The FDA greenlit multiple new drugs this month and issued some notable label expansions, including for Eli Lilly’s Kisunla. Meanwhile, the regulator turned away a cell therapy for Duchenne muscular dystrophy and a gene therapy for the rare disease Sanfilippo syndrome.
Amid an exodus of employees—not to mention the official start of Health Secretary Robert F. Kennedy Jr.’s overhaul of the agency—the FDA issued several key verdicts this month.
Among the standout decisions are a Duchenne muscular dystrophy rejection, a dosing modification for an anti-amyloid Alzheimer’s therapy and an approval for the first-ever on-demand oral therapy for hereditary angioedema. Read below for more.
Regeneron’s Bispecific Notches Accelerated Approval for Multiple Myeloma
Drug: Lynozyfic
Decision: New drug approved
Date: July 2
To kick off the month, the FDA handed Regeneron a modest win in multiple myeloma with its approval of linvoseltamab, a bispecific antibody targeting both BCMA and CD3 proteins, for patients with relapsed or refractory multiple myeloma.,
The regulator’s greenlight for the drug, to be marketed as Lynozyfic, was supported by data from the Phase I/II LINKER-MM1 study that demonstrated a 70% objective response rate, including a 45% complete response rate or better. In a prepared statement alongside its announcement of the approval, Regeneron CEO George Yancopoulos said that with this efficacy profile, “Lynozyfic is poised to potentially become a new standard of care for multiple myeloma.”
In a July 2 note, analysts at BMO Capital Markets called the approval a “small win” for Regeneron, with Lynozyfic being a “minor contributor to the company’s broader product portfolio.” BMO models around $600 million in potential revenues for Lynozyfic.
The peak forecast for Lynozyfic is modest in part because it trails Johnson & Johnson’s Tecvayli, which was approved in 2022, giving it a three-year head start.
Regeneron has emphasized the greater convenience of its product, however. According to the pharma, Lynozyfic is the first and so far only bispecific with this mode of action that can be dosed every two weeks, with the possibility of extending to every four weeks if a patient achieves very good partial response or better.
Despite Interference, KalVista Gets Delayed Nod for Only On-Demand HAE Pill
Drug: Ekterly
Decision: New drug approved
Date: July 7
TK weeks after the PDUFA deadline passed, the FDA signed off on KalVista’s sebetralstat, to be marketed under the brand name Ekterly, as the first and only oral on-demand therapy for acute hereditary angioedema (HAE) attacks.
The approval comes after the regulator in June had to push back its decision date for the drug, pointing to “heavy workload and limited resources,” KalVista said at the time. There had also been some internal disagreement over the verdict, with Commissioner Marty Makary reportedly trying to get the application denied, according to Endpoints News, which cited anonymous sources at the agency.
Makary relented after senior staff raised potential legal issues about his interference. The Department of Health and Human Services has denied these claims, with a spokesperson telling Endpoints that they are “totally false and untrue.”
Results of the Phase III KONFIDENT study supported Ekterly’s approval. Results presented in February 2024 showed that both 300-mg and 600-mg doses of Ekterly achieved symptom relief significantly more rapidly, with a median of 1.61 hours and 1.79 hours, respectively, versus 6.72 hours for the placebo group. The open-label KONFIDENT-S trial bolstered these findings, demonstrating that in the real-world setting, Ekterly can help patients address HAE attacks within a median of 10 minutes of onset.
KONFIDENT is the largest HAE program ever conducted, KalVista claims.
PTC Wins Phenylketonuria Nod for Sephience
Drug: Sephience
Decision: New drug approved
Date: July 28
On July 28, the FDA signed off on PTC Therapeutics’ sepiapterin, which will now be marketed under the brand name Sephience, for the treatment of adults and children with phenylketonuria (PKU).
The approval, the biotech noted, grants Sephience a broad label and allows its use for addressing hyperphenylalaninemia in patients 1 month of age and older. This broad labeling, CEO Matthew Klein said in a prepared statement, points to “the potential of Sephience to meet the significant unmet need of PKU patients.”
Data from the Phase III APHENITY trial supported Sephience’s approval. PKU is caused by a deficiency of phenylalanine hydroxylase, leading to the accumulation of phenylalanine in patients’ tissues and body fluids. Results posted in October 2024 showed Sephience could cut phenylalanine by 63% in treated patients. This effect was stronger in study participants with classic PKU, with phenylalanine reduction reaching 69%. Almost 85% of patients achieved phenylalanine levels lower than 360 µmol/L, in line with treatment guidelines.
Lilly, Moderna, Bayer, GSK Win Expanded Labels for Key Assets
July 9: Eli Lilly’s Kisunla
The FDA signed off on a new dosing regimen for Eli Lilly’s Alzheimer’s disease therapy Kisunla. This modified schedule involves a more gradual titration of the drug, which according to the pharma lowers the risk of amyloid-related imaging abnormalities indicative of fluid accumulation (ARIA-E).
Data from the TRAILBLAZER-ALZ 6 study supported this change, showing that at week 24, ARIA-E was detected in 14% of patients treated with the gradual titration of Kisunla, as opposed to 24% of those on the initially approved dosing schedule. By week 52, ARIA-E was reported in 16% and 25% of the respective groups.
July 10: Moderna’s Spikevax
Moderna likewise won a major label expansion this month, with the FDA granting full approval for its COVID-19 vaccine Spikevax in children 6 months through 11 years of age who are at high risk of getting infected. Spikevax was previously available for this age group only under an Emergency Use Authorization.
Spikevax’s full approval comes after two key approvals for Moderna’s mRNA vaccine pipeline last month. The first was for its next-generation COVID-19 shot mNEXSPIKE, which is now cleared for older adults 65 and above, as well as people 12 through 64 years of age who have at least one underlying risk factor. The second was for its respiratory syncytial virus shot, mResvia, which secured broader coverage to include at-risk adults aged 18 through 59 years.
July 14: Bayer’s Kerendia
Also securing a key expansion this month is Bayer’s Kerendia, which the FDA gave a new indication: to reduce the risk of cardiovascular death, hospitalization for heart failure and urgent visits for heart failure in adult heart failure patients with left ventricular ejection fraction of at least 40%.
In the Phase III FINEARTS-HF study, Kerendia elicited a significant 16% reduction in the trial’s primary endpoint, a composite of worsening heart failure events and cardiovascular death. Kerendia likewise resulted in an 18% drop in worsening heart failure events.
Kerendia was first approved in July 2021, indicated to lower the risk of sustained kidney function decline, end-stage kidney disease, cardiovascular death, heart failure hospitalization and non-fatal myocardial infarction in patients with chronic kidney disease associated with type 2 diabetes.
July 17: GSK’s Shingrix
Arguably one of the biggest label expansions this month is for GSK’s shingles shot Shingrix, for which the FDA greenlit a prefilled syringe formulation. This new version, according to the pharma’s press release, simplifies the immunization process for healthcare professionals by removing the need to reconstitute separate vials of the vaccine.
Approved in October 2017, Shingrix is a recombinant herpes zoster vaccine indicated for the prevention of shingles in seniors 50 years and older. The vaccine has also since been expanded to cover at-risk adults 18 years and above. Shingrix is one of GSK’s best-performing assets and has already comfortably passed the blockbuster mark. Last year, the product brought in nearly $4.5 billion in sales.
Capricor Suffers 40% Hit After FDA Thumbs Down DMD Cell Therapy
Drug: Deramiocel
Decision: New cell therapy rejected
Date: July 11
Aside from important approvals, the FDA also issued critical rejections in July, often with harsh consequences on a company’s stock.
One clear example of this is Capricor Therapeutics, which was proposing the investigational cell therapy deramiocel to treat cardiomyopathy in patients with Duchenne muscular dystrophy. The FDA handed Capricor a complete response letter (CRL) on July 11, sending the biotech’s stock freefalling 40% that day.
Capricor has yet to recover. As of writing, the company has dipped some 6.3% further.
The FDA’s rejection was based on Capricor’s data package for deramiocel, which the regulator said fell short of the “statutory requirement for substantial evidence of effectiveness.” The CRL also cited certain deficiencies regarding deramiocel’s chemistry, manufacturing, and controls. Capricor claimed at the time of the rejection that it had already addressed these concerns, but that the FDA was not able to review these submissions “due to the timing of the CRL issuance.”
The rejection came as a surprise to Capricor, CEO Linda Marbán said in a prepared statement at the time. “We have followed their guidance throughout the process,” she said, noting that prior to the CRL the review of deramiocel “had advanced without major issues, including a pre-licensure inspection and completion of the mid-cycle review.”
As in the case of KalVista’s Ekterly, deramiocel has been the subject of some internal disagreement at the FDA. Nicole Verdun, the former top regulator of cell and gene therapies at the FDA’s Center for Biologics Evaluation and Research (CBER), had previously scheduled an advisory committee meeting for the application, which new CBER leader Vinay Prasad later cancelled. Verdun was subsequently pushed out of the agency.
Ultragenyx Misses Out on Rare Genetic Disease Approval
Drug: UX111
Decision: New gene therapy rejected
Date: July 11
Ultragenyx reported on July 11 that the FDA had declined to approve UX111, its gene therapy for Sanfilippo syndrome type A, a rare and genetic metabolic disorder that manifests as a broad range of symptoms, including developmental delays and progressive intellectual disability.
According to the biotech, the rejection was not linked to its data package for UX111. “The FDA has acknowledged that the neurodevelopmental outcome data provided to date are robust and the biomarker data provide additional supportive evidence,” a statement from Ultragenyx read.
Instead, the CRL cited manufacturing issues that were “not directly related to the quality of the product,” Ultragenyx said. “The company believes that these observations are readily addressable.”
Ultragenyx added that the company will work to resolve these issues “in the next few months,” building up to a resubmission for UX111. The rare disease biotech expects to undergo another six-month review period after refiling for approval.
The rejection capped off a difficult week for Ultragenyx, which on July 9 reported that its Phase II/III osteogenesis imperfecta study for the anti-sclerostin antibody UX143 would be moving to its final analysis. William Blair analysts at the time took this to mean that the trial failed to meet an efficacy threshold that would have otherwise warranted its early termination.
As of writing, Ultragenyx’s shares have slid 33% since the osteogenesis imperfect announcement.
Roche’s Earlier-Stage Push for Columvi Falls Short
Drug: UX111
Decision: Label expansion rejected
Date: July 21
The FDA has rejected Roche and subsidiary Genentech’s proposal to use the bispecific antibody Columvi as part of a second-line treatment regimen in patients with diffuse large B cell lymphoma. The Complete Response Letter cited insufficient evidence to support the use of Columvi in this indication in the U.S. patient population.
Roche used data from the Phase III STARGLO study to support its application. Results showed that patients treated with the Columvi combo saw a 41% drop in the risk of death compared with those who received rituximab, gemcitabine and oxaliplatin. The Columvi-based regimen likewise hit secondary endpoints, including progression-free survival.
Despite these results, the FDA’s Oncologic Drugs Advisory Committee (ODAC) in May voted 8–1 against Columvi’s expansion, raising concerns about the applicability of the drug’s efficacy data in the U.S. In STARGLO’s intention-to-treat population, only 25 of more than 270 participants were from North America.
Columvi remains approved as a third-line treatment option for diffuse large B cell lymphoma (DLBCL) under the FDA’s accelerated pathway program. Roche and Genentech are also studying Columvi in the Phase III SKYGLO study, which combines the bispecific with Polivy, Rituxan, cyclophosphamide, doxorubicin and prednisone for the treatment of patients with large B cell lymphoma.
The companies are in discussions with the FDA to use SKYGLO as the new postmarketing requirement to convert the third-line DLBCL indication to a full approval, as per their July 21 announcement.
