Eliapixant

Pictured: Exterior of an FDA building/iStock, Grandbrothers Merck’s drug to treat chronic cough, the P2X3 receptor antagonist gefapixant, is facing some concerns about its effectiveness from the FDA ahead of Friday’s advisory committee meeting. According to the FDA’s briefing document, the agency’s assessment of the data that has been submitted by Merck is that gefapixant “showed a small reduction in cough frequency” while uncertainty remains as to “whether the effect is clinically meaningful.” Merck’s briefing document makes the case for a clinically meaningful reduction in cough frequency in patients, emphasizing that the drug’s efficacy claim is based on two Phase III trials that looked at gefapixant in adults. The primary endpoint was the reduction of 24-hour cough frequency, as measured by the VitaloJAK cough counting system. Merck maintains that both studies met the primary endpoint criteria. Those with a 45-mg dose had a reduction of 18.45%, a p-value of p=0.041% at week 12, and a 14.64% reduction at week 24, earning a p-value of p=0.031. The 15-mg section did not “differentiate” from the placebo, according to the company. “Based on this result, the proposed dosing regimen is gefapixant 45 mg [twice daily] (and the results presented in this document largely focus on this regimen),” according to Merck. However, the FDA document notes that disturbance or loss of taste occurred in up to 65% of participants taking the drug, while around 14% of patients had discontinued the trial. “With a large placebo response and wide range of cough frequencies at baseline, we question if the small treatment difference in cough frequency is noticeable to patients. What constitutes a meaningful reduction in cough frequency is not established; therefore, we ask the Committee to consider whether the change in cough frequency with gefapixant will be perceptible and meaningful to patients,” the FDA said in its briefing document. Gefapixant has had a rough path in the regulatory approval process. After the drug’s NDA was accepted to be reviewed by the FDA in 2021, it encountered a speed bump a year later. In January 2022, the regulator issued a Complete Response Letter to Merck. While the company did not explain why the CRL was handed down, safety issues were not the cause and Merck said it remained “committed” to advancing the drug. Friday’s adcomm meeting for gefapixant comes as competition is bearing down on Merck in the chronic cough treatment arena. In April 2023, GSK inked a $2 billion deal to acquire Canadian biotech Bellus Health, gaining access to its chronic cough candidate camlipixant. That drug is also an antagonist of the P2X3 receptor and had met its primary endpoint in a 2021 clinical trial. Meanwhile, Bayer jumped out of the chronic cough space last year, abandoning Phase II development of eliapixant, which was being developed for chronic cough and endometriosis, diabetic neuropathic pain and overactive bladder. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

TORONTO, May 03, 2023 (GLOBE NEWSWIRE) -- Dalriada, a leading Canadian contract research organization specializing in small molecule therapies, announces today that it has strengthened its executive leadership team, appointing Adam Davenport, Ph.D. as its Chief Research & Development Officer (CRDO). Dr. Davenport joins from Evotec and will assume strategic and scientific execution responsibility for all of Dalriada’s programs, as well as its current and future R&D capabilities. Serving most recently as Head of Global Molecular Discovery at Evotec where he spent his whole career, Dr. Davenport is a seasoned drug discovery leader and innovator who brings over 22 years of hands-on life science and partnership organization experience, having contributed to drug candidates and clinical assets through both governance and scientific leadership roles. Dr. Davenport has a strong track record of progressing multiple projects through Discovery into Clinical evaluation and is lead inventor of P2X3R antagonists Eliapixant and Filopixant, achieving Phase 2a PoCs in Persistent Chronic Cough (PCC), and Bradykinin B1R antagonist Fulimetibant, undergoing a Phase 2a study to treat diabetic neuropathic pain (DNP). His expertise spans across modalities, diverse target classes (GPCRs, ion-channels, PPIs, CNS, kinases, enzymes) and therapeutic areas (pain, inflammation, cognition, metabolic, Women’s Health, and respiratory). “I am thrilled to welcome Dr. Davenport to Dalriada as its new CRDO,” said Dr. Diana Kraskouskaya, Dalriada’s CEO and co-founder. “Throughout his outstanding career at Evotec, Dr. Davenport has been at the forefront of drug discovery. He is a renowned chemist and authority in his area of expertise, and we believe his addition to the team will further strengthen our strategies and capabilities, as we strive to become the partner of choice for our biotech partners and clients,” she added. Dalriada’s co-founder & CSO Prof. Patrick Gunning added: “At Dalriada we look forward to leveraging Dr. Davenport’s vast experience and insights gained from over 20 years spent at Evotec, and we are excited that our team and clients will benefit from his expertise in a wide range of modalities and disease areas.” Dr. Davenport commented on his appointment: “I am delighted to join Dalriada, a company purposely built as an agile, co-located, and integrated drug discovery partner, which pioneers its unique TURN-KEYTM model to accelerate the discovery and development journey of high value small molecule therapeutics from concept to IND.” “The company is at the forefront of covalent and other novel small molecule modality drug discovery and combining this with its TURN-KEYTM operational model, provides the flexibility, creativity, and innovation that the biotech and VC sectors need to drive value creation and return on investment.” “As a veteran of the CRO world, I have been hugely impressed by the passion, knowledge, drive, and entrepreneurial spirit of Dalriada’s leadership team. I look forward to working alongside them to collectively make a difference for patients, by strategically leading the Company’s R&D.” Dr. Davenport will be based out of Dalriada’s UK site, as part of the Company’s growing presence in Europe, focusing on project strategy and leadership. A detailed biography for Dr. Davenport is available at www.dalriadatx.com/about/adam-davenport/ About Dalriada Drug Discovery Inc. Dalriada, through its TURN-KEY™ Drug Discovery services model, provides a full suite of drug discovery, medicinal chemistry and intellectual property services for semi-virtual, lean biotechnology clients who focus on developing small molecule therapies. With R&D operations in Mississauga, Canada, Dalriada builds focused teams with expertise in MedChem, Biology and ADME to allow for the most rapid and cost-effective project execution and value building. Dalriada has niche expertise in several areas including covalent drug discovery, GPCR programs, targeted protein degradation, novel hetero-bifunctional modalities and CNS programs, with proprietary screening platforms in several of these areas. About Dalriada’s TURN-KEY model TURN-KEYTM provides a powerful one-stop alternative to the prevailing CRO models, fulfilling the most common needs of small to medium-size biotech companies. Via its three key operational pillars of Discovery Labs, Discovery Strategy and Discovery Management, the model reduces the costs of internal R&D and G&A, shortens the timelines to reaching value inflection points, and removes the burden of managing a network of sub-contractors. Our partners instantaneously tap into deep expertise in small molecule discovery (including a curated network of global Key Opinion Leaders), agile execution in integrated lab, and subcontracting and project management teams. The model is fundamentally based on agility, collaborative approach, focus on building value, expert input, and quality execution. A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/0dc99ed0-3885-4f79-9b33-12e7d9c075ae