Sanofi Shows Promising Results for BTK Inhibitors in Relapsing Multiple Sclerosis

Sanofi (NASDAQ:SNY) reported positive results for its drug candidate SAR442168 in patients suffering from relapsing forms of multiple sclerosis. The results pertained Phase 2b clinical trial of the drug. The study did not observe any new safety signals. Sanofi had acquired the global rights for the drug candidate from Principia Biopharma in November 2017 in a $76 million deal. Sanofi had been working actively to boost its multiple sclerosis development pipeline. The company paid $40 million in upfront payments for the deal.

The data showed that the BTK inhibitor significantly reduced disease activity associated with multiple sclerosis as measured using MRI. The Phase 2 study aimed to evaluate the dose-response relationship after 12 weeks of treatment with SAR442168. The measurement was done by determining the number of new brain lesions using MRI.

John Reed, MD, PhD, Sanofis Global Head of Research & Development said, "The effect on brain lesions seen in our Phase 2b study is encouraging. As we go forward, we will explore whether our brain-penetrant BTK inhibitor offers strong efficacy and exceptional safety for a broad spectrum of MS patients with either relapsing or progressive forms of disease. Our phase 3 program is moving rapidly to initiate four pivotal clinical trials." The BTK inhibitor regulates both adaptive i.e. B-cell activation and innate i.e. CNS microglial cells immune cells.

The trial studied the drug at four different doses ranging from 5mg to 60mg after 12 weeks. It also used placebo data collected at four weeks. The primary objective consisted of measuring the number of new Gd-enhancing T1 hyperintense lesions. The dose response data was analyzed using modeling and a multiple comparison procedure. At 60mg dose, there was 85% relative reduction of new Gd-enhancing T1 hyperintense lesions. The secondary objective involved the measurement of new or enlarging T2 hyperintense lesions. In this area, the drug candidate at 60mg dose showed 89 percent relative reduction compared to placebo.

The Phase 2b trial was a randomized, placebo-controlled, double-blind, cross-over, dose-ranging trial spread over a period of 12 weeks. One group consisting of 64 subjects received one of the four doses of the drug candidate for the first 12 weeks and then were turned to placebo arm for four weeks. The second group of 66 patients was given placebo for four weeks and then switched to dosing of SAR442168. This data was used for eliminating a dose response curve and for minimizing exposure to placebo.

SAR442168 is an oral, brain penetrant, selective small molecule inhibitor of BTK. During its Phase 1 study, the drug candidate demonstrated BTK binding and cerebrospinal fluid exposure. The company now plans to initiate late stage study for the drug. The main emphasis is to start four pivotal Phase III clinical trials.

Kiniksa Pharmaceuticals (NASDAQ:KNSA) reported positive results for its lead drug candidate vixarelimab for treating moderate to severe prurigo nodularis. The results pertained to a Phase 2a clinical trial involving 49 patients. Prurigo nodularis is a condition where hard itchy lumps are formed on the skin that propagate when scratched.

The Phase 2a clinical trial met its primary endpoint which was related to the change from baseline in Worst Itch Numeric Rating Scale at week 8 in comparison to placebo. The mean reduction in the treatment arm was -50.6 percent compared to -29.4 percent in the control arm. Thus, the reduction in weekly-average WI-NRS from baseline at Week 8 was statistically significantly greater in patients who received vixarelimab versus those who received placebo.

The percentage of vixarelimab recipients achieved a PN-IGA score of 0/1 at Week 8 compared to placebo recipients was also observed to be statistically significant. The majority of the patients receiving the drug also showed a clinically meaningful greater-than-or-equal-to 4-point weekly-average WI-NRS reduction at Week 8. John F. Paolini, MD, PhD, Chief Medical Officer of Kiniksa said, The potential impact and differentiation of the OSMR mechanism was demonstrated: in addition to the nearly 70% reduction in the median weekly-average WI-NRS at Week 8, a disease severity benefit was seen, with approximately a third of vixarelimab-treated patients attaining a clear or almost clear lesion score by Week 8.

Vixarelimab is an investigational fully human monoclonal antibody that targets OSMR, which in turn is responsible for mediating signaling of two main cytokines implicated in pruritus, inflammation and fibrosis. These two cytokines are interleukin-31 (IL-31) and oncostatin M. The Phase 2a trial was a randomized, double-blind, placebo-controlled study aiming to test the efficacy, tolerability, pharmacokinetics, and safety of vixarelimab in reducing pruritus in patients suffering from prurigo nodularis.

Immunomedics Inc. (NASDAQ:IMMU) reported receiving fast track approval for its lead drug candidate Trodelvy. The drug candidate is designed to treat adult patients suffering from metastatic triple negative breast cancer who have previously received at least two therapies for metastatic disease. Trodelvy is the first antibody-drug conjugate approved by the FDA especially for treating relapsed or refractory metastatic TNBC. It also has the distinction of being the first FDA-approved anti-Trop-2 ADC.

The drug candidate has been approved under the Accelerated Approval Program pathway of the FDA. Trodelvy was earlier given Breakthrough Therapy and Priority Review designations. The main criterion used for approval purpose are the Objective Response Rate and Duration of Response. Dr. Loretta M. Itri, Chief Medical Officer of Immunomedics said, This approval highlights the potential of our unique ADC platform and strengthens the premise that the Trop-2 antigen found in many solid cancers is an important target for drug delivery. We are committed to broadening the potential use of Trodelvy in other Trop-2-expressing cancers, especially those with unmet need. The drug comes with a black box warning pertaining severe diarrhea and neutropenia.

The Phase 2, a single arm study, showed that the drug candidate had an ORR of 33.3 percent while its median DoR stood at 7.7 months. These results were derived by local assessment of 108 adult patients suffering from TNBC. These patients had previously received a median of three systemic therapies in the metastatic setting.

Immunomedics recently reported that it has stopped the Phase 3 confirmatory ASCENT study of the drug candidate in patients suffering from metastatic TNBC. The study enrolled more than 500 patients and showed compelling efficacy across several endpoints, leading to earlier conclusion. The decision was taken upon the unanimous recommendation presented by the DSMC. Immunomedics expect the top-line data from the study to be available by mid-2020. The company believes that the drug candidate has the potential to become standard of care in the management of TNBC.

Thanks for reading. At the Total Pharma Tracker, we do more than follow biotech news. Using our IOMachine, our team of analysts work to be ahead of the curve.

That means that when the catalyst comes that will make or break a stock, weve positioned ourselves for success. And we share that positioning and all the analysis behind it with our members.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Link:

Sanofi's BTK Progress, And Other News: The Good, Bad And Ugly Of Biopharma - Seeking Alpha