Clinical Catch-Up: SIFI, BeiGene and Novo Report New Data (Updated)

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SIFI, BeiGene and Novo Holdings shared promising updates this week on their proposed treatments for acanthamoeba keratitis, relapsed or refractory chronic lymphocytic leukemia (CCL) and myasthenia gravis.

SIFI Plans NDA in Rare Eye Disease for 2023 

SIFI shared positive results from its Phase III clinical trial of Akantior for acanthamoeba keratitis, a rare eye disease, just in time for World Sight Day. 

The 135-patient multiple-center study showed 84.8% of the participants reached a clinical resolution of the disease and associated inflammation within a median treatment period of four months. 

Additional analysis demonstrated that when corrected for risk and other factors, such as prior corticosteroid use, diagnosis delay and stage of the disease at baseline, the clinical resolution rate rose to 86.7%. This is similar to the widely used control treatment of PHMB 0.2mg/ml and propamidine 1.0 mg/ml. 

Separating Akantior from current therapies is that it is a monotherapy. If approved, it could become more widely available due to its simpler production requirements. 

The European Medicines Agency validated SIFI’s marketing authorization application for Akantior in May 2022. The company plans to file a new drug application with the FDA in 2023. 

BeiGene’s CLL/SLL Candidate Shows Superior PFS to Imbruvica

BeiGene announced positive topline outcomes from its Phase III ALPINE trial of Brukinsa (zanubrutinib) for patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL). 

Brukinsa achieved superior progression-free survival compared to Imbruvica (ibrutinib), according to a final analysis evaluated by an independent review committee and investigator.

The study consisted of 652 patients across China, Australia, Europe, New Zealand and the United States. They were randomized into two groups: those who took 160 mg of Brukinsa twice a day and those who took 420 mg of Imbruvica once daily until they reached disease progression or unacceptable toxicity. 

Full details of the trial will be shared at an upcoming medical congress or journal.

Novo Holdings’ Myasthenia Gravis Drug Safe and Clinically Significant

Novo Holdings' portfolio company NMD Pharma reported positive top-line results from a Phase I/IIa study of NMD670 for the treatment of myasthenia gravis.

NMD670, which has an orphan drug designation from the FDA, was found to be well tolerated and safe when used on healthy volunteers while patients demonstrated clinically significant status changes.

NMD670 is a first-in-class small molecular inhibitor of the skeletal muscle specific chloride ion channel. Researchers found that inhibiting the CIC-1 helps enhance neuromuscular transmission and can restore skeletal muscle function. The FDA granted the drug an orphan drug designation in September. 

NMD Pharma will publish the full details of the study in a peer-reviewed journal and at a leading industry conference in the following months.

Actinogen’s AD Drug Delivers Significant Effect in Early-Stage Disease, Key Biomarkers Named

Actinogen Medical announced positive biomarker data from its Phase IIa trial on Xanamem for the treatment of early-stage Alzheimer’s Disease. 

The biomarker trial was conducted on 72 patients with blood biomarker samples from the earlier Phase IIa XanADu study involving 185 participants. Patients diagnosed with mild AD, or those with an MMSE score of 20 to 26, were given 10 mg of Xanamem or a placebo daily for 12 weeks. The goals were to measure the drug’s impact on biomarker-positive AD patients and to determine if the drug had any short-term effects on blood biomarkers themselves. 

At the end of the study period, CDR-SB, a rating scale that measures cognition and function in early-stage AD, was found to be a suitable endpoint to measure Xanamem’s effect on patients over an observation period of at least 12 weeks. 

Patients with elevated pTau also saw changes in NTB, a scale that measures executive function, and MMSE, which measures cognition. In addition, no changes were seen in patients when evaluated for the original trial’s co-primary endpoints ADAS-Cog14 or ADCOMS. The researchers confirmed that the two might not be helpful endpoints for a short 12-week study. 

CDR-SB will be the primary endpoint in the upcoming six-month Phase IIb study.

Applied Therapeutics’ Galactosemia Drug Misses Key Endpoint But Promising Trend Merits Further Study

Applied Therapeutics’ Phase III trial on AT-007 (gavorostat) for children with classic galactosemia failed to achieve statistical significance compared to placebo, even after 12 months of treatment. 

However, hope is not lost just yet. Despite this outcome, researchers of the ACTION-Galactosemia Kids study found an efficacy trend that favors AT-007, particularly in patients with significant deficits in clinical performance at baseline. The drug candidate appeared safe and well tolerated throughout the 12-month period. 

Because of these observations, the study will continue to the next review in a blinded format at 18 months of treatment. Applied Therapeutics will also be meeting with the European Medicines Agency to discuss the potential submission of an MAA. 

AT-007 is a CNS penetrant aldose reductase inhibitor being developed to treat severe and rare neurological disorders, including SORD deficiency, PMM2-CDG and galactosemia. So far, the drug has demonstrated the capacity to reduce plasma galactitol levels in adults and children with galactosemia and reduce blood sorbitol levels in adults with SORD deficiency.

AT-007 has an orphan drug and pediatric rare disease designations from the U.S. FDA for galactosemia and PMM2-CDG and a fast track designation for galactosemia.

BrainStorm Shares Additional Biomarker In ALS Platform

BrainStorm Cell Therapeutics shared positive analyses on a new biomarker that supports its technology platform NurOwn’s effect on patients with amyotrophic lateral sclerosis.

In the Phase III trial on patients with advanced-stage ALS, NurOwn’s activity on cerebrospinal fluid biomarkers was compared to placebo across key ALS pathways such as neurodegeneration, neuroprotection and neuroinflammation. Previous trials demonstrated the technology’s ability to reduce neurodegeneration and neuroinflammation biomarkers and increase neuroprotective biomarkers over 20 weeks. 

Researchers evaluated biomarkers actions on patients with baseline ALSFRS-R scores of >25 and ≤25, or those to be affected by the floor effect of the scale. They found similar biological outcomes in ALS patients regardless of the level of disease progression at baseline, thus showing NurOwn’s multifaceted mechanism of action.

Details were presented at the 5th Annual ALS ONE Research Symposium. 

Immatics New Phase I Data Confirms Monotherapy Candidate’s Action vs Solid Tumors

The latest update from Immatics’ Phase I trial with ACTengine IMA203 confirms the proposed monotherapy’s positive effect on patients with recurrent and/or refractory solid cancers. 

The update covers the 27 patients who have already completed the Phase Ia dose escalation stage and the first five patients in the Phase Ib dose expansion stage who received IMA203. All throughout, the drug had remained well tolerated and reached objective responses across a wide range of cancers, including uveal melanoma, cutaneous melanoma, ovarian cancer, synovial sarcoma and head and neck cancer. 

Around 50% of the participants also demonstrated early signs of enhanced durability when they were treated with the target dose or higher with more than 1 billion TCR-T cells. 

Immatics is now waiting on results from two additional dose expansion cohorts: one where IMA203 is combined with an immune checkpoint inhibitor and the other with the company’s second-generation product candidate IMA203CD8. 

The company expects to announce more developments throughout 2023, along with the commencement of its planned first-in-human trial with its half-life extended bispecific against preferentially expressed antigen in melanoma (PRAME), TCER IMA402, in the same year.

Tenax’s Levosimendan Trial Demonstrates Safety and Efficacy In Oral Form

Tenax Therapeutics’ candidate treatment for patients with pulmonary hypertension with heart failure and preserved ejection fraction (PH-HFpEF), levosimendan, delivered positive outcomes from the Phase II HELP study.  

The trial started in 2019, and patients who had completed the program enrolled in an open-label extension study to evaluate the transition from weekly intravenous infusions to daily oral tablets. The extension hypothesized that daily oral dosing would not only eliminate risks from using IV-related therapies but also safely maintain levosimendan’s observed efficacy from IV dosing. 

This was observed to be true towards the end of Phase II. This now prompts Tenax researchers to move forward to Phase III testing. Levosimendan oral remained well tolerated without safety issues over a six-to-eight-week period. There were no serious adverse events reported. 

The data were presented at the Heart Failure Society of America Scientific Sessions 2022. 

Levosimendan IV is approved in over 60 countries for hospitalized patients with acutely decompensated heart failure. Tenax holds the North American rights to develop and commercialize oral and subcutaneous formulations.

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