TransCon TLR7/8 Agonist continued to be well-tolerated and demonstrated early signs of clinical activity as monotherapy or in combination with pembrolizumab
- Abstract for dose-escalation topline data accepted for an oral presentation at SITC 2022, November 8-12 in Boston
- Recommended Phase 2 dose to be evaluated in four indication-specific dose-expansion cohorts
The American Academy of Ophthalmology 2022 meeting took place in Chicago over the weekend, where industry leaders harnessed the power of gene therapies against wet AMD, geographic atrophy and more.
Janssen’s Gene Therapies Demonstrate Efficacy, Safety
Janssen reported preliminary findings from two of its gene therapy programs, showing good safety profiles and promising signs of efficacy for both.
In the Phase I/II MGT009 study of patients with the inherited retinal disease X-linked retinitis pigmentosa, botaretigene sparoparvovec demonstrated an adverse event profile that was expected and manageable. Most side effects were related to the surgery procedure and not the drug itself. Most toxicities were transient and resolved spontaneously, Janssen reported.
During the study’s dose escalation and expansion phases, botaretigene sparoparvovec resulted in functional improvement in every visual domain assessed, as compared with untreated controls. Pooling the low- and intermediate-dose cohorts also showed better retinal sensitivity after treatment with the gene therapy.
Botaretigene sparoparvovec is being developed and commercialized under a global collaboration between Janssen and MeiraGTx Holdings plc.
Janssen also presented data from a second gene therapy, JNJ-1887. Low, intermediate and high doses of the intravitreal candidate met the primary safety endpoint in a Phase I open-label and dose-escalation study of 17 patients with advanced dry age-related macular generation with geographic atrophy. Lesion growth rates also slowed down following treatment with JNJ-1887, indicating the potential of further evaluation.
Atsena Sees Early Success Against Leber congenital amaurosis
Atsena Therapeutics’ gene therapy candidate ATSN-101 led to clinically meaningful vision improvements in patients with GUCY2D-associated Leber congenital amaurosis (LCA1).
Assessed in a Phase I/II clinical trial, increasing doses of subretinal ATSN-101 led to significantly better retinal sensitivity in 15 LCA1 patients, along with a non-significant but substantial improvement in best-corrected visual acuity, the company reported. There were no serious adverse events associated with the candidate, and most treatment-emergent toxicities were mild and temporary.
A monogenic disease caused by mutations in the GUCY2D gene, LCA1 interferes with normal retina function and can lead to severe vision impairment and even blindness. There is no approved treatment for this disorder and Atsena aims to launch a pivotal trial for ATSN-101.
REGENXBIO/AbbVie Gene Therapy Eases Treatment Burden in Wet AMD
Early data from the Phase II AAVIATE trial revealed treatment with REGENXBIO’s RGX-314, whether through a subretinal or suprachoroidal route, meaningfully reduces the need for anti-VEGF injections in patients with wet age-related macular degeneration, the company reported.
RGX-314 also proved to be safe and effective leading to durable improvements in best-corrected visual acuity and central retinal thickness in treated patients. No serious adverse events were deemed attributable to RGX-314.
Developed in collaboration with AbbVie, RGX-314 is a gene therapy being evaluated as a potential one-time treatment for wet AMD. The candidate is delivered using an AAV8 vector and encodes for an antibody fragment that can target and deactivate the VEGF molecule. RGX-314 is also being studied in diabetic retinopathy with results expected later this year.
Apellis Slows Lesion Growth in Geographical Atrophy in Phase III
Post-hoc analyses of the Phase III OAKS study showed Apellis Pharmaceuticals’ pegcetacoplan can reduce the rate at which the loss of retinal sensitivity occurs in patients with geographical atrophy.
Compared with the sham-control group, patients treated with Apellis’ candidate developed significantly fewer scotomatous points - areas in the retina that have completely lost light sensitivity and function, the company reported. Both beneficial effects increased over time and were significant in patients given pegcetacoplan monthly or every other month.
Pegcetacoplan’s safety profile was consistent with what had already been established in prior studies. Over the 2-year analysis period, new-onset exudations occurred at a rate of 12.2% in patients dosed monthly and 6.7% in those treated every other month.
The rate of exudation was 3.1% in sham controls. Incidences of infectious endophthalmitis and intraocular inflammation did not differ from other intravitreal therapies.
The marketing authorization for pegcetacoplan is under the FDA’s review and is set to receive a decision in November.
https://www.biospace.com/article/aao-2022-janssen-regenxbio-apellis-and-more/
Biotech company Zealand Pharma A/S, an innovator in peptide-based medicines, announced the positive topline results from its phase 3 trial of glepaglutide on Friday.
A total of 106 patients with short-bowel syndrome (SBS) who also experienced intestinal failure and dependency on parenteral support (PS) at least three days per week took part in the evenly randomized double-blind trial, receiving treatment with 10mg glepaglutide either once or twice weekly, or a placebo.
It was found that glepaglutide, a long-acting GLP-2 analogue, when given twice weekly as subcutaneous delivery via auto-injector in SBS patients met the primary endpoint in the EASE 1 phase 3 trial.
The study found that total weekly volume of perenteral support at 24 weeks was statistically significantly reduced compared to placebo (p=0.0039). In the twice weekly group, 66% of patients had a clinically meaningful response.
Once weekly delivery treatment with glepaglutide also resulted in a numeric reduction of weekly parenteral support, but was not of statistical significance, and a total of nine participants treated with glepaglutide were weaned of parenteral support and achieved enteral autonomy.
At the end of the 24 weeks, average reduction in parenteral support from baseline was 5.13 litres/week in twice-weekly glepaglutide dosed patients and 3.13 litres/week in those dosed once per week. Placebo treatment resulted in a reduction in parenteral support of 2.85 litres/week.
Glepaglutide was found to be apparently safe and well-tolerated in the EASE 1 trial, the most frequently reported adverse events being injection site reactions and gastrointestinal events.
Dr David Kendall, chief medical officer of Zealand Pharma, said: “We are extremely pleased with the results of the phase 3 EASE 1 trial […] We are particularly encouraged that a number of patients treated with glepaglutide were able to significantly reduce the burden of parenteral support.”
“We look forward to seeing the results of the ongoing EASE 2 and 3 long term extension trials and engaging with the regulatory authorities as we plan for submission of our NDA,” he continued.
An EASE 4 phase 3b trial is also planned to assess long-term effects of glepaglutide on intestinal fluid and energy uptake.
Dr Adam Steensberg, chief executive officer of Zealand Pharma, said: “We are enormously privileged to have such a rich pipeline of proprietary peptides that in the last six months have reported two positive phase 3 trials for two separate programs aimed at changing the lives of patients living with rare and severe diseases.”
SBS, a complex chronic and severe condition associated with reduced or complete loss of intenstinal function, often results in patients having to be connected to infusion lines and pumps every day. They are also at risk of serious and life-threatening complications, such as sepsis, blood clots, liver damage, and renal impairment.
https://pharmaphorum.com/news/positive-phase-3-results-for-zealand-pharmas-glepaglutide/
PRA052 is a monoclonal antibody blocking CD30 ligand that has a pleiotropic effect on both innate and adaptive immunity and targets a pathway that is distinct from TNF -
- PRA052 is the second clinical candidate identified using the Prometheus360™ platform with one of the strongest genetic associations to IBD and is linked to a broad range of immune-mediated diseases -
- Initiation of Phase 1 study of PRA052 expected in 4Q 2022 -
The FDA has a relatively light calendar for October with Theratechnologies' Trogarzo for HIV, Alnylam's Lumasiran for advanced primary hyperoxaluria, scPharmaceuticals' Furoscix for heart failure, and more.
Here's a look at the agency's schedule for the month.
Theratechnologies' Trogarzo for HIV
Theratechnologies has a target action date of Oct. 3 for its supplemental Biologics License Application (sBLA) for an IV Push formulation of Trogarzo for HIV. Trogarzo is a CD4-directed post-attachment HIV-1 inhibitor. The new formulation is more convenient. It can allow an infusion within 30 seconds without dilution compared to the 15-minute infusion time of the original IV formulation.
The submission was based on results from the TMB-302 Phase III trial, which Theratechnologies' partner, TaiMed Biologics, ran. The study hit the primary endpoint with a 90% confidence interval of the ratio of IV Push to IV Infusion with no serious adverse events. It also hit two secondary endpoints, demonstrating no difference in HIV-1 viral load from the change to IV Push and no detection of anti-Trogarzo antibodies.
Alnylam's Lumasiran for Advanced Primary Hyperoxaluria Type 1
Alnylam Pharmaceuticals has a target action date of Oct. 6 for its sNDA for lumasiran to reduce plasma oxalate for patients with advanced primary hyperoxaluria type 1 (PH1). Under the brand name Oxlumo, the drug was approved by the FDA in 2020 for treatment of PH1 to lower urinary oxalate levels in pediatric and adult patients.
The sNDA was based on positive six-month data from the ILLUMINATE-C trial, which demonstrated the drug substantially decreased plasma oxalate levels in patients with compromised renal function from PH1, including patients on hemodialysis.
scPharmaceuticals' Furoscix for Worsening Heart Failure
scPharmaceuticals has a target action date of Oct. 8 for the resubmission of its NDA for Furoscix. The drug is a proprietary formulation of furosemide delivered by an on-body infusor to treat congestion in patients with worsening heart failure. The drug is formulated to a neutral pH, which allows for subcutaneous infusion via a wearable pre-programmed on-body drug delivery system allowing for outpatient self-administration.
"The resubmission and acceptance of our Furoscix NDA was a significant achievement for our company and potentially gives us line-of-sight to transitioning to a commercial-stage company," stated John Tucker, CEO of scPharmaceuticals. "We believe the NDA addresses all concerns and questions raised in the Complete Response Letter that we received from the FDA in December 2020. As a result, we are preparing for a commercial launch of FUROSCIX, if approved, in the fourth quarter of this year."
Harrow's AMP-100 for Eye Anesthesia and Pain Management
Harrow Health had a target action date of Oct. 16 for its NDA for AMP-100. The drug was being considered for ocular surface anesthesia and intraoperative pain management during ocular surgery. On Sept. 27, the FDA approved it for that indication under the brand name Iheezo (chloroprocaine hydrochloride ophthalmic gel) 3%.
Harrow Health acquired the drug from Sintetica in July 2021. The NDA was based on data from a Phase III trial that successfully compared its efficacy and tolerability to current standards of care.
"We have always believed in the unique clinical value of Iheezo, and now that Iheezo is approved for use in the U.S. market, it has the potential to become an indispensable premium tool for eyecare professionals and their patients requiring ocular surface anesthesia," stated Mark L. Baum, chairman and CEO of Harrow.
Ipsen's Palovarotene for Heterotopic Ossification with Fibrodysplasia Ossificans Progressiva
The FDA's Endocrinologic and Metabolic Drugs Advisory Committee is meeting on Oct. 31 to discuss Ipsen Biopharmaceuticals' NDA for palovarotene capsules. The proposed indications are for the prevention of heterotopic ossification in adults and children, specifically females eight years and older and males 10 years and older, with fibrodysplasia ossificans progressiva (FOP).
FOP is an ultra-rare genetic disorder that results in bone forming where it shouldn't, such as outside of the skeleton and in the soft and connective tissues like the muscles, tendons and ligaments. Bones forming outside the skeleton are called heterotopic ossification.
The FDA has assigned a target action date of Dec. 29 for the application after the company resubmitted the NDA for Priority Review. The NDA was originally accepted on May 28, 2021; then the company withdrew it on Aug. 13, 2021.
