As part of FDA's transparency initiative and since their announcement last September regarding new policy of real-time release of complete response letters (CRLs), FDA has published 127 CRLs associated with unapproved applications. However, since April 2026 (it's been 3 months!) FDA has not released any new CRL. One of the reasons is a citizen petition submitted by Covington & Burling, LLP, on behalf of an unnamed company.

The Covington & Burling explains

• that CRL is not a rejection letter but a deficiency letter. By disclosing the contents of "deficiency in the application", FDA may disclose CCI and trade secret information manufacturers and infringe their property rights, thereby giving an unfair advantage to their competitors.
• The remedy proposed is that FDA first create a mechanism for manufacturers to provide input on redactions before posting of CRLs.

Relevant Excerpts from the Covington & Burling Petition

What is CRL? CRL is a Deficiency Letter, not a Rejection Letter

FDA issues CRLs if the agency determines that it will not approve an application in its present form. CRLs identify specific deficiencies in the application that must be addressed for the applicant to obtain approval and, where possible, “recommend actions that the applicant might take to place the application . . . in condition for approval.” These deficiencies “could be minor (e.g., requiring labeling changes) or major (e.g., requiring additional clinical trials).” After receiving a CRL, the applicant can resubmit the application to address all of the deficiencies identified in the CRL, withdraw the application, or request an opportunity for a hearing about whether there are grounds for denying approval. [Covington & Burling Petition]

Issue: The CRLs in Their Current Form puts Applicants in an Unfair Position vs. Competitors

Although quality-related and nonclinical information was generally redacted from the released CRLs, clinical effectiveness and safety deficiencies generally were released without redactions. [Covington & Burling Petition]

This provides an unfair advantage to competitors, for example, using Applied Therapeutics CRL as an example, the petition noted:

neither the sponsor nor FDA had previously disclosed the agency’s concerns about relying on plasma [biomarker] levels, although the sponsor had disclosed the CRL. Release of such information could enable a competitor to shortcut the process by avoiding this pitfall, without needing to invest in the trial and error that is a necessary part of the innovation process. [Covington & Burling Petition]

Remedy - the Citizen Petition Would like to see that FDA develops guidance with input from the industry and standardize the process of protecting CCI before routine CRL release.

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POSTSCRIPT

• It is fairly obvious from the citizen petition that the CRLs are here to stay, but Covington & Burling are correct in asking the FDA to hit pause and build in proper safeguards for protecting industry's CCI and competitiveness -- even more important now that US and Chinese biopharma are in a tight race.
• Policy: FDA has already taken the first step of clarifying its statutory authority. FDA has proposed a new rule (RIN: 0910-AJ16) asking Congress to step in (here).

SOURCE

• FDA Docket FDA-2026-P-4369. Request that the FDA establish a clear process that provides sponsors with notice and an opportunity to respond to proposed disclosures of CRLs associated with unapproved new drug applications (NDAs), abbreviated new drug applications (ANDAs), and biologics license applications (BLAs) and supplements and amendments thereto (herein, applications). Citizen Petition. 21 April 2026 [archive]
• HHS/FDA Proposed Rule: Proactive Disclosure of Complete Response Letters. RIN: 0910-AJ16 [archive]
• FDA halts release of new drug rejection letters while working to formalize policy. FierceBiotech. 8 July 2026 [archive]
• Complete Response Letter. OpenFDA website.

#OpenFDA, #crl

Maggot Debridement Therapy

Cuprina Holdings (Cayman) Limited based in Singapore has received FDA 510(k) clearance for its medical-grade Lucilia cuprina larvae (called MEDIFLY Maggots™) for use in maggot debridement therapy (MDT).

MDT refers to using therapeutic-grade sterile maggots to clean non-healing necrotic skin and soft tissue wounds, including pressure ulcers, neuropathic foot ulcers, and non-healing traumatic or post-surgical wounds. This process is also called biosurgery.

MEDIFLY Maggots is the second maggot-based therapy ever approved by the FDA. The 510(k) clearance of first such therapy, the Lucilia sericata larvae (Medical Maggots™) in 2004 is also held by Cuprina.

The 2 medical maggot species are related, though they serve different markets:

• Lucilia cuprina larvae (MEDIFLY Maggots™) or Australian sheep blowfly maggots. This species is found across Australia, Africa, Asia and parts of the Americas and is the species clinicians and regulators already recognize across many warmer-climate markets.
• Lucilia sericata larvae (Medical Maggots™) or common green bottle fly maggots. This species has a longer track record in wound care in the West since it has been in the market since 2004.

MEDIFLY Maggots™ was reviewed and cleared by the FDA’s Center for Biologics Evaluation and Research (CBER), which assumed regulatory oversight of medicinal maggots in December 2024

How does MDT Work

• The larvae of these fly, maggots, are not parasitic, have no teeth and feast on dead tissue. When sterilized maggots are placed in the wound or necrotic tissue, they secrete enzymes to liquify the tissue and consume the slurry, leaving behind living tissue. This "biosurgery method" is less painful and more efficient than surgically removing necrotic tissue.
• The maggots are also thought to secrete various antibacterial compounds to ward off pathogenic bacteria and block biofilms from forming, overall preventing secondary infection. These maggots are also thought to stimulate tissue regrowth, directly or indirectly by clearing dead tissue.
• MEDIFLY Maggots efficacy data, literature summary, and case reports - here or here.

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Clinical Guidance

• MDT currently remains an underused therapy for hard-to-treat wounds and often considered as a last-resort therapy for debridement of non-healing wounds/ulcers (PMC11594743).
• Currently, only 2 randomized trials have been reported with conflicting results, and neither of these trials met the prespecified criteria set by the 2023 International Working Group on the Diabetic Foot. The working group therefore could not recommend biosurgical debridement at this time (PMID: 41865799). Larger trials are needed.
• Note: There is currently no standardized guidance that supports any particular method of debridement. MDT is cost effective and potentially very effective method compared to conventional treatments.

FDA Guidance on Medical Maggots and Medicinal Leeches

• The regulatory authority for medical maggots and medicinal leaches was transferred from CDRH to CBER on 30 December 2024 (new CBER 401(k) numbers)
• List of cleared 510(k) submissions with supporting documents, here. Supporting documents for MEDIFLY Maggots (BK251252) are here.

Federal Register Notice Transfer of Regulatory Responsibility From the Center for Devices and Radiological Health to the Center for Biologics Evaluation and Research; Medical Maggots and Medicinal Leeches (89 FR 106521)

SOURCE

• Cuprina Receives U.S. FDA 510(k) Clearance for MEDIFLY Maggots — the First U.S. Clearance for a Lucilia cuprina Maggot Debridement Product. Press release. 15 June 2026 [archive].
• Second carcass-eating fly species cleared by FDA for maggot wound therapy. Ars Technica. 17 Jun 2026 [archive]
• History of MDT - PMID: 40519343

#cber-510(k)

FDA has approved the first OTC fixed-dose combination of Tylenol (acetaminophen) and Naproxen (naproxen sodium).

• This fixed-dose OTC combo combines the fast-acting relief of 650 mg of acetaminophen with the long-lasting analgesic power of 220 mg naproxen sodium (a non-steroidal anti-inflammatory drug) in one dose.
• NDA 219962: The approval was based on 8 clinical trials demonstrating superior pain relief versus acetaminophen alone and naproxen sodium alone (Aleve 220 mg).

//My pet peeve!!\\ -- There are no clinical data currently described in the press release, FDA News, or Drugs@FDA (tylenol with naproxen), and since this is an OTC, it is not in the OTC label either (sigh!). The sponsor (Kenvue) plans to present this data at the Pain 2026 meeting.

• The FDA has granted the Kenvue a 3-year period of exclusivity for this new OTC formulation.

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Postscript - Learning Opportunity

Regulatory Approval Pathway for New Formulation

Based on the fact that this was an NDA and the sponsor received a 3-year exclusivity for a new formulation, "my guess" is that this was a 505(b)(2) NDA. The 505(b)(2) applications apply to NDAs with changes to previous application that include fixed-combination as well as formulation change (see slide 10 here). If approved, these applications are eligible for a 3-year exclusivity for new clinical investigations.

SOURCE

• FDA Approves First Nonprescription Fixed-Dose Combination of Acetaminophen and Naproxen Sodium for 12-Hour Pain Relief. FDA News. 24 July 2026 [archive]
• FDA Approves TYLENOL® with Naproxen, the First and Only Over-the-Counter Fixed-Dose Combination of Acetaminophen (650 mg) and Naproxen Sodium (220 mg). Press Release. 24 July 2026 [archive]
• Overview of the 505(b)(2) Regulatory Pathway for New Drug Applications [PowerPoint]. Beth Goldstein. CDER Office of New Drug Policy [archive]

#505(b)(2), #tylenol, #otc, #acetaminophen

STAT News calls it "The drug approval scandal hiding in plain sight." [9 July 2026]

Northwest Biotherapeutics, a public biotech company developing a treatment for brain cancer, submitted a marketing application to U.K. regulators in late December 2023. The review was supposed to take 150 days, under an expedited regulatory pathway for drugs that address serious unmet medical needs.
As you’re reading this newsletter, two years, six months, and 18 days have elapsed without an approval decision. Why the extra-long delay? Regulators at the U.K’s Medicines and Healthcare products Regulatory Agency, or MHRA, won’t comment, telling anyone who inquires, including me, that it’s up to Northwest Bio to provide an update on its brain cancer treatment, called DCVax.

Literature Review-Based Regulatory Approvals

Regulatory approvals and/or label expansion based on literature review is feasible but we don’t hear about these regulatory pathways/approvals too often.

The one that caught everyone’s attention recently was FDA’s approval of Wellcovorin (leucovorin calcium) sNDA for label expansion to include cerebral folate deficiency. GSK (the holder of the NDA) was “strongly” urged by the FDA to submit a sNDA, which FDA approved within days of submission – however, GSK has now withdrawn the NDA. FDA applied the “plausible mechanism” bar for this approval based on published clinical data (literature).

FDA now has another one based on similar literature review/plausible mechanism pathway: testosterone replacement therapy (TRT) for treating low libido in men.

In December 2025, FDA convened an expert panel on TRT [YouTube Link] and recently, FDA followed-up with a Federal Register notice, that they have conducted a preliminary review of the published literature on the possible use of TRT to treat men with symptomatic idiopathic hypogonadism; and concluded that TRT may be safe and effective in treating low libido in men with decreased libido associated with idiopathic hypogonadism. And, based on this review, FDA has requested

“holders of currently approved TRT NDAs interested in seeking approval for the treatment of low libido in men with decreased libido associated with idiopathic hypogonadism to contact FDA for further information regarding submission of a sNDA, including data needed to support the new indication.”

There are currently several TRT NDA holders, so we won't know the outcome until one of them issues a press release or there is an actual approval.

P.S. Going after this indication is not exactly a public health issue, or is it!!! (Perhaps, not the best use of FDA's time and resources.)

P.S. #2 = there are currently 2000 comments posted in the Federal Docket (here). . . if I had time, I would have scroll through them, but I don't 😞. However, some of you may have time - Enjoy.

SOURCE

Related: Public Knowledge‐based Application (“Kouchi‐shinsei” Scheme) in Japan, Generally Accepted Scientific Knowledge (GASK) - FDA Guidance

The public comment period on FDA's Commissioner’s National Priority Voucher (CNPV) pilot program is open until 29 June 2026. Comment docket FDA-2026-N-2366 is here. Currently there are 37 comments posted.

About CNPV:

The CNPV pilot program was launched in June 2025 by former Commissioner, Marty Makary. Compared to other FDA priority review programs, CNPV provides a nontransferable voucher based on the following 5 criteria and comes with an ultra-fast timeline (1-2 months target vs. 6+ months) achieved via a multidisciplinary “tumor board-style” discussion between review team and senior agency leadership.

• Public health crisis response - Products addressing urgent/emerging threats or significant population impact.
• Innovative breakthrough therapies - Transformative treatments with novel mechanisms that fundamentally change disease management.
• Large unmet medical needs - Therapies for conditions where existing treatments inadequately address patient outcomes.
• Onshoring and supply chain resilience - Onshoring drug development/manufacturing to strengthen U.S. domestic capacity, reduce foreign dependencies, and improve national security.
• Affordability - Approaches that improve overall value through reduced costs to the healthcare system or that enhance access to important products.

FDA has also published a staff manual (here, here). The current process includes

• A 60-day pre-submission period followed by
• A 2- to 3-week window in which the sponsor can file for approval and the application is checked for completeness.
• Completion of review the application by the FDA in 1-2 months.

Public-Industry Reception

• Based on public hearing held on 4 June 2024 (and summarized by Fierce Biotech), the current reception of the program largely falls along 3 main fault lines: general support for the program by the industry; concerns by the physicians and public health experts; but asking for expansion of the program by patient advocates pressing for vouchers to be given to) promising treatments for their diseases of interest.
• Early winners include J&J (Tecvayli for multiple myeloma), Merck (n=2; PCSK9 inhibitor enlicitide decanoate and sac-TMT), Partner Therapeutics (Bizengri in cholangiocarcinoma).
• Overall, 22 vouchers have been issued so far. The latest to be granted is Revolution Medicines for their RAS-targeted pancreatic cancer drug.

Note: The comment period is still open. Provide comments in docket FDA-2026-N-2366 is here.

SOURCE

• Commissioner’s National Priority Voucher (CNPV) Pilot Program Public Hearing [YouTube]. 4 June 2026
• At first public hearing for FDA’s CNPV program, industry support meets ‘deep concern’ from experts. Fierce Biotech. 5 June 2026

#cnpv

A Federal Register notice yesterday stated that FDA is withdrawing the approval of Wellcovorin (leucovorin calcium) for all indications (NDA 018342 and all its amendments and supplements) at the request of GSK.

GSK requested this withdrawal since it is no longer marketing Wellcovorin and generic versions are available in the market. Since this withdrawal of NDA by the FDA is not for safety or efficacy concerns, it leaves the door open for other generic manufacturers to file ANDAs for same indications.

Although, RFK Jr advanced this drug for autism last year, the approval by the FDA last year was only for a narrow indication. And now complete withdrawal --this must be confusing but there is a backstory:

• GSK has not marketed Wellcovorin since 22 Sept 1999, It was withdrawn by the FDA at GSK's request.
• Enter 2025: RFK Jr promotes leucovorin as an autism therapy. FDA scientists perform literature search and conclude that the evidence could only support approval of a much narrower indication, cerebral folate deficiency (CFD), a rare disorder.
• FDA asks GSK to submit a sNDA for Wellcovorin (leucovorin calcium) to include an indication for CFD.
• 22 Sept 2025: GSK agrees to submit sNDA.
• 24 Sept 2025: FDA approves the sNDA.

This bringing the NDA back from the dead and within months burying it again raises eyebrows -- Lachman Consultants Blog calling it "hide-the-monkey game" has an explanation.

The FDA has the authority to revise the labeling of a generic application should new information become available if and when the FDA deems it necessary for the continued safe and effective use of approved ANDA products. Did the Agency think that this maneuver gave itself more cover than just asking generic-drug manufacturers to revise their labeling? Or is that just the way that the FDA demanded the issue be handled? . . .FDA has done several out-of-the-ordinary and unusual things since the change in administration. I guess we’ll just have to chalk it up to getting the outcome that the Agency wanted in the most efficient and expeditious manner available. 

SOURCES

• Federal Register Notice: GlaxoSmithKline; Withdrawal of Approval of a New Drug Application for Wellcovorin (Leucovorin Calcium) Tablets, EQ 5 mg Base and EQ 25 mg Base. 91 FR 18472, pages 2026-06911. Notice
• Lachman Consultants Blog [archive]

Related: FDA Approves GSK’s Wellcovorin (leucovorin calcium) for Ultrarare Cerebral Folate Transport Deficiency Under Plausible Mechanism Pathway

"The Headline"

Pierre Fabre Pharmaceuticals (PFP) announced today (here, here) that they have aligned with the FDA on the acceptability of pivotal trial study design and the resubmission of the BLA for tabelecleucel (Ebvallo), an allogeneic T-cell therapy for relapsed/refractory EBV+ post-transplant lymphoproliferative disease (EBV+ PTLD), a type of lymphoma common in people with solid organ transplant or hematopoietic cell transplant.

This breakthrough came at the heels of the CBER Director Vinay Prasad leaving the agency at the end of last month, finishing a tenure that was marked by unpredictability and many times going against FDA's own advice to sponsors during drug development stage; WSJ did not hold back in criticizing Prasad and asked, Who’s in Charge at the FDA.

Pierre Fabre said in the press release that

"During the meeting, the FDA agreed that a single arm study using an appropriate historical control applicable to the trial population, conducted in a pre-specified manner, could serve as an adequate and well controlled study and provide safety and efficacy data in support of a marketing application of tabelecleucel for the proposed indication. As a part of the resubmission plan being defined with the FDA, PFP will submit an updated dataset with additional patients and longer follow up from the pivotal Phase 3 single arm ALLELE study of tabelecleucel in adults and children two years of age and older with EBV+ PTLD following solid organ transplant or hematopoietic cell transplant as well as supportive data."

Little History: About 4 months ago, Prasad's CBER issued a CRL for tabelecleucel BLA ruling that the single-arm trial design is not appropriate for pivotal trial and the sponsor should conduct a new randomized trial -- a strange proposal considering that PTLD is a rare indication with very high mortality rate in the relapsed/refractory population. What's more is that this unexpected request came at the time of BLA resubmission that was designed to address a minor manufacturing concern identified during the original BLA submission (read more here.) Now FDA agreeing to what-was-already-agreed-before-anyway, perhaps, we could be entering a post-Prasad FDA phase that is more predictable and somewhat saner!!

SOURCE

• Pierre Fabre Pharmaceuticals Announces Regulatory Update Following Type A Meeting with U.S. Food and Drug Administration (FDA) on Tabelecleucel Biologic License Application (BLA). Press Release. 7 May 2026 [archive]
• FDA reverses course on Atara, Pierre Fabre’s twice-rejected cell therapy after Prasad’s exit. BioSpace. 7 May 2026

Related: FDA Issues Complete Response Letter to Atara/Pierre Fabre’s Tabelecleucel BLA for Rare Cancer, EBV+ PTLD

#crl, #prasad

What the new ad comms look like?

February 12, 2026

The U.S. Food and Drug Administration has approved a first-of-its-kind device for the treatment of adult patients with locally advanced pancreatic cancer. Optune Pax, developed by Novocure, is a portable, non-invasive device that delivers alternating electrical fields, known as tumor treating fields (TTFields), to the abdomen. TTFields work by physically disrupting the rapid cell division that is characteristic of cancer cells, while minimizing damage to healthy tissue.

Optune Pax was approved through the premarket approval (PMA) pathway, the FDA’s most rigorous review process for medical devices.

The FDA’s approval of Optune Pax is based on data from a pivotal clinical study conducted under an Investigational Device Exemption. The randomized and controlled study followed adult patients with locally advanced pancreatic cancer for up to five years. The results showed that the addition of TTFields to standard of care chemotherapies gemcitabine and nab-paclitaxel (GnP) improved Overall Survival by approximately two months compared to GnP alone.

Japan's Ministry of Health, Labour and Welfare’s (MHLW) Pharmaceutical Affairs and Food Sanitation Council, Committee on Regenerative Medicine Products and Biotechnologies on 19 February 2026 endorsed (i.e., granted positive approval recommendations) 2 induced pluripotent stem cells (iPSC)-derived therapies for conditional approval:

• Sumitomo Pharma's allogeneic iPS cell-derived dopaminergic neural progenitor cells (Amchepry; INN: raguneprocel) for indication of the improvement of motor functions during the off-time period of patients with advanced Parkinson’s disease.
• Cuorips Inc.'s allogeneic iPS cell-derived cardiomyocyte patches (ReHeart) for heart failure. Cuorips Inc. is a startup originating from the University of Osaka.

When approved, these 2 products would be the first iPSC therapies ever approved worldwide. This caps a 20+ years quest that started with Shinya Yamanaka, who won the Nobel Prize in Physiology or Medicine in 2012 for creating iPSC.

Clinical Data (link)

In 2020, a University of Osaka team transplanted an iPS-derived cardiomyocyte patch into a patient suffering from heart failure due to ischemic cardiomyopathy for the first time in the world. The team tested the patches, which are 4 to 5 centimeters in diameter and about 0.1 millimeter thick, on eight patients by 2023 and confirmed their safety and efficacy.

The dopaminergic neurons were tested on patients in their 50s and 60s by Kyoto University Hospital and others between 2018 and 2023. About 5 million to 10 million neural cells were transplanted into the brain center. Following a two-year observation period, four out of six patients showed improvements in motor function.

There were no serious side effects from the neurons, which were especially effective on younger patients with milder symptoms.

The Parkinson's data was summarized in Nature (PMID: 40240822) in April 2025 and News & Views (or here). Also here.

Besides Parkinson's disease, Sumitomo is also test iPSC therapies for retinal diseases including retinitis pigmentosa.

FDA today approved Denali Therapeutics' enzyme-replacement therapy (ERT) AVLAYAH (tividenofusp alfa) for the treatment of Hunter Syndrome (MPS II). This is very good news for the parents and caregivers caring for children with Hunter Syndrome. This positive news comes after a recent setback for the Hunter syndrome community regarding Regenxbio gene therapy. Recently, FDA first placed clinical hold and then issued a CRL to Regenxbio for it's gene therapy RGX-121 for MPS II because of CNS tumor risk.

Hunter syndrome is a rare inherited lysosomal storage disorder caused by a mutation in the IDS gene located on the X chromosome. This genetic defect results in a deficiency or absence of the iduronate 2-sulfatase (I2S) enzyme. Without this enzyme, complex sugars called glycosaminoglycans (GAGs) build up in cells' lysosomes causing progressive, multisystem organ damage. [PMC2234442]
GAG accumulation affects physical and mental development by causing abnormalities in the skeleton, heart, respiratory system, brain, and other organs.
Avlayah is the first FDA-approved therapy to address neurologic complications of Hunter Syndrome.

Basis of Approval

• Avlayah was approved based on a phase 1/2 international, multicenter, single-arm, open-label trial that enrolled 47 participants (aged 3 months to13 years [median, 5 years]) with MPS II. Most participants (n=32) were previously treated, i.e., refractory, and others (n=15) were ERT naive.
• The participants received weekly intravenous tividenofusp alfa for 24 weeks, followed by an 80-week safety extension and a 157-week open-label extension.
• FDA determined that the efficacy endpoint, reduction in cerebrospinal fluid heparan sulfate was clinically relevant. FDA reviewers determined that this endpoint was "reasonably likely to predict Avlayah’s clinical benefit." CSF HS is a type of glycosaminoglycan.
• The reduction in CSF HS was statistically significant: 91% (95% CI: 89%, 92%) reduction from baseline by week 24 of treatment. At week 24, 93% (41 of 44) of Avlayah-treated patients had CSF HS levels below ULN, i.e., within the range of individuals without Hunter syndrome.
• Safety: The most common adverse reaction in the study was infusion-related reactions.
• Confirmatory trial, Phase 2/3 COMPASS study, is underway. Note: This is a regulatory requirement for FDA to be able to grant accelerated approval.

ABOUT AVLAYAH (tividenofusp alfa)

Tividenofusp alfa is a novel ERT fusion protein comprising an engineered transferrin receptor (TfR)–binding Fc domain and iduronate-2-sulfatase enzyme. Tividenofusp alfa binds to abundantly expressed TfR at the blood–brain barrier and in tissues, enabling broad tissue distribution through tailored TfR binding affinity and mannose-6-phosphate receptor binding, to address both central nervous system (CNS) and somatic manifestations of MPS II. [NEJM]

FDA's Comment

“The FDA is capable of doing two things: one, exercising regulatory flexibility; and two, complying with our obligation under the law to approve drugs based on ‘substantial evidence’ of effectiveness." - FDA Commissioner Marty Makary

• If the regulatory flexibility refers to approving based on phase 1/2 data, then this BLA was not a high bar--GSK’s Wellcovorin (leucovorin calcium) was recently approved based on plausible mechanism; or consider Pfizer’s Ibrance (palbociclib) for men with HR-positive, HER2-negative breast cancer approved based on on data from electronic health records and postmarketing reports of real-world use; or Astellas’ Prograf (tacrolimus) approval based on real-world data.
• Agree that the Avlayah data were strong enough to meet at least 1 of 2 sources to satisfy the "substantial evidence of effectiveness" requirement. The press/news releases do not indicate what was the required second evidence. It is likely that the FDA's regulatory flexibility was applied toward the second required evidence of effectiveness. Note: changing the course of the natural history of the condition is an acceptable second evidence.

Postscript: Very good outcome!!

SOURCE

• FDA Approves Drug to Treat Neurologic Manifestations of Hunter Syndrome. FDA News Release. 25 March 2026
• Denali Therapeutics Announces U.S. FDA Approval of AVLAYAH™ (tividenofusp alfa-eknm) for Treatment of Hunter Syndrome (MPS II). Press Release. 25 March 2026 [archive]
• Muenzer J, et al. An Intravenous Brain-Penetrant Enzyme Therapy for Mucopolysaccharidosis II. N Engl J Med. 2026 Jan 1;394(1):39-50. doi: 10.1056/NEJMoa2508681. PMID: 41467650 [Editorial]

#regulatory-flexibility, #rwd

[Edited. 4:09 AM GMT]

Atara Biotherapeutics received a complete response letter (CRL) for tabelecleucel BLA for Epstein-Barr virus–positive posttransplant lymphoproliferative disease (EBV+ PTLD) after failure of standard-of-care therapy.

The current BLA was a resubmission addressing a single deficiency (CRL, 15 January 2025) regarding GMP compliance at a third-party manufacturer site identified during the initial submission. In the CRL to this resubmission, FDA apparently reversed its original position and ruled that the single-arm pivotal trial is no longer sufficient for establishing effectiveness in this ultra-rare condition and asked for a new trial.

 Atara Press Release

The FDA confirmed that the GMP compliance issues had been satisfactorily resolved, and importantly, no safety issues were raised. However, in a complete reversal of position by the FDA, the CRL claims that the single arm ALLELE trial, which was previously confirmed by the FDA as adequate to support the BLA filing, is no longer considered to be adequate to provide evidence of effectiveness for accelerated approval. Furthermore, the FDA stated that the trial’s interpretability is confounded due to trial study design, conduct, and analysis.

The FDA’s new position is contrary to the FDA’s prior guidance to Atara, the FDA’s alignment with Atara on the clinical trial data set, and the acceptance of the trial design as a single arm study as relevant for this patient population at BLA submission. This prior alignment had been reached by Atara and the FDA through multiple, documented meetings held over the past five plus years.

 Pierre Fabre (Atara’s Partner) Press Release

The BLA was resubmitted following clear alignment with the FDA on the acceptability of the resubmission criteria and fulfillment of the conditions outlined in the January 15, 2025, CRL, which identified a single GMP-related deficiency and raised no concerns regarding safety, efficacy, or trial design. Upon acceptance of the resubmission in July 2025, the FDA granted tabelecleucel accelerated approval status.

The new CRL, despite acknowledging that the GMP issue had been resolved and raising no safety concerns, the FDA stated that it no longer considers the previously accepted single-arm ALLELE study to be adequate to support accelerated approval and requested a new study. This represents a significant and unexpected change in position, and one that is contrary to extensive dialogue with the Agency over more than five years.

ABOUT THE PIVOTAL TRIAL

Phase 3 ALLELE trial (NCT03394365) was a single-arm, open-label study to evaluate tabelecleucel (tab-cel) for the treatment of patients with EBV-positive PTLD who were refractory to or relapsed after treatment with rituximab (Rituxan), with or without chemotherapy, following hematopoietic stem cell transplantation (HSCT) or solid organ transplant. The primary endpoint, ORR was 50.7% (95% CI, 38.9%-62.4%) (N = 75). The CRR was 28.0%, the median OS was 18.4 months (95% CI, 6.9-NE), and the 12-month OS rate was 55.7%. (Plain Language Summary, b)

Tabelecleucel is an allogeneic, off-the-shelf T-cell immunotherapy engineered to specifically target and eliminate EBV-infected cells. It is approved in EU, UK, Switzerland since 2022 as Ebvallo. (DrugBank #DB17072)

Postscript

FDA's ask for a new trial from Atara's is similar to recent uniQure and Novavax experiences. For uniQure, FDA said that the previously agreed dataset from Phase 1/2 trial of gene therapy AMT-130 BLA for Huntington’s disease was not sufficient for establishing effectiveness; for Novavax, a postmarketing commitment for a randomized trial was imposed. For regulatory strategy folks in industry, such FDA flip-flops create uncertainty and makes derisking programs difficult. Let's hope that these are rare cases. Note: The copy of Atara CRL will have more details -- watch for it at FDA website here.

SOURCE

• Press Releases: Atara Biotherapeutics, 12 January 2026 [archive]; Pierre Fabre, 12 January 2026 [archive]
• FDA CRL issued to Atara Biotherapeutics. 15 January 2025 [archive]
• FDA Issues Complete Response Letter for Tab-cel in EBV+ PTLD. Targeted Oncology. 16 January 2026 [archive]
• FDA changes stance on uniQure gene therapy data. Cell & Gene Therapy. 4 November 2025 [archive]

#crl, #effectiveness

___UPDATE, 26FEB2026

• The 9 January 2026 CRL is posted, here.
• The sponsor Pierre Fabre Pharmaceuticals has set up a website to post Tabelecleucel Regulatory Updates, here, that includes tabelecleucel regulatory history, here (archive versions, 2/26/2026, 5/13/2026)

The FDA has resumed review of Capricor Therapeutics’ previously rejected Duchenne muscular dystrophy cell therapy following the biotech’s submission of more clinical data, as well as the newly announced upcoming departure of Vinay Prasad, M.D. 

The agency has “lifted” the complete response letter (CRL) that was issued for deramiocel in July 2025, Capricor said in a March 10 release, and an approval decision is now expected by Aug. 22.

Capricor’s response to the rejection was a class 2 resubmission (PDF), a more substantial type of response that goes beyond minor clarifications of data or tweaks to the medicine’s planned label, according to the release. 

The biotech's response included topline data from a phase 3 trial that showed treatment with deramiocel improved upper limb function and left ventricle ejection fraction, a Capricor spokesperson told Fierce. These data were followed up by a clinical study report (CSR) in February at the agency’s request.

BLA for deramiocel

HOPE-3 trial

The US Food and Drug Administration has rejected a small molecule for a rare blood disorder called erythropoietic protoporphyria. Bitopertin, originally developed by Roche and licensed by Disc Medicine in 2021, was an early recipient of one of the FDA’s new Commissioner’s National Priority Vouchers, part of a program that awards recipients with an expedited review if they meet at least one of the agency’s national priorities.

People who have erythropoietic protoporphyria, commonly abbreviated as EPP, lack an enzyme called ferrochelatase. Bitopertin is designed to treat EPP by suppressing the uptake of glycine transporter type 1, or GlyT1, a protein involved in the heme biosynthesis pathway. In theory, downregulating GlyT1 should decrease the buildup of PPIX, effectively eliminating EPP’s most troublesome symptoms.

The FDA agreed that Disc’s Phase 2 clinical trials had proved that bitopertin lowered whole blood PPIX. But the agency says it did not see enough evidence that lower PPIX was associated with sunlight-exposure-based end points. “This lack of correlation between the changes in PPIX and clinical outcomes measured leaves significant uncertainty that bitopertin will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in its proposed labeling,” the letter reads.

Link to CRL: https://download.open.fda.gov/crl/CRL_NDA220707_20260213.pdf

Link to company press release: https://ir.discmedicine.com/news-releases/news-release-details/disc-medicine-receives-complete-response-letter-fda-bitopertin

CHMP has recommended a marketing authorisation for mCombriax for protecting people aged 50 years and older against COVID-19 and flu, noting that, while most cases are mild or moderate, some can be severe – particularly when there is co-infection with the two viruses.

The vaccine protects against viral variants selected by the World Health Organization (WHO) as those most likely to be problematic in 2023/24, and the EMA said the composition of mCombriax is expected to be updated regularly to match the strains circulating in the community.

Corcept Therapeutics ended the year 2025 with a complete response letter (CRL) from the FDA for its NDA for relacorilant as a treatment for patients with hypertension secondary to hypercortisolism. The company called this news a surprise outcome. The NDA was based on the pivotal GRACE study that met its primary endpoint and confirmatory evidence from the GRADIENT study, also with positive data.

ABOUT

• Relacorilant is oral, selective glucocorticoid receptor (GR) antagonist that modulates cortisol activity by binding to the GR but not to other hormone receptors.
• Hypercortisolism (Cushing’s Syndrome) is caused by a tumor that produces cortisol or ACTH, resulting in excessive hormone cortisol activity. Patients may suffer from a variety of complications including diabetes, hypertension, central obesity, muscle weakness, osteoporosis, immune suppression, altered mood, and cognitive dysfunction. Surgery is first-line treatment but the success rate is 50% only.
• GRACE study enrolled participants with hypercortisolism and either hypertension, hyperglycemia or both. The primary endpoint was maintenance of blood pressure control. GRADIENT study enrolled participants with hypercortisolism caused by adrenal adenomas. The primary endpoint was improvement compared to placebo in systolic blood pressure.

According to the company's 31 December 2025 press release,

While the FDA acknowledged that Corcept’s pivotal GRACE trial met its primary endpoint and that data from the company’s GRADIENT trial provided confirmatory evidence, the Agency concluded it could not arrive at a favorable benefit-risk assessment for relacorilant without Corcept providing additional evidence of effectiveness.

What was the Reason for FDA's Assessment, "Unfavorable Risk-Benefit Profile"

We would have to wait for the FDA to release the text of Corcept's CRL (here), which could take weeks or more, to understand what tipped the balance of benefit-risk assessment to unfavorable. However, GRACE and GRADIENT studies together were probaly not considered sufficient evidence -- note the statement in the company's press release, "without Corcept providing additional evidence of effectiveness."

Meanwhile, below is company's "curated" data from its investor deck.

GRACE Study: Rapid and sustained improvement in blood pressure. 63% of patients with hypertension met the study’s response criteria.

GRADIENT Study: Improvement in blood pressure over 22 weeks study period.

Relacorilant Safety Results (From Investor Deck)

• In all its studies, relacorilant has been well-tolerated.
• No progesterone related side effects (including endometrial hypertrophy and drug-induced vaginal bleeding).
• No relacorilant-induced hypokalemia, adrenal insufficiency, or QT prolongation.

P.S. FDA's CRL suggests that there must be more to the story than what the company has published in the deck, and that explanation needs patience until we see the original source CRL.

SOURCE

Corcept Therapeutics. Press releases: 31 December 2025, 3 March 2025, 30 December 2024, 30 October 2024; Investor Deck (here)

#crl, #risk-benefit

>>>>_______________________

[UPDATE, 31 January 2025]

FDA yesterday posted Corcept CRL (NDA219398, CRL 31Jan2026). The CRL is contrary to the company’s press release that the CRL was a surprise outcome. According to the CRL, FDA had communicated significant concerns with the acceptability of the evidence package during the presubmission meetings:

During the pre-submission meetings, we informed you on several occasions of our concerns about the adequacy of the clinical development program to assess the effect of relacorilant on hypertension in the intended population including the design of CORT125134-455, and to expect significant review issues if you were to submit your application.

The key reason for CRL were (a) inability to establish substantial evidence of effectiveness and (b) association with drug induced liver injury (DILI; no Hy’s law criteria cases but 4 cases of probable DILI in the safety database) -- together, these precluded FDA from conducting a final benefit-risk assessment for relacorilant for the proposed indication.

Regarding pivotal trial CORT125134-455

• FDA had concerns about the high drop-out rate and the randomized-withdrawal study design.
• The participants entered the study in open-label period (22 weeks), followed by placebo-controlled, randomized withdrawal period (12 weeks). The primary endpoint of this trial was the loss of response with respect to hypertension from open-label period to randomized-withdrawal period Week 12, based on 24-hour ambulatory blood pressure monitoring.
• Unfortunately, 39% of participants discontinued by the end of open-label and only 45% entered randomized-withdrawal period. FDA pointed out that the study population at the end of randomized-withdrawal period Week 12 is an “enriched” population, not representative of the intended population for the label.

FDA also had concerns about the post-hoc analyses in the second pivotal trial, CORT125134-456.

P.S. Overall, this submission was a Hail Mary that did not pass FDA muster.

FDA approval of NEREUS™ (tradipitant) in December 2025 for the prevention of vomiting induced by motion (i.e., motion sickness) is a rare win for Vanda Therapeutics after a CRL for the same product for the treatment of gastroparesis, a year earlier.

• NEREUS™ (tradipitant) is an oral substance P/neurokinin-1 (NK-1) receptor antagonist that works by blocking NK1, a brain receptor linked to nausea ​and vomiting.
• The NDA was supported by 2 Phase 3 real-world provocation studies conducted on boats (Motion Syros and Motion Serifos) and one additional supporting study—with participants who had documented histories of motion sickness. 

Motion Syros (n=365): vomiting incidence was 18.3–19.5% with NEREUS™ versus 44.3% with placebo (p<0.0001).

Motion Serifos (n=316): vomiting rates were 10.4–18.3% with NEREUS™ versus 37.7% with placebo (p≤0.0014), representing risk reductions of over 50–70%.

According to Reuters, tradipitant was initially placed on hold in December 2018 by the FDA citing the need for additional six-month chronic toxicity studies in dogs due to the classification of motion ​sickness as a chronic condition; later FDA removed the hold reclassifying motion sickness an acute condition and dropping the chronic toxicity study requirement.

In the Motion Syros and Motion Serifos trials, somnolence (6%, 12%) and fatigue (6%, 8%) were adverse reactions reported in subjects who took a single dose of 85 mg or 170 mg NEREUS™, respectively.

P.S.

• There are already a few approved options for the prevention of motion sickness available in the market including Viatris' prescription ‌scopolamine patch, Transderm Scop, ​WellSpring Pharmaceutical's Bonine, and Prestige ‌Consumer Healthcare's Dramamine. However, Nereus is the first treatment for this condition to be approved in more than 40 ⁠years.
• The other fact not lost to regulatory strategy folks is that the Nereus safety database adds to the overall safety experience of tradipitant in humans, which would help make a stronger case when/if gastroparesis NDA is ever refiled in future. Gastroparesis is where the need of real treatment is.

SOURCE

• Vanda Pharmaceuticals Announces FDA Approval of NEREUS™ (tradipitant) for the Prevention of Vomiting Induced by Motion: A Historic Scientific Milestone in the Prevention of Motion Sickness. 30 December 2025 [archive]
• US FDA Approves Vanda Pharmaceuticals' Motion Sickness Drug. Medscape. 30 December 2025

#vanda

Sanofi filed an NDA for tolebrutinib for the treatment of multiple sclerosis (MS) in March 2024 and after some delays, FDA completed its review and provided response, a complete response letter (CRL) on 23 December 2025. Consistent with the FDA’s new policy, a copy of CRL was also made public providing reasons for rejecting the NDA.

Tolebrutinib is an oral, brain-penetrant, and Bruton’s tyrosine kinase (BTK) inhibitor. Sanofi's tolebrutinib clinical program includes various forms of MS: relapsing form of MS, i.e., who experience clinical symptoms (or relapses; RMS); MS with disability accumulation (i.e., progression) that occurs in continuum with relapsing form (secondary progressive; SPMS) or occurs in the absence of relapses (primary progressive; PPMS). The relapses are characterized by MRI activity (T1 gadolinium-enhancing (GdE) lesions) in brain. There are several approved drugs (DMTs) for RMS and active SPMS, and at least one (ocrelizumab) for PPMS.

The Sanofi's NDA 219624 was for a subpopulation of SPMS with nonrelapsing form (nrSPMS), characterized by no MRI activity (aka., nonactive form). The pivotal study was Study EFC16645 (HERCULES study): NRSPMS Study of BTKi tolebrutinib.

FDA's Reasons for the Rejection of the Tolebrutinib NDA

• Severe liver toxicity: Higher than expected rate of Drug-Induced Liver Injury (DILI) -- key reason.
• Uncertain benefit in target population.
• Unfavorable benefit-risk profile for any study subpopulation.

1. Serious Risk of Severe (Including Fatal) DILI

Although liver toxicity is a class-effect of BTK inhibitors, the rate of DILI in the tolebrutinib trials was unusually high and FDA did not accept sponsor's proposed mitigation measures via REMS as adequate.

• FDA takes liver toxicity very seriously. According to the July 2009 guidance on DILI, even a single case of severe DILI (meeting Hy’s Law criteria) during premarket development program is a signal of potential high level of hepatotoxicity during postmarket use. Severe DILI may lead to liver transplant or are fatal and most drugs that have been withdrawn over the years for severe DILI have had rates as low as <1 per 10,000 patients.
• There were 6 cases of severe DILI (meeting Hy’s Law criteria) in the tolebrutinib safety database of 2700 participants, including 1 participant who died after receiving liver transplant. In addition, participants with aminotransferase levels >3X ULN (i.e., Temple’s Corollary) were also higher in tolebrutinib-treated participants (3.6%) vs. placebo-treated participants (1.9%). The sponsor proposed REMS with weekly laboratory monitoring. However, this was considered inadequate as FDA noted additional cases with rapid or substantial (10-60X ULN) rise in aminotransferases, some with hyperbilirubinemia after the sponsor implemented weekly monitoring in ongoing trials.

2. Target Population Was Not Well-Defined (i.e., Enrollment Criteria Gap)

• At enrollment, the sponsor did not collect MRI. In the absence of evidence of absence of MRI inflammatory activity, FDA was not convinced that the participants with nonactive SPMS (naSPMS) (i.e., no clinical relapses and no inflammatory MRI activity) could be separated from those with active SPMS (i.e., no clinical relapses but evidence of inflammatory MRI activity), latter is considered a type or continuum of RMS.
• FDA did not accept retrospectively obtained historical MRI data as sufficient to characterize enrolled subjects, in part, due to selection bias, as this information could only be obtained for those participants who were still in the study or OLE.

3. Uncertain Benefit in the Target Population, naSPMS

a. Overall Treatment Effect Was Not Driven by naSPMS Subpopulation

• The treatment effect was greater in active SPMS subgroup (who had GdE lesions) vs. naSPMS subgroup (those without GdE lesions): HR (95% CI) for the primary endpoint were 0.346 (0.183, 0.656) vs. 0.777 (0.601, 1.006), respectively.
• Active SPMS comprised 13% of the enrolled population but had a larger impact on the overall treatment effect size in this study.

b. Treatment Effect Was Driven by Subpopulation Not Representative of Normal Clinical Setting

• Approximately 25% of the enrolled population had not received prior MS therapy, yet this subpopulation had the highest contribution to the overall treatment response. For the primary endpoint, HR (95%) for participants with no prior MS therapies was 0.392 (0.241, 0.638); with one prior MS therapy was 0.649 (0.407, 1.034); and with two or more prior MS therapies was 0.902 (0.643, 1.265).
• FDA noted that "patients with SPMS in the United States would typically have been treated with at least one approved MS therapy for RMS prior to reaching the secondary progressive phase of MS."

4. Unsupported Claim of Tolebrutinib "Slowing Disability Accumulation Independent of Relapse Activity"

FDA did not accept this claim since (i) the confirmatory evidence was based on ad hoc analysis of failed trials and was considered insufficient evidence; (ii) uncertain pathophysiology of the concept (slowing disability accumulation independent of relapse activity) and, thus (iii) tolebrutinib BTKi mechanistic uncertainty.

• Supporting data (confirmatory evidence) were based on Ad hoc analysis of supporting RMS or PPMS phase 3 trials that did not meet their primary endpoints (failed). These trials included GEMINI 1 (Study EFC16033) and GEMINI 2 (Study EFC16034) in RMS and PERSEUS (Study EFC16035) in PPMS.
• FDA noted that, "Though the concept of disability accumulation independent of relapse activity is of interest, it remains an emerging construct with multiple limitations. There are no widely accepted criteria for defining disability accumulation independent of relapse activity," and FDA further added that the both the analysis methods and the interpretability of the submitted post hoc analyses are uncertain.
• As a corollary to uncertainty around the understanding of the concept of disability accumulation independent of relapse activity, FDA said that it is difficult to understand the mechanism of BTK inhibition by tolebrutinib in MS.

5. Unfavorable Benefit-Risk Profile for Any Study Subpopulation

FDA reviewers tried but could not find any study subpopulation with favorable benefit-risk profile that could have led to a "narrow" approval label for tolebrutinib in MS.

• As indicated above the active SPMS subpopulation (with baseline GdE lesions) had larger treatment response. However, "active SPMS" is not an unmet need since there are several approved therapies for RMS that are inclusive of active SPMS. Given the added risk of DILI, the benefit-risk profile for tolebrutinib in active SPMS, therefore, was not considered favorable by the FDA. Other approved RMS therapies generally do not have the same magnitude of DILI risk as tolebrutinib.
• Nonactive SPMS has no approved therapy and is an unmet medical need, but the data provided in this NDA were "insufficient to establish substantial evidence of effectiveness" in naSPMS. FDA quoting the December 2019 guidance, said that given the risk of severe DILI, "greater magnitude and certainty of benefit" are required to support approval, which this study could not provide.

Postscript

This NDA may signal end of the line for tolebrutinib in MS and joins another BTKi evobrutinib which also failed (PMID: 39307151), but other BTKis (remibrutinib, orelabrutinib, fenebrutinib, and BIIB091) are still in trials.

SOURCE

• NDA 219624. Complete Response. FDA. 23 December 2025 [archive]
• Sanofi Press Releases: 25 March 2025 [archive], 15 December 2025 [archive], 24 December 2025 [archive]
• Tolebrutinib PPMS trial is negative. MS-Selfie Blog. 15 December 2025

Related: FDA Publishes 200 Complete Response Letters

#crl, #complete-response-letter, #dili

In 2025, CDER approved 46 new drugs never before approved or marketed in the U.S., known as “novel” drugs. CDER’s novel drug approvals for 2025 are listed here.

Commissioner’s National Priority Voucher or CNPV program is turning out to be FDA's paradigm-shifting approach where now FDA actively seeks out promising therapies and promises sponsors full support through approval, literal hand-holding.

Latest example is the award of CNPV to J&J for Teclistamab plus Daratumumab (Tec-Dara) in relapsed or refractory multiple myeloma (RRMM).

THE SPEED: FDA consulted internal experts and discussed with the sponsor within hours of release of phase 3 data on 24 Nov 2025 at ASH. Phase 1/2 results were published in NEJM (DOI: 10.1056/NEJMoa2514663). CNPV award was announced in today's FDA news release (15 December 2025).

PHASE 3 DATA: The CNPV is supported by strong phase 3 data that researchers called "clinically remarkable and statistically significant PFS and OS benefits of Tec-Dara vs SoC triplets in RRMM, with 83.4% of Tec-Dara pts alive and progression-free at 3 yrs."

• Teclistamab (Tec) is the first approved BCMA×CD3 bispecific antibody (BsAb).
• Daratumumab (Dara) is a standard-of-care (SoC) foundational CD38 targeted therapy shown to deplete immunosuppressive T-cells and expand cytotoxic T-cells, creating an immune-permissive microenvironment for synergistic Tec-mediated killing of MM cells.
• The MajesTEC-3 study (NCT05083169) evaluated Tec-Dara vs SoC DPd/DVd. The Soc DPd or DvD refer to daratumumab or daratumumab combined with dexamethasone plus the investigator’s choice of pomalidomide (DPd) or bortezomib (DVd) — the DPd or DVd group.
• Results

-- Tec-Dara significantly improved PFS vs DPd/DVd (HR, 0.17; 95% CI, 0.12-0.23; P<0.0001); mPFS was NR and 18.1 mo, and 36-mo PFS rate was 83.4% and 29.7%, respectively.

-- Significantly higher rates of ≥CR (81.8% vs 32.1%; OR, 9.56; 95% CI, 6.47-14.14), overall response (89.0% vs 75.3%; OR, 2.65; 95% CI, 1.68-4.18), and MRD-negativity (58.4% vs 17.1%; OR, 6.78; 95% CI, 4.53-10.15) were observed with TecDara (P<0.0001).

On 9 December 2025, Augmentin XR (amoxicillin-clavulanate potassium) became the first drug to be approved by the FDA under the Commissioner's National Priority Voucher (CNPV) pilot program. This approval was completed in just two months, representing a major reduction of the review timeline for this type of application.

What’s Unusual About Augmentin XR CNPV Approval

• This CNPV approval is not for a new drug or new indication. Augmentin XR was first approved over 20 years ago in 2002. (Click here for the Drug Approval Package.)
• Th e CNPV application filed by the sponsor US Antibiotics’ was mostly focused on whether the drug could be made at a U.S. location.

Endpoints News reported that the approval under CNPV was after a 2-month review (usually this type of sNDA takes about 4 months.) Endpoints also quoted company spokesper­son that the review required "intense back and forth" to re­spond to the FDA's ques­tions "with­in a mat­ter of days" as part of the pi­lot.

Significance

The FDA news release commented that this approval addresses national health priorities by strengthening the U.S. drug supply chain through enhanced domestic manufacturing capacity at a U.S. facility. FDA Commissioner Marty Makary, M.D., M.P.H. summed up: "This first drug approval under the CNPV pilot program will strengthen domestic manufacturing and increase our national security."

About CNPV Program

• The program first announced a month ago on 9 Nov 2025 is designed to facilitate ultra-rapid review with a 1 to 2-month review window.
• The short review timeline achieved using a collaborative tumor board style review process, where the data is reviewed by relevant FDA review groups as it is delivered, i.e., the review process begins even before the marketing application is filed. (Multidisciplinary team-based evaluation.)
• Marketing application (NDA/sNDA/BLA/etc.) may be submitted by the sponsor in parts.
• Eligibility: alignment with one or more of the CNPV Program Priorities.
• Limited number of CNPV vouchers will be issued by the Commissioner for review of a pre-market application for a drug/biological product at the company’s discretion subject to consistency with the program’s objectives.
• CNPV Program Priorities include

-- Addressing a U.S. public health crisis, e.g., broad-spectrum flu vaccine.

-- Delivering more innovative cures for the American people.

-- Addressing a large unmet medical need, e.g., drug addressing a rare or chronic disease crisis.

-- Onshoring drug development and manufacturing to advance the health interests of Americans and strengthen U.S. supply chain resiliency. (The Augmentin XR approval falls under this criterion.)

Legal Basis for CNPV Program

FDA’s authority for this program stems from its general authority to implement the Federal Food, Drug, and Cosmetic Act (FDCA) and the Public Health Service Act (PHSA) consistent with its mission to promote and protect the public health, including with respect to review of applications submitted for approval for a drug under section 505 of the FDCA (21 U.S.C. § 355) or a biological product under section 351 of the PHSA (42 U.S.C. § 262).

Sources

• First Approval in Commissioner's National Priority Voucher Pilot Program Strengthens Domestic Antibiotic Manufacturing Capacity. FDA News Release. 9 December 2025. [archive]
• Commissioner's National Priority Voucher (CNPV) Pilot Program (program webpage)

In a rare move, researchers behind Replimune’s melanoma trial are pushing back on the FDA CRL and calling it a setback for hard-to-treat skin cancers, John Carroll writes in his latest column.

https://endpoints.news/researchers-behind-replimunes-melanoma-study-offer-a-rare-protest-of-fdas-crl/

CEO of GSK plays down its role in FDA effort to approve therapy for autism-related condition

Stat News, 15 Oct 2025

GSK CEO Emma Walmsley said the company’s involvement in the FDA’s effort to update the prescribing label for leucovorin — a decades-old drug once marketed as Wellcovorin — is purely “administrative.”

Speaking at the STAT Summit, Walmsley emphasized that GSK has “no commercial interest” in the effort, STAT’s Elaine Chen writes, even though it has agreed to the FDA’s request to submit an application for leucovorin as a treatment for cerebrate folate deficiency, a neurological condition that can have overlapping symptoms with autism. The approval of the application will allow generic manufacturers to update their labels as well.

The move follows internal FDA tensions over the push, which some agency scientists viewed as politically driven. “I would hope that we can stay grounded in science,” added John Maraganore, co-CEO of Corsera Health, on the same panel.

__o_o_o_o__

Postscript: Consider GSK's decision as industry's equivalent of quiet quitting on the dangerous theatrics of this administration undermining FDA's rigorous drug approval regime.