To evaluate the psychometric properties of the itch numeric rating scale (itch NRS), both the Worst Itch Numeric Rating Scale (WI-NRS) and the Average Itch Numeric Rating Scale (AI-NRS).

Design, Setting, and Participants:

This secondary analysis is based on a secondary end point of a phase 2 randomized clinical trial of serlopitant for treatment of pruritus associated with PN. This randomized, double-blind, placebo-controlled study was conducted at 15 sites in Germany. Eligible patients were aged 18 to 80 years and had generalized PN for more than 6 weeks that was refractory to previous antipruritic therapies. Patients were required to have a visual analog scale itch score of 7 or higher at screening. Data were collected from July 2014 to June 2016 and analyzed from June 2016 to January 2017.

Main Outcomes and Measures:

The itch NRS (AI-NRS and WI-NRS) was correlated together with the following measures: the electronic verbal rating scale (eVRS) for itch self-categorization, average itch visual analog scale (AI-VAS), worst itch visual analog scale (WI-VAS), the pruritus-specific quality-of-life rating instrument ItchyQoL, Dermatology Life Quality Index (DLQI), and Prurigo Activity and Severity Score (items 7b and 7a: percentage healed prurigo lesions and percentage of prurigo lesions with excoriations).

Results:

There were 123 participants in this study; the mean (SD) age of participants was 57.3 (11.58) years, and 58 (47.2%) were male. Strong associations (r ≥ 0.5) were observed between itch NRS items (WI-NRS and AI-NRS) and AI-VAS (24 hours) at weeks 2, 4, and 8 (r = 0.72-0.90; P < .001). Similar strong associations were also observed between itch NRS items and WI-VAS (24 hours) and eVRS for itch severity across weeks 2, 4, and 8 (r = 0.65-0.92; all P < .001). Strong correlations were seen between change scores for WI-NRS and WI-VAS and AI-VAS (r = 0.76 and 0.70, respectively; both P < .001). Similar findings were seen for AI-NRS, where correlations between change scores for WI-VAS and AI-VAS were 0.71 and 0.72, respectively (both P < .001). Analyses for the itch NRS items also showed that test-retest reliability was acceptable and provided evidence of acceptable convergent validity based on the eVRS and visit verbal rating score for itch self-categorization, ItchyQoL, and DLQI.

Conclusions and Relevance:

Results from this secondary analysis show that the itch NRS items WI-NRS and AI-NRS have good psychometric properties for pruritus associated with PN and should be considered acceptable tools for assessing pruritus in future clinical trials of PN.

Trial Registration:

ClinicalTrials.gov Identifier: NCT02196324.

2020-06-01·Journal of the American Academy of Dermatology1区 · 医学

Phase 2 trial of a neurokinin-1 receptor antagonist for the treatment of chronic itch in patients with epidermolysis bullosa: A randomized clinical trial

1区 · 医学

Article

作者: Nazaroff, Jaron ; Kwon, Paul ; Barriga, Melissa ; Shu, Kim ; Solis, Daniel C ; Li, Shufeng ; Bailey-Healy, Irene ; Choi, Sara ; Joing, Mark ; Chiou, Albert S ; Tang, Jean Y ; Dutt-Singkh, Yana

BACKGROUND:

Chronic pruritus causes major morbidity in epidermolysis bullosa (EB). The substance P-neurokinin 1 receptor (SP-NK1) pathway is a promising target for treating EB-related pruritus.

OBJECTIVE:

To evaluate the safety and efficacy of the oral NK1 receptor antagonist serlopitant in treating moderate-severe pruritus in EB.

METHODS:

The study randomized 14 patients to serlopitant or placebo for 8 weeks, followed by a 4-week washout and optional open-label extension. The primary end point was change in itch as measured by the Numeric Rating Scale. Secondary end points were change in itch during dressing changes and wound size.

RESULTS:

We observed greater itch reduction with serlopitant, equivalent to a 0.64-point comparative reduction on the 11-point Numeric Rating Scale by week 8, although this failed to meet statistical significance (P = .11). More serlopitant patients achieved ≥3-point reduction compared with placebo (43% vs 14%, P = .35). In post hoc analysis excluding 1 patient with a concurrent seborrheic dermatitis flare, serlopitant achieved significantly greater median itch reduction from baseline by week 4 (-2 points vs 0, P = .01). We observed no statistically significant differences in secondary end points. Serlopitant was well-tolerated.

LIMITATIONS:

Small sample size due to disease rarity.

CONCLUSION:

The potential itch reduction with serlopitant observed in this trial will be pursued by a larger powered trial (NCT03836001).

2020-06-01·Journal of the American Academy of Dermatology1区 · 医学

Serlopitant for psoriatic pruritus: A phase 2 randomized, double-blind, placebo-controlled clinical trial

1区 · 医学

Article

作者: Pariser, David M ; Spellman, Mary C ; Chien, Elaine ; Yosipovitch, Gil ; Lebwohl, Mark ; Bagel, Jerry

BACKGROUND:

Pruritus, a common symptom of psoriasis, negatively affects quality of life; however, treatment of lesional skin does not consistently alleviate psoriatic itch.

OBJECTIVE:

To examine the effects of serlopitant, an oral, once-daily neurokinin 1 receptor antagonist, for treatment of psoriatic pruritus in a phase 2, randomized clinical trial (NCT03343639).

METHODS:

Patients (n = 204) were randomized to receive serlopitant, 5 mg, or placebo daily for 8 weeks. Eligible adult patients had plaque psoriasis for ≥6 months, plaques covering ≤10% of body surface area, pruritus for ≥4 weeks, and Worst Itch Numeric Rating Scale (WI-NRS) score ≥7 at the initial screening.

RESULTS:

Participants (54.2% women) had a mean age of 47.5 years and 85.2% were white. Mean baseline WI-NRS scores were 8.3 for serlopitant and 8.1 for placebo. The WI-NRS 4-point response rate at 8 weeks (primary end point) was 33.3% for serlopitant vs 21.1% for placebo (P = .028); at 4 weeks the rates were 20.8% for serlopitant vs 11.5% for placebo (P = .039). Treatment-related adverse events were reported for 4.9% of serlopitant-treated and 4.0% of placebo-treated patients.

LIMITATIONS:

This was a phase 2 study with a small study population. Patients with severe psoriasis were excluded.

CONCLUSION:

Serlopitant significantly reduced pruritus associated with mild to moderate psoriasis, supporting continued development of serlopitant for this patient population.

项与 Menlo Therapeutics, Inc. 相关的新闻（医药）

2023-09-29

·FierceBiotech

Chutes & Ladders—Madrigal COO exits 2 weeks after new CEO Bill Sibold starts

None Welcome to this week's Chutes & Ladders, our roundup of hirings, firings and retirings throughout the industry. Please send the good word—or the bad—from your shop to Max Bayer or Gabrielle Masson, and we will feature it here at the end of each week. Madrigal’s executive overhaul not done yet Madrigal Pharmaceuticals New Madrigal Pharmaceuticals CEO Bill Sibold, just days into the role, has a critical new position to fill with Chief Commercial Officer Remy Sukhija heading for the exits. Sukhija had been with the company since April 2020. The company says he’s leaving to explore external opportunities but that he also qualifies for compensation associated with being terminated without cause. Two weeks ago, ex-Sanofi executive Sibold took the helm, with longtime CEO Paul Friedman stepping down. Friedman steered the ship for seven years, leading the company through its recent new drug application for its nonalcoholic steatohepatitis med resmetirom. The drug has the potential to be the first such approved treatment, with the FDA slated to decide its fate by mid-March 2024. That prospect makes the timing of Sukhija’s departure even more interesting. And it comes as the company’s share value has dipped in the last month, down more than 16% from $180.83 to $151.27. Disclosure Ex-Novartis CMO Tsai to lead biotech Forcefield Therapeutics Former Novartis Chief Medical Officer John Tsai, M.D., is moving to the biotech world, becoming CEO of London-based Forcefield Therapeutics. The company is working on treatments for heart health following post-myocardial infarction in order to prevent further heart failure. It's buoyed by funding from Syncona, where Tsai has been an executive partner since May. It's new territory for Tsai, who’s played in the Big Pharma arena since the turn of the century. He aptly was the cardiovascular team leader for Pfizer from 2000 to 2006 before spending 11 years at Bristol Myers Squibb. In 2017, Tsai was named the chief medical officer at Amgen, a role he kept when he moved to Novartis in May 2018. Tsai’s departure was announced just a couple of months before the company initiated plans for a larger restructuring that was estimated to eliminate some 8,000 jobs. The Swiss Pharma rehired Shreeram Aradhye, M.D., to lead global drug development when Tsai exited. Release Caren Deardorf named Editas’ new commercial and strategy chief Editas Medicine Editas Medicine has landed on a new chief commercial and strategy officer, naming Caren Deardorf to the role. She’ll lead the company’s commercial strategy and execution in addition to overseeing life cycle management efforts. Deardorf was the chief commercial officer of two prior biotechs: Magenta Therapeutics and Ohana Biosciences. Magenta’s efforts sputtered in early February after the death of a patient in a trial testing its leukemia drug left the company at the end of the clinical road. Ohana met a similar face in 2021, a year and a half after being launch by Flagship Pioneering. Prior to those roles, Deardorf was the VP of product development and commercialization at Biogen, helping lead the launch of Spinraza. Release > After 13 years at Merck KGaA, Klaus Urbahns, Ph.D., has left to become ProFound Therapeutics’ chief scientific officer. Urbahns most recently served as Merck KGaA’s head of EMD Serono R&D Institute, global head of discovery and development technologies, co-chair of the discovery-research committee and member of the Merck Ventures investment board. Release > PureTech has picked Robert Lyne to join as chief portfolio officer by January 2024. Lyne joins from Arix Bioscience, where he most recently served as CEO. Release > IQVIA has tapped Richard Staub III to serve as president of its research and development solutions business unit, taking the spot from Costa Panagos, who is retiring after 24 years with the company. Staub transitions to his new role from his former position as senior adviser to IQVIA’s chair and CEO. Release > Pacira BioSciences’ CEO and chair David Stack is retiring, though he has pledged to stay on until the board finds a successor. Stack has led the company focused on non-opioid pain management for 16 years. Release > hC Bioscience has selected Jose Lora, Ph.D., to serve as the tRNA company’s chief scientific officer. Before hC Bioscience, Lora served as chief scientific officer for Intergalactic Therapeutics and enGene. Release > Strata Oncology has chosen Goz Alhir to be the company's SVP of commercialization. Alhir has served in various roles across Eli Lilly, Onyx Pharmaceuticals, NanoString Technologies, Adaptive Biotechnologies and Caris Life Sciences. Release > Morphic Holdings’ CEO Praveen Tipirneni, M.D., is taking a leave of absence after suffering from an emergency medical event. The leader is expected to return, and the company doesn’t anticipate changes to its operations. Release > Turbine has tapped Bob Silverman to serve as the company’s first chief business officer. Before joining Turbine, Silverman served in CBO roles at Alloy Therapeutics, Rejuveron Life Sciences and C2i Genomics, and he spent almost three decades with Roche earlier in his career. > The Institute for Clinical and Economic Review, an independent, nonprofit research institute, has selected Daniel Ollendorf, Ph.D., as chief scientific officer and director of health technology assessment methods and engagement. Ollendorf served as ICER’s CSO from 2007 to 2018 and is currently a leader at Tufts Medical Center. Release > SaNOtize’s board has hand-picked Steven Basta to serve as CEO, replacing co-founder Gilly Regev, Ph.D., who will transition to chief strategy and innovation officer. Basta joins the Canadian company with a track record of experience across Mahana Therapeutics, Menlo Therapeutics, AlterG, Merz Aesthetics and BioForm Medical. Release

高管变更上市批准临床3期

2023-04-27

·PRNewswire

Antiva Biosciences Closes $53 Million Series E Equity Financing Led by MPM-BioImpact Capital and Names Kristine Ball President and CEO

Proceeds to Support Key Efficacy Studies for ABI-2280 including Phase 2 Trial in High-Grade Cervical Intraepithelial Neoplasia (CIN 2,3) and Exploratory Study as Treatment for High-Risk HPV Infections SOUTH SAN FRANCISCO, April 27, 2023 /PRNewswire/ -- Antiva Biosciences, a biopharmaceutical company developing novel, topical therapeutics for the treatment of pre-cancerous lesions caused by human papilloma virus (HPV) infection, today announced the closing of a $53 million Series E equity financing. The financing was supported by a syndicate of premier life science investors led by MPM-BioImpact Capital, and joined by the company's existing investors including Canaan Partners, Sofinnova Investments, Adjuvant Capital, GV and Lumira Ventures, among others. In conjunction with the financing, president and chief executive officer Gail Maderis is transitioning to chairman of the company's board of directors and is being succeeded as CEO by Kristine Ball. Additionally, Ms. Ball, along with Florencia Segal, M.D., and Brian Goodman, Ph.D., both of MPM-BioImpact Capital, will join the Antiva board. Proceeds from the financing, which will fund the company into late 2025, will support the advancement of the company's lead development candidate, ABI-2280, into key efficacy studies following completion of its ongoing Phase 1 trials. Planned studies include a Phase 2 clinical trial in high-grade cervical intraepithelial neoplasia (CIN 2,3) and an exploratory study as a potential treatment for high-risk HPV infection, specifically in subtypes that can lead to cancer. ABI-2280 has potent antiviral activity across all serotypes of HPV and works by both directly blocking HPV replication and inducing apoptosis in HPV-infected lesions, while sparing normal cells. Antiva has leveraged its development expertise to formulate a vaginal tablet of ABI-2280 that will enable self-administration at diagnosis and facilitate worldwide distribution, increasing impact potential for patients. The treatment of high-risk HPV infections with ABI-2280 holds the potential to address a significant global health challenge. HPV infections account for nearly all cases of cervical cancer around the world and an accessible and effective treatment holds the promise to dramatically reduce these cancers. Currently, there are no treatments available to resolve HPV infections and prevent their development into cancer. This remains a crucial unmet medical need with more than 5.5 million women in United States alone affected by high-risk HPV infections each year despite ready access to vaccines. "We believe that Antiva has the opportunity to make a transformative impact on global health across several large, unmet therapeutic indications with its ABI-2280 program and are thrilled to be able to lead this round of financing. The company has advanced the development of ABI-2280 to patients with CIN 2,3 and is now poised to expand clinical development into high-risk HPV infection. ABI-2280 can make the World Health Organization's screen-and-treat approach to HPV infection a reality," said Dr. Segal. Dr. Goodman added, "With MPM-BioImpact's growing focus on the field of virology, Antiva represents the type of impactful investment that we are looking to make in this space. We look forward to supporting Kristine in her new role as CEO and seeing the continued progress that is made under her leadership." Ms. Ball joins Antiva with more than 20 years of executive experience in the life sciences industry across companies of all stages ranging from discovery to clinical to commercial. She has significant transactional expertise, having participated in multiple initial public offerings, corporate M&A deals, partnerships and financings. Ms. Ball most recently served as chief executive officer of Soteria Biotherapeutics, a venture backed immuno-oncology company and previously held leadership positions at Menlo Therapeutics, Relypsa, Inc., and KAI Pharmaceuticals, and served on the board of Forty Seven, Inc., until its acquisition by Gilead. Ms. Ball currently sits on the board of Atreca, Inc., a publicly traded, clinical-stage oncology company. "I am deeply grateful for this opportunity to join Antiva at such an exciting time in the company's maturation. ABI-2280 has tremendous potential to play a significant role in advancing both global health and women's health, bringing about a long-needed breakthrough in HPV infections and HPV-related cancers in both men and women," stated Ms. Ball. "I am eager to carry forward the significant momentum that has been generated by the Antiva team and look forward to the important upcoming clinical development milestones that will move us closer to this goal. I am also excited to be able to work closely with Gail in her new role as board chair, leaning on the experience and knowledge she has gained during her time as president and CEO." "I take great pride in turning the CEO role over to Kristine with the company in such a strong position following this transformative financing. She is a talented and experienced life science executive who is perfectly suited to lead Antiva as it expands clinical development of ABI-2280," said Ms. Maderis. "I look forward to remaining intimately connected to the company in the role of board chair and offer a special thanks to Steve James, who has provided Antiva with great leadership and guidance as board chair and will remain an executive advisor to the company." About HPV-Related Diseases and Cervical Cancer Human Papilloma Virus (HPV) is so common that nearly all sexually active men and women are infected with the virus at some point in their lives. Many of these are transient infections the body is capable of clearing, but this typically takes months to years. When the infections persist, they are known to drive the formation of malignancies, including cervical, anal, vulvar, penile, and head and neck cancers. The introduction of prophylactic vaccines for HPV was a major step forward in the fight against HPV-associated cancers by preventing infection by certain high-risk HPV subtypes. However, due to low adoption rates in the US, EU, and Japan, and limited access to the vaccines in developing countries, HPV infections and the disease states driven by such infections remain a major unmet clinical need. Globally, cervical cancer is the fourth most common cancer in women and as such represents a major public health problem. According to the World Health Organization, an estimated 604,000 women were diagnosed with cervical cancer worldwide and approximately 342,000 women died from the disease in 2020. About Antiva Biosciences Antiva Biosciences, Inc. is a clinical-stage biopharmaceutical company developing novel, topical therapeutics for the treatment of diseases caused by HPV infection. The company, based in South San Francisco, was founded in 2012 by Dr. Karl Hostetler of The University of California San Diego. The company's lead drug candidate, ABI-2280 is being developed as a topical treatment for high-grade cervical intraepithelial neoplasia (HSIL, CIN 2,3) and for women with high-risk HPV infection. For more information, please visit: . Contact Information: Kristine Ball Antiva Biosciences, Inc. 650-822-1400 [email protected] Tim Brons Vida Strategic Partners (media) 646-319-8981 [email protected] SOURCE Antiva Biosciences, Inc.

临床2期高管变更疫苗并购

2023-03-10

·FierceBiotech

Vyne swings behind BET inhibitors, seeks partner for failed eczema drug

Vyne anticipates it has enough money to fund operations into the fourth quarter. Vyne Therapeutics is putting its mash-up of Pfizer’s Xeljanz and Novartis’ Gilenya on the back burner. After sifting through the data from a failed midphase eczema trial, the biotech has begun searching for a partner for the program to free up its own cash for development of its BET inhibitors. New Jersey-based Vyne, formerly known as Menlo Therapeutics, developed the topical combination of the approved drugs tofacitinib and fingolimod in the belief the combination of a JAK inhibitor and an S1P modulator would reduce inflammation from two different angles. However, the hypothesis took a hit last year when the formulation, FMX114, failed a phase 2a trial in mild to moderate atopic dermatitis. In response to the setback, Vyne outlined plans to reevaluate its pipeline and priorities. Initially, the firm made the case for FMX114, telling investors that additional analyses showed FMX114 was statistically superior to the control at weeks 1, 2 and 3. The problem was it failed to beat control at Week 4. Yet, in the months since that update, which made the case that FMX114 may be more effective in people with moderate to severe atopic dermatitis, Vyne has decided against committing more of its own cash to the program. Instead, the biotech is “evaluating partnering opportunities for this program” and putting its money into a pair of BET inhibitors. Vyne delivered phase 1a safety data on one of its BET inhibitors, the locally administered VYN201, last month. Initial results from a phase 1b trial of the candidate, which is in development as a treatment for vitiligo, are due around the middle of the year. Vyne’s second, oral BET inhibitor is in preclinical development for the treatment of immuno-inflammatory indications. The biotech has limited cash to commit to the programs. Having ended last year with $31 million in the bank, Vyne anticipates it has enough money to fund operations into the fourth quarter. Using FMX114 to land a deal could give Vyne some more money and buy it more time.