 0.08 for moderate, and 0.00 for severe attacks.

The investigators also found that in evaluable participants at 3 months, the mean rate of HAE attacks per month requiring rescue medication were reduced from 1.86 to 0.16 and from 1.32 to 0.10 at 6 months after navenibart treatment. There were no serious treatment emergent adverse events or discontinuations.

Li P, Katelaris C, Reshef A, et al. Efficacy And Safety of Garadacimab Via Autoinjector/Pre-Filled Pen For Hereditary Angioedema Long-Term Prophylaxis – Interim Results From A Phase 3 Open-Label Extension Study. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 638.

Jacobs J, Adatia A, Craig T, et al. Treatment with Navenibart (STAR-0215) Reduces Attack Severity and Use of Rescue Medication in Patients with Hereditary Angioedema (HAE): Interim Results from the ALPHA-STAR Trial. Presented at: 2025 AAAAI/WAO Joint Congress, February 28-March 3. Abstract 196.

Garadacimab, administered via autoinjector/pre-filled pen, has shown to be a well-tolerated long-term prophylaxis for hereditary angioedema (HAE) in a Phase 3 open-label extension study. The study involved 136 participants, with a median treatment duration of 9.4 months, demonstrating a low mean monthly attack rate. Most treatment-emergent adverse events were mild or moderate, with no serious adverse events related to garadacimab. Additionally, navenibart treatment significantly reduced HAE attack frequency and severity, as well as the need for rescue medication, with no serious adverse events reported.

Participants in a phase 3 OLE had a mean monthly attack rate of 0.08.