The investigational product is an extended-release tablet formulation of diazoxide chloride (DCCR), the crystalline salt of diazoxide. In patients with Prader-Willi syndrome, DCCR is expected to reduce hyperphagia through activation of the adenosine triphosphate–sensitive potassium channels in the hypothalamus.

The designation was supported by data from a phase 3 clinical development program that included patients 4 years of age and older with genetically confirmed PWS. In the double-blind, placebo-controlled DESTINY PWS trial (ClinicalTrials.gov Identifier: NCT03440814), study participants were randomly assigned to receive DCCR (n=82) or placebo (n=42). Findings showed DCCR significantly improved hyperphagia in patients with severe hyperphagia at baseline. Significant improvements in body composition were also observed.

In the open-label extension study (ClinicalTrials.gov Identifier: NCT03714373), patients enrolled in the DESTINY PWS trial were assessed following 1 year of DCCR administration. Results showed DCCR was associated with significant improvements in hyperphagia and PWS-related behaviors (eg, anxiety, compulsivity, disordered thinking, aggressive/disruptive behaviors). 

“The granting of Breakthrough Therapy designation, the first for a drug being developed for the treatment of PWS, marks another important milestone for our DCCR clinical development program,” said Anish Bhatnagar, MD, CEO  of Soleno Therapeutics. “This important designation is confirmation that the FDA views PWS as a serious condition and is an indication of DCCR’s potential to be a safe and effective treatment for PWS. We remain focused on preparing our NDA submission for DCCR in PWS, which we continue to expect will occur in mid-2024.”

Diazoxide choline previously received the FDA’s Orphan Drug and Fast Track designations for PWS.

The double-blind, active comparator-controlled phase 3 STRIDE-10 trial (ClinicalTrials.gov Identifier: NCT05569954) evaluated the safety and immunogenicity of V116 in pneumococcal vaccine-naïve adults 50 years of age and older (N=1484). Study participants were randomly assigned to receive a single dose of either V116 or PPSV23. 

The primary outcome measures included serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) at day 30 post vaccination and the percentage of participants with at least a 4-fold rise from baseline in serotype-specific OPAs. 

Results showed V116 elicited noninferior immune responses compared with PPSV23 for the 12 serotypes common to both vaccines. Additionally, superior immune responses were observed for the 9 serotypes included in V116 but not in PPSV23, and for 8 of 9 serotypes to V116 compared with PPSV23, as measured by the proportions of participants with at least a 4-fold rise in immune responses. 

“Even with the availability of current pneumococcal conjugate vaccines for adults, gaps in serotype coverage for invasive pneumococcal disease persist,” said Dr Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “These data add to the evidence supporting the potential for V116 to become an important new preventive option for adults, with results showing V116 elicited immune responses to the serotypes responsible for the majority of adult invasive pneumococcal disease.”

V116 is currently under Priority Review by the Food and Drug Administration (FDA) for the prevention of invasive pneumococcal disease and pneumococcal pneumonia caused by S. pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B in adults 18 years of age and older.

Tapinarof is an aryl hydrocarbon receptor agonist currently marketed under the brand name Vtama^® for the topical treatment of plaque psoriasis in adults.

The sNDA is supported by data from the phase 3 ADORING-1 and ADORING-2 trials (ClinicalTrials.gov Identifier: NCT05014568, NCT05032859, respectively), which included pediatric and adult patients with atopic dermatitis that was present for at least 6 months for individuals 6 years and older or 3 months for those 2 to 5 years of age. 

The primary endpoint for both studies was the proportion of patients who achieved a validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) with a minimum 2-grade improvement from baseline to week 8. In both trials, a significantly greater proportion of patients treated with tapinarof cream achieved vIGA-AD success compared with those who received vehicle.

“The FDA acceptance of our sNDA is an important milestone in our efforts to bring Vtama cream, as a potentially safe and well-tolerated nonsteroidal treatment option, to adults and children as young as 2 years old who suffer from atopic dermatitis,” said Todd Zavodnick, CEO of Dermavant. “Our commitment to patients is unwavering, and we remain highly focused on preparing for the commercial launch of Vtama cream, subject to FDA approval, for its second indication of atopic dermatitis.”

A regulatory decision is expected in the fourth quarter of 2024.

CTX-009 is a bispecific antibody that simultaneously blocks Delta-like ligand 4 and vascular endothelial growth factor A signaling pathways. The designation is supported by data from an open-label, single-arm phase 2 study (ClinicalTrials.gov Identifier: NCT04492033), which evaluated the safety, tolerability, and pharmacokinetics of CTX-009 in combination with paclitaxel in patients with unresectable advanced, metastatic or recurrent biliary tract cancer (N=24).

Findings showed an overall response rate (ORR) of 37.5% (95% CI, 18.8-59.4). Median duration of response and progression free survival were 9.4 months for both endpoints. Median overall survival was 12.5 months.

CTX-009 is currently being evaluated in combination with paclitaxel in the phase 2/3 COMPANION-002 study (ClinicalTrials.gov Identifier: NCT05506943) in adults with unresectable advanced, metastatic or recurrent biliary tract cancers who have received 1 prior systemic chemotherapy regimen. Topline data are expected by the end of 2024. 

“We are delighted that CTX-009 has received FDA Fast Track Designation highlighting the large unmet need in patients with advanced BTC where current therapies have low, single digit response rates, and limited effect on patient survival,” said Thomas Schuetz, MD, PhD, Co-founder, President of R&D, and Vice Chairman of the Compass board.

PNPO deficiency is a rare neurometabolic disorder caused by mutations in the PNPO gene, which is required for the production of normal levels of pyridoxal 5′-phosphate. The disorder is characterized by the onset of drug-resistant seizures in the first year of life. MC-1 is an investigational agent that contains pyridoxal 5′-phosphate monohydrate, an active vitamin B6 metabolite.

A phase 3, open-label study (MEND-PNPO; ClinicalTrials.gov Identifier: NCT04706013) evaluating MC-1 in patients with confirmed PNPO deficiency (via genetic analysis) is currently in the works, according to Medicure Inc. Patients will receive MC-1, a pharmaceutical grade pyridoxal 5′-phosphate, as an oral tablet.

The primary endpoint of the trial is overall survival time; the study group will be compared to a historical control group. Seizure frequency will also be assessed as a secondary outcome measure.

The FDA’s Fast Track designation helps to accelerate the development and review of products for serious and life-threatening conditions where no treatment exists or where the investigational therapy is likely to provide an advantage over currently available treatments.

The sBLA is supported by data from part 1 of the randomized, double-blind, multicenter phase 3 RUBY trial (ClinicalTrials.gov Identifier: NCT03981796), which evaluated the efficacy and safety of dostarlimab-gxly plus chemotherapy (carboplatin and paclitaxel) followed by dostarlimab-gxly vs placebo plus carboplatin-paclitaxel followed by placebo. The primary outcome measures were progression free survival and overall survival (OS).

Findings showed in the overall study population, treatment with dostarlimab-gxly plus chemotherapy reduced the risk of death by 31% vs placebo plus chemotherapy (hazard ratio [HR], 0.69 [95% CI, 0.539-0.890]; P =.002). Median OS was 44.6 months (95% CI, 32.6, not reached) in the dostarlimab-gxly plus chemotherapy arm and 28.2 months (95% CI, 22.1-35.6) in the placebo plus chemotherapy arm.

In a prespecified exploratory analysis of the MMRp/MSS population, treatment with dostarlimab-gxly plus chemotherapy reduced the risk of death by 21% vs placebo plus chemotherapy (HR, 0.79 [95% CI, 0.602-1.044]). Median OS was 34 months (95% CI, 28.6-not reached) in the dostarlimab-gxly plus chemotherapy group and 27 months (95% CI, 21.5-35.6) in the placebo plus chemotherapy group.

A regulatory decision on the sBLA is expected on August 23, 2024.

Dostarlimab-gxly is currently marketed under the brand name Jemperli for use in combination with carboplatin and paclitaxel in the treatment of adults with primary advanced or recurrent endometrial cancer that is either mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H).

Recessive dystrophic epidermolysis bullosa (RDEB) is characterized by extensive blistering and severe skin wounds caused by a mutation in the COL7A1 gene. Prademagene zamikeracel (pz-cel) is an autologous cell therapy that consists of epidermal sheets that deliver functional COL7A1 genes into the patient’s own skin cells to enable normal type VII collagen expression and facilitate wound healing.

In the letter, the FDA requested the Company provide additional information to satisfy Chemistry Manufacturing and Controls (CMC) requirements before a decision on approval could be made. The deficiencies noted in the CRL were not related to efficacy or safety data. No additional clinical trials were required to support the approval.

The BLA was supported by data from the phase 3 VIITAL study (ClinicalTrials.gov Identifier: NCT04227106), which evaluated the safety and efficacy of pz-cel in the treatment of large, chronic RDEB wounds. The trial included 43 large chronic wound pairs in 11 patients with RDEB. Findings showed 81.4% of pz-cel-treated wounds achieved 50% or greater wound healing compared with 16.3% of untreated control wounds (P <.001). Additionally, a statistically significant improvement in pain reduction associated with wound dressing changes was observed with pz-cel when compared with untreated control wounds (P =.0002).

“While we are surprised and disappointed by this CRL, we are committed to providing the CMC information necessary to respond to the agency’s asks, with the goal of bringing pz-cel to patients with RDEB as quickly as possible,” said Vish Seshadri, CEO  of Abeona. “We are already hard at work generating the additional CMC information, and we expect that all of FDA’s requests will be addressable in a reasonable timeframe. We anticipate completing the BLA resubmission in the third quarter of 2024 with necessary updates to fully satisfy all the deficiencies outlined in the CRL.”

The randomized, double-blind LUNA 3 study (ClinicalTrials.gov Identifier: NCT04562766) evaluated the safety and efficacy of rilzabrutinib, an oral, reversible, covalent Bruton tyrosine kinase inhibitor, in adult and adolescent patients with persistent or chronic ITP. At baseline, the median platelet count was 15,000/μL. Study participants had received a median of 4 prior ITP therapies.

Patients were randomly assigned to receive either rilzabrutinib 400mg orally twice a day or placebo through a 12- to 24-week double-blind period, followed by a 28-week open-label treatment period, and then a 4-week safety follow-up or long-term extension period. 

Findings showed a statistically significantly higher proportion of adult patients who received rilzabrutinib achieved platelet counts at or above 50,000/μL for at least 8 out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy (primary endpoint). Improvements in key secondary endpoints (ie, number of weeks with and time to platelet responses, rescue therapy use, physical fatigue, bleeding score) were also observed.

The Food and Drug Administration (FDA) previously granted Fast Track designation to rilzabrutinib for this indication. Detailed study results will be presented at a medical congress later this year. The adolescent portion of the study is ongoing.

AB-1002 is an investigational one-time gene therapy that promotes increased production of protein inhibitor 1. It is designed to inhibit the action of protein phosphatase 1, which has been linked to heart failure. 

Preliminary results from a phase 1 study (ClinicalTrials.gov Identifier: NCT04179643) showed clinically meaningful improvements in left ventricular ejection fraction, NYHA Functional Class, Minnesota Living with Heart Failure Questionnaire, cardiopulmonary exercise test, and 6-minute walk test at 12 months following intracoronary infusion of AB-1002.

The Company is currently enrolling participants in the phase 2 GenePHIT trial (ClinicalTrials.gov Identifier: NCT05598333) to evaluate the efficacy and safety of a single dose of AB-1002 administered via antegrade intracoronary artery infusion in patients with nonischemic cardiomyopathy and New York Heart Association (NYHA) Class III symptoms of heart failure.

“The Fast Track Designation for AB-1002 emphasizes the need to rapidly advance new therapeutic modalities such as gene therapy for people living with congestive heart failure,” said Christian Rommel, PhD, Head of Research and Development at Bayer’s Pharmaceuticals Division. “This designation underpins the potential of AB-1002 to address currently high unmet medical need, and we are excited about the opportunity to accelerate its development.”

The randomized, double-blind, placebo-controlled, SELECT-GCA study (ClinicalTrials.gov Identifier: NCT03725202) evaluated the efficacy and safety of upadacitinib in patients 50 years of age and older with GCA. Study participants were randomly assigned to receive either upadacitinib or placebo orally once daily, in combination with a 26-week steroid taper regimen. 

The primary endpoint was the percentage of patients who achieved sustained remission at week 52, defined as having achieved absence of GCA signs and symptoms from week 12 through week 52, and adherence to the protocol-defined steroid taper regimen. Findings showed 46% of patients treated with upadacitinib 15mg achieved sustained remission compared with 29% of those who received placebo (P =.0019). 

Moreover, 37% of patients in the upadacitinib 15mg arm achieved sustained complete remission (secondary endpoint) compared with 16% of those in the placebo arm (P <.0001). Sustained complete remission was defined as having an absence of GCA signs and symptoms from week 12 through week 52, adherence to the protocol-defined steroid taper, and normalization of both erythrocyte sedimentation rate and high sensitivity C-reactive protein from week 12 through week 52.

In the upadacitinib 15mg arm, fewer patients experienced at least 1 disease flare through week 52 compared with the placebo arm (34% vs 56%, respectively; P =.0014). No new safety signals were identified in the trial.

“I am encouraged by these results, which add to the body of evidence supporting the efficacy and safety profile of upadacitinib for the treatment of rheumatic diseases,” said Daniel Blockmans, MD, PhD, Department of General Internal Medicine, University Hospitals Gasthuisberg, Belgium, professor of medicine, KU Leuven, Belgium, and lead investigator of the SELECT-GCA trial. “Based on these results, upadacitinib has the potential to be the first oral treatment option for patients with GCA, a disease with inflammation of the large arteries that primarily impacts older people and has only one approved treatment to date commonly used with steroids.”

Full study results will be presented at a future medical meeting.

Upadacitinib, a Janus kinase (JAK) inhibitor, is currently approved under the brand name Rinvoq^® for rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn disease, ankylosing spondylitis, and non-radiographic axial spondyloarthritis. 

Tavapadon is an oral, once-daily, selective dopamine D1/D5 receptor partial agonist designed to improve motor control while avoiding D2/D3 overstimulation. The pivotal double-blind, randomized, placebo-controlled, parallel-group, flexible-dose TEMPO-3 trial (ClinicalTrials.gov Identifier: NCT04542499) evaluated the efficacy and safety of tavapadon as adjunctive therapy in patients with Parkinson disease who were on a stable dose of levodopa and were experiencing motor fluctuations (N=507). 

Study participants were randomly assigned to receive tavapadon 5 to 15mg orally or placebo once daily as adjunctive therapy for 27 weeks. The primary endpoint was the change from baseline in the total “on” time without troublesome dyskinesia based on the 2-day average of the self-completed home diary for motor function status (Hauser diary).

Results showed treatment with tavapadon led to a statistically significant and clinically meaningful increase of 1.1 hours in total “on” time without troublesome dyskinesia compared with placebo (1.7 hours vs 0.6 hours, respectively; P <.0001). Moreover, tavapadon met the key secondary endpoint demonstrating a statistically significant reduction in “off” time. Full study results will be submitted for presentation at future medical meetings.

“Tavapadon’s novel mechanism of action, which selectively activates the D1/D5 dopamine receptors, has demonstrated the potential to provide people living with Parkinson disease the right balance of motor control, safety and tolerability,” said Raymond Sanchez, MD, chief medical officer, Cerevel Therapeutics. “We are highly encouraged with the results announced today, and look forward to sharing additional data later this year from the monotherapy trials, TEMPO-1 and TEMPO-2, as we seek to evaluate tavapadon’s potential benefit to people living with Parkinson disease.”

Topline results from the phase 3 TEMPO-1 (ClinicalTrials.gov Identifier: NCT04201093) and TEMPO-2 (ClinicalTrials.gov Identifier: NCT04223193) trials are expected in the second half of 2024.

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist. It is the active ingredient in 2 Food and Drug Administration (FDA)-approved medications, Mounjaro for type 2 diabetes and Zepbound for chronic weight management.

The double-blind, phase 3 study (ClinicalTrials.gov Identifier: NCT05412004) included 2 groups of patients, those who were not on positive airway pressure (PAP) therapy (Study 1) and those who were (Study 2). To be included in the trial, patients had to have an apnea-hypopnea index (AHI) of at least 15 events/hour and a body mass index of at least 30kg/m². 

Study participants were randomly assigned to receive tirzepatide 10mg or 15mg (maximum tolerated dose) or placebo once weekly. The primary endpoint was the change from baseline in AHI at week 52. Secondary endpoints included the percent change in AHI from baseline and the percent change in body weight from baseline. 

Among OSA patients not on PAP therapy, the following efficacy results were reported for tirzepatide vs placebo at week 52:

• Efficacy estimand (efficacy prior to discontinuation of study drug):
  • Change in AHI from baseline: -27.4 events/hour vs -4.8 events/hour;
  • Percent change in AHI from baseline: -55.0% vs -5.0%; and
  • Percent change in body weight from baseline: -18.1% vs -1.3%.
• Treatment-regimen estimand (estimated average treatment effect regardless of treatment discontinuation):
  • Change in AHI from baseline: -25.3 events/hour vs -5.3 events/hour;
  • Percent change in AHI from baseline: -50.7% vs -3.0%; and
  • Percent change in body weight from baseline: -17.7% vs -1.6%.

Among OSA patients who were on PAP therapy and continued to use it, the following efficacy results were reported for tirzepatide vs placebo at week 52:

• Efficacy estimand:
  • Change in AHI from baseline: -30.4 events/hour vs -6.0 events/hour;
  • Percent change in AHI from baseline: -62.8% vs -6.4%; and
  • Percent change in body weight from baseline: -20.1% vs -2.3%.
• Treatment-regimen estimand:
  • Change in AHI from baseline: -29.3 events/hour vs -5.5 events/hour;
  • Percent change in AHI from baseline: -58.7% vs -2.5%; and
  • Percent change in body weight from baseline: -19.6% vs -2.3%.

The most common adverse events reported with tirzepatide were diarrhea, nausea, vomiting, and constipation.

“OSA impacts 80 million adults in the US, with more than 20 million living with moderate to severe OSA. However, 85% of OSA cases go undiagnosed and therefore untreated” said Jeff Emmick, MD, PhD, senior vice president, product development, Lilly. “Addressing this unmet need head-on is critical, and while there are pharmaceutical treatments for the excessive sleepiness associated with OSA, tirzepatide has the potential to be the first pharmaceutical treatment for the underlying disease.”

Additional data from the trial is expected to be presented at the American Diabetes Association’s 84th Scientific Sessions on June 21, 2024. The Company plans to submit the results from SURMOUNT-OSA to the FDA for regulatory review beginning mid-year.

The MenABCWY vaccine combines the antigenic components of Bexsero (meningococcal Group B vaccine) and Menveo (meningococcal Groups A, C, Y, and W-135 oligosaccharide diphtheria CRM₁₉₇ conjugate vaccine), reducing the number of injections to simplify immunization against invasive meningococcal disease. 

The application is supported by data from a phase 3 trial (ClinicalTrials.gov Identifier: NCT04502693) in which study participants received MenABCWY administered as 2 doses 6 months apart or 2 doses of Bexsero plus 1 dose of Menveo. Findings showed MenABCWY met the primary endpoint demonstrating noninferiority to 2 doses of Bexsero and 1 dose of Menveo for all 5 Neisseria meningitidis serogroups (A, B, C, W and Y).

In a separate confirmatory arm of the trial, MenABCWY demonstrated immunological effectiveness against 110 diverse meningococcal serogroup B invasive strains. The safety profile of MenABCWY was reported to be similar to Bexsero and Menveo.

A regulatory decision is expected on February 14, 2025.

LX2006 (AAVrh.10hFXN) is an adeno-associated virus gene therapy candidate designed to deliver a functional frataxin gene to cardiac cells to improve mitochondrial function. The designation was supported by preclinical data that showed LX2006 reversed cardiac abnormalities in disease models and improved cardiac function and survival.

The Company is currently evaluating LX2006 in patients with Friedreich ataxia cardiomyopathy in the 52-week, open-label, phase 1/2 SUNRISE-FA trial (ClinicalTrials.gov Identifier: NCT05445323). The dose escalation study is assessing the safety and tolerability of 3 different doses of LX2006. Cardiac function and other preliminary efficacy endpoints will also be investigated.

“The FDA’s Fast Track designation for LX2006 underscores the significant unmet need for effective treatment options to address the cardiac impact of this debilitating disease,” said R. Nolan Townsend, CEO of Lexeo Therapeutics. “We believe today’s Fast Track designation, along with the previously announced Rare Pediatric Disease and Orphan Drug designations granted to LX2006, will allow for enhanced regulatory interactions and the potential for this life-improving therapy to reach FA patients more quickly.”

Study 501 was a randomized, double-blind, placebo-controlled study (ClinicalTrials.gov Identifier: NCT04985942) that evaluated the efficacy and safety of lumateperone as an adjunctive treatment to antidepressants in 485 patients with MDD. Study participants were randomly assigned 1:1 to receive lumateperone 42mg or placebo once daily. At baseline, Montgomery-Åsberg Depression Rating Scale (MADRS) total scores were 30.4 for the lumateperone group and 30.0 for the placebo group.

Findings showed treatment with lumateperone met the primary endpoint demonstrating a statistically significant and clinically meaningful reduction in MADRS total score at week 6 vs placebo (least squares [LS] mean reduction: 14.7 points vs 9.8 points, respectively; LS mean difference: -4.9 points; P <.0001; Cohen’s d effect size = 0.61). 

Lumateperone was also associated with statistically significant improvements on the Clinical Global Impression Scale for Severity of Illness (CGI-S) at week 6 (P <.0001; Cohen’s d effect size =0.67) and in the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) scale (P <.0001) compared with placebo (both secondary endpoints). 

As for safety, the most common adverse events reported were dry mouth (10.8%), fatigue (9.5%) and tremor (5.0%). These events were mostly mild to moderate in severity.

“In this phase 3 study, lumateperone demonstrated a robust effect as an adjunctive treatment to antidepressants in patients with MDD who had inadequate response to antidepressant therapy,” said Dr Suresh Durgam, Executive Vice President, Chief Medical Officer of Intra-Cellular Therapies. “This study contributes to the growing body of evidence of lumateperone’s efficacy and safety across mood disorders.”

Topline results from a second phase 3 study evaluating lumateperone as adjunctive therapy in patients with MDD (Study 502; ClinicalTrials.gov Identifier: NCT05061706) are expected late in the second quarter of 2024. 

Lumateperone, an atypical antipsychotic, is currently marketed under the brand name Caplyta^® for the treatment of schizophrenia and depressive episodes associated with bipolar I or II disorder.

NM5072 is an investigational monoclonal antibody that selectively blocks properdin, a protein of the complement alternative pathway. Inhibition of properdin is expected to prevent lysis of red blood cells and thus improve anemia in patients with PNH.

In a phase 1 trial, 48 healthy volunteers were administered multiple doses of NM5072. Results showed the anti-properdin antibody was well tolerated and safe. Additionally, the duration of total alternative pathway inhibition was observed to be dose dependent. 

“This Orphan Drug designation approval represents a remarkable stride in therapeutic innovation, showcasing NM5072’s distinct capability to selectively inhibit the alternative pathway while safeguarding the classical pathway essential for combating infections in PNH patients,” said Robert Bard, VP Regulatory Affairs, NovelMed Therapeutics.

The Company is planning on a phase 2 trial that will include treatment-naïve PNH patients.

The FDA’s Orphan Drug designation is granted to medicines intended to treat or prevent rare diseases or disorders that affect fewer than 200,000 individuals.

SuVax is a subunit protein vaccine of recombinantly expressed Sudan ebolavirus glycoprotein. The designation was supported by nonhuman primate efficacy data, which showed the investigational vaccine provided 100% protection against SUDV infection. All the animals that received SuVax remained healthy and survived. The vaccine candidate has also been shown to be stable for at least 2 years when stored at temperatures of 40 degrees Celsius (104 degrees Fahrenheit).

“SuVax is based on our novel vaccine platform which includes 3 major components: a robust protein manufacturing process that has been demonstrated on multiple protein antigens, a novel nano-emulsion adjuvant which induces broad immunity, and a formulation procedure which enables thermostabilization of the combination of adjuvant and antigen in a single vial,” explained Oreola Donini, PhD, Senior Vice President and Chief Scientific Officer of Soligenix.

There are 4 ebolaviruses that are known to cause disease in humans. In 2019, the FDA approved the first Ebola virus vaccine, Ervebo; however, the vaccine only prevents disease caused by Zaire ebolavirus. “With recent outbreaks in 2022 and 2023, developing vaccines for all Ebola type diseases remains an important worldwide priority,” said Dr Donini.

The FDA’s Orphan Drug designation is granted to therapies intended to treat or prevent rare diseases or disorders that affect fewer than 200,000 individuals in the US.

Enibarcimab (formerly adrecizumab) is a first-in-class non-neutralizing monoclonal antibody that binds to adrenomedullin (ADM), a vasoprotective hormone. It is believed that modulating the ADM pathway may improve outcomes in patients with septic shock.

The Fast Track designation was based on data from the AdrenOSS-2 phase 2a biomarker-guided trial (ClinicalTrials.gov Identifier: NCT03085758), which included 301 patients with early septic shock and a bio-ADM plasma concentration at admission of at least 70pg/mL. Study participants were randomly assigned to receive a single infusion of enibarcimab or placebo. 

Results showed enibarcimab was well tolerated with the frequency and severity of adverse events being similar between the groups. Further subgroup analysis indicated that 2 biomarkers, ADM and circulating dipeptidyl peptidase 3 (cDPP3), could help identify patients who would benefit most from enibarcimab therapy. Compared with the total study population, the effect of enibarcimab on mortality improved in patients with lower cDPP3 values (<50ng/mL). 

In the low cDPP3 subgroup, the incidence of 28-day mortality in the enibarcimab arm was 16% compared with 25% for placebo (hazard ratio, 0.61 [95% CI, 0.34-1.08]; P =.085). In the total population, the incidence of 28-day mortality was 23% in the enibarcimab group vs 28% in the placebo group (HR, 0.84 [95% CI, 0.53-1.31]; P =.439).

“We are very confident that the use of enibarcimab in combination with 2 biomarkers, bio-ADM and cDPP3, holds the promise to become the first effective targeted treatment against septic shock,” said Dr Stephan Witte, CMO of AdrenoMed. “With AdrenoMed’s biomarker-guided approach it is possible to clearly define the patient population benefiting most from enibarcimab, resulting in a more pronounced treatment effect and leading to improved mortality in septic shock.”

The Company is currently preparing for a phase 2b/3 trial to confirm the benefits of enibarcimab.

The designation was based on early data from the phase 2 SELECT-AML-1 trial (ClinicalTrials.gov Identifier: NCT04905407), which compared the safety and efficacy of tamibarotene, an oral selective retinoic acid receptor alpha (RARα) agonist, in combination with venetoclax and azacitidine (triplet arm) to venetoclax and azacitidine (doublet arm) in newly diagnosed, unfit AML patients with RARA overexpression. The primary endpoint of the trial was complete response rate (CR)/complete response with incomplete hematologic recovery (CRi).

At the time of analysis, 19 patients were evaluable for response. Findings showed 100% of patients in the triplet arm (9/9) met the primary endpoint compared with 70% of patients in the doublet arm (7/10). In the triplet arm, 7 of the 9 response evaluable patients achieved a CR and 2 patients achieved a CRi. In the doublet arm, 3 of the 10 response evaluable patients achieved a CR and 4 patients achieved a CRi. The median time to CR/CRi was 21 days and 25 days for the triplet and doublet arms, respectively. By the end of cycle 1, 100% of patients in the triplet arm achieved CR/CRi vs 60% of those in the doublet arm.

As for safety, findings showed no additional safety signals or increased myelosuppression with the addition of tamibarotene to venetoclax and azacitidine. Most of the nonhematologic adverse events were reported to be low grade and reversible.

“We are pleased to receive Fast Track designation for tamibarotene for the treatment of AML,” said David A. Roth, MD, Chief Medical Officer of Syros Pharmaceuticals. “This designation reflects the tremendous need for a safe and effective therapy, which can improve the clinical outcomes and prognosis among people diagnosed with AML, many of whom cannot tolerate intensive treatment.

The Company expects to report additional data from SELECT-AML-1 later this year.

The multicenter, randomized, double-blind, placebo-controlled MONeT trial (ClinicalTrials.gov Identifier: NCT05842967) evaluated the immunogenicity and safety of Abrysvo in adults at risk of RSV-associated disease, including those with certain medical conditions (substudy A) and those who are immunocompromised (substudy B). 

Substudy A included 681 adults 18 to 59 years of age with chronic conditions who were randomly assigned 2:1 to receive a single dose of Abrysvo or placebo. Substudy B included approximately 200 immunocompromised adults 18 years of age and older who received 2 doses of Abrysvo (1 month apart).

Results showed Abrysvo met the coprimary immunogenicity endpoints demonstrating noninferior neutralizing responses for RSV-A and RSV-B when compared with responses seen in the phase 3 RENOIR study of Abrysvo in adults 60 years of age and older. Moreover, there was at least a 4-fold increase in neutralizing titers for RSV-A and RSV-B 1 month after receiving Abrysvo compared with prevaccination. The safety profile of Abrysvo was consistent with that observed in other patient populations.

“These encouraging results provide evidence that Abrysvo can help protect adults with increased risk against RSV-associated illness,” said Annaliesa Anderson, PhD, Senior Vice President and Head, Vaccine Research and Development, Pfizer. “We are excited to address a significant unmet need, pending regulatory authority approval, as Abrysvo has the potential to become the first and only RSV vaccine for adults 18 years and older.”

Abrysvo is currently approved for the prevention of LRTD caused by RSV in individuals 60 years of age and older. It is also indicated for active immunization of pregnant individuals at 32 through 36 weeks gestational age for the prevention of LRTD and severe LRTD caused by RSV in infants from birth through 6 months of age.

Barth syndrome is a rare genetic disorder characterized by muscle weakness and heart abnormalities, often resulting in heart failure, recurrent infections, delayed growth, and reduced life expectancy. Elamipretide is a peptide compound designed to penetrate cell membranes targeting the inner mitochondrial membrane where it binds reversibly to cardiolipin.

The application for elamipretide is supported by data from the SPIBA-001 phase 3 retrospective natural history control trial, which compared data from the open-label portion of the TAZPOWER phase 2/3 study (ClinicalTrials.gov Identifier: NCT03098797) to matched natural history controls. Findings showed treatment with elamipretide met the primary and most secondary endpoints demonstrating improvements in assessments of exercise tolerance, strength, and cardiac function.

Additionally, the effectiveness of elamipretide was supported by data from the TAZPOWER study in 12 male patients 12 years of age and older with genetically-confirmed Barth syndrome. Study participants were randomly assigned to receive elamipretide 40mg subcutaneously once daily for 12 weeks or placebo (part 1), followed by a 4-week washout and then 12 weeks in the opposite arm. In the open-label extension phase (part 2), 10 patients received elamipretide 40mg daily, of which 8 patients reached 36 weeks of treatment.

Results from part 2 showed treatment with elamipretide demonstrated significant improvements in the 6-minute walk test (primary endpoint; +95.9 m; P =.024) and the Barth Syndrome Symptom Assessment scale (-2.1 points; P =.031). Moreover, significant improvements were observed in knee extensor strength, patient global impression of symptoms, and certain cardiac parameters.

“We are pleased that the FDA has not only filed our NDA for Barth syndrome but has also committed to a transparent review process with its decision to convene an advisory committee,” said Reenie McCarthy, Chief Executive Officer. “We welcome the input of committee experts to advise FDA on the seriousness of this devastating disease and the urgency of the unmet need, including in light of FDA’s puzzling review designation.  We look forward to working with the FDA through the review process.”

This is the second CRL the Company has received for SPN-830. The drug/device combination therapy provides a continuous subcutaneous infusion of apomorphine through an infusion pump. Efficacy was established based on data from the phase 3 TOLEDO study (ClinicalTrials.gov Identifier: NCT02006121) and a supportive open-label study (ClinicalTrials.gov Identifier: NCT02339064).

In the letter, the FDA cited that additional information on product quality and the infusion device was still needed before the Agency could make a decision on approval. No clinical or safety issues were noted in the CRL.

“We remain committed to bringing SPN-830 to the market as an important treatment option for PD patients who experience motor fluctuations associated with off episodes,” said Jack Khattar, President & CEO of Supernus. “We will work with the FDA to address the CRL and to successfully resubmit our SPN-830 NDA.” 

Apomorphine, a non-ergoline dopamine agonist, is believed to treat off episodes associated with Parkinson disease through stimulation of postsynaptic dopamine D₂-type receptors within the caudate-putamen in the brain.

Bimekizumab, an interleukin (IL)-17A and IL-17F inhibitor, is currently approved under the brand name Bimzelx^® for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. 

The sBLA is supported by data from the phase 3 BE HEARD I and BE HEARD II studies (ClinicalTrials.gov Identifier: NCT04242446 and NCT04242498, respectively), which included more than 1000 adults with moderate to severe HS (defined as ≥5 inflammatory lesions) who had an inadequate response to a course of a systemic antibiotic. Patients were randomly assigned to receive either bimekizumab or placebo.

The primary endpoint was the percentage of patients who achieved clinical response as measured by Hidradenitis Suppurativa Clinical Response 50 (HiSCR50; defined as at least a 50% reduction from baseline in the total abscess and inflammatory nodule count with no increase from baseline in abscess or draining tunnel count) at week 16.

Results from both studies showed patients treated with bimekizumab achieved clinically meaningful improvements in HiSCR50 at week 16 compared with placebo. A greater proportion of patients who received bimekizumab also achieved HiSCR75 at week 16 (key secondary endpoint) vs placebo. 

Post-hoc analysis of the pooled phase 3 data from both trials, showed a greater proportion of bimekizumab-treated patients achieved draining tunnel reductions of 3 or more at week 16 vs placebo (58.0-70.6% vs 35% for placebo), with sustained or improved responses through week 48. Clinically meaningful improvements in skin pain were also noted in bimekizumab patients through week 48.

“The most recent sBLA seeks approval for Bimzelx in moderate to severe hidradenitis suppurativa, and is aligned to our goal of expanding the reach of Bimzelx to more patients living with IL-17–mediated diseases,” said Emmanuel Caeymaex, Executive Vice President, Immunology Solutions, and Head of US, UCB. “In addition, the sBLA for the 2mL device presentations aims to offer increased convenience for patients. Today, 1 dose of Bimzelx in moderate to severe plaque psoriasis is administered as two 1mL injections. Approval of the 2mL device presentations would mean that patients would have an alternative 1-injection regimen option.”

TransCon PTH for Hypoparathyroidism

PDUFA date: May 14, 2024

TransCon PTH (palopegteriparatide) is an investigational, once-daily, long-acting prodrug of parathyroid hormone (PTH[1-34]) designed to restore physiologic levels of PTH for 24 hours. The NDA is supported by data from the phase 3 PaTHway trial (ClinicalTrials.gov Identifier: NCT04701203) and the phase 2 PaTH Forward trial (ClinicalTrials.gov Identifier: NCT04009291), which evaluated the efficacy and safety of TransCon PTH in adults with hypoparathyroidism. Findings from the PaTHway trial showed a statistically significantly greater proportion of patients treated with TransCon PTH met the primary endpoint achieving serum calcium levels within normal range and independence from therapeutic levels of conventional therapy compared with placebo. In the PaTH Forward trial, long-term treatment with TransCon PTH provided a durable response, with 93% of patients achieving independence from conventional therapy with active vitamin D and therapeutic levels of calcium through week 110.

Rivoceranib Plus Camrelizumab for Unresectable Hepatocellular Carcinoma

PDUFA date: May 16, 2024

Rivoceranib is an orally-administered inhibitor of vascular endothelial growth factor receptor 2. Camrelizumab is a humanized monoclonal antibody that targets programmed death-1 (PD-1) receptor and is administered intravenously. The NDA is supported by data from the phase 3 CARES 310 study (ClinicalTrials.gov Identifier: NCT03764293), which compared the efficacy and safety of rivoceranib plus camrelizumab to sorafenib in 543 adults with advanced hepatocellular carcinoma who had not previously received systemic therapy. Findings showed rivoceranib plus camrelizumab demonstrated statistically significant and clinically meaningful prolonged overall survival and progression free survival vs sorafenib.

Lisocabtagene Maraleucel for Follicular Lymphoma

PDUFA date: May 23, 2024

Lisocabtagene maraleucel (liso-cel) is a CD19-directed genetically modified autologous T cell immunotherapy. It is currently approved under the brand name Breyanzi^® for adult patients with large B-cell lymphoma. The sBLA is supported by data from the TRANSCEND FL trial (ClinicalTrials.gov Identifier: NCT04245839), an open-label, phase 2 single-arm study evaluating liso-cel in patients with relapsed or refractory indolent B cell non-Hodgkin lymphoma, including high-risk second-line FL. Among the 101 relapsed/refractory FL patients in TRANSCEND FL, the overall response rate was 97% (95% CI, 91.6-99.4; P <.0001), with 94% achieving a complete response. At a median follow-up of 16.6 months, median duration of response was not reached; 81.9% of responders had an ongoing response at 12 months. At a median follow-up of 17.5 months, median progression free survival (PFS) was also not reached; 12 month PFS was achieved in 80.7% of patients.

Prademagene Zamikeracel for Recessive Dystrophic Epidermolysis Bullosa

PDUFA date: May 25, 2024

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare connective tissue disorder characterized by extensive blistering and severe skin wounds. It is caused by a mutation in the COL7A1 gene, resulting in the inability to produce type VII collagen. Prademagene zamikeracel (pz-cel) is an autologous cell therapy that consists of epidermal sheets that deliver functional COL7A1 genes into the patient’s own skin cells to enable normal type VII collagen expression and facilitate wound healing. The application is supported by data from the phase 3 VIITAL study (ClinicalTrials.gov Identifier: NCT04227106), which included 43 large chronic wound pairs in 11 patients with RDEB. Findings showed 81.4% of pz-cel-treated wounds achieved 50% or greater wound healing compared with 16.3% of untreated control wounds (P <.001). Additionally, a statistically significant improvement in pain reduction associated with wound dressing changes was observed with pz-cel when compared with untreated control wounds (P =.0002).

Lisocabtagene Maraleucel for Mantle Cell Lymphoma

PDUFA date: May 31, 2024

In addition to the follicular lymphoma indication, the FDA is expected to make a decision on the use of lisocabtagene maraleucel (liso-cel) for mantle cell lymphoma (MCL). The sBLA includes data from the TRANSCEND NHL-001 trial (ClinicalTrials.gov Identifier: NCT02631044), an open-label, phase 1, single-arm study assessing liso-cel in in a cohort of patients with relapsed or refractory MCL. The MCL cohort of TRANSCEND NHL-001 enrolled patients with relapsed or refractory disease after 2 or more prior lines of therapy, including a Bruton tyrosine kinase inhibitor (n=74). At a median follow-up of 16.1 months, the objective response rate was 86.5% (95% CI, 76.5-93.3; P <.0001), with 74.3% of patients achieving a complete response.