Image: Atomwise CEO and co-founder Abraham Heifets

Comment from

ESMO 2021: interim analysis backs Keytruda use in first-line cervical cancer therapy

Dr Judith M. Sills. Credit: Arriello

Dr Eric Caugant. Credit: Arriello

At the virtual annual European Society for Medical Oncology (ESMO) congress on 16-21 September, results from the Phase III KEYNOTE-826 study for Merck & Co’s programmed cell death protein (PD) 1 inhibitor, Keytruda (pembrolizumab), were presented, showing that both primary endpoints were met.

Adult patients with persistent, recurrent or metastatic cervical cancer, who were not previously treated with systemic chemotherapy, were randomised 1:1 to receive chemotherapy in combination with either Keytruda or placebo, with progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours v1.1 and overall survival (OS) being assessed by investigator review as dual primary endpoints.

Platinum-based chemotherapy in combination with Roche’s Avastin (bevacizumab) and paclitaxel is the current preferred treatment regimen for persistent, recurrent or metastatic cervical cancer, as established by results from the GOG 204 study, in which the median OS was 17.5 months.

In the Phase II KEYNOTE-158 study, Keytruda monotherapy demonstrated a 14.3% overall response rate in patients with programmed death-ligand (PD-L) 1-positive recurrent or metastatic cervical cancer who were previously treated with chemotherapy. The addition of PD-1 inhibition to chemotherapy with or without Avastin in first-line treatment had not yet been examined.

Table 1 indicates that the use of Keytruda and chemotherapy (with or without Avastin) significantly improved both PFS and OS in all three patient populations of the KEYNOTE-826 study.

Grade III or higher treatment-related adverse events were experienced by 81.1% of patients in the Keytruda arm and 75.1% of patients in the placebo arm, but by taking into account that the median durations of treatment were 10.0 and 7.7 months for the respective arms, Keytruda has a satisfactory safety profile.

Having met both dual primary endpoints, the KEYNOTE-826 trial will lead to broader therapeutic options and modify the treatment landscape for patients with persistent, recurrent or metastatic cervical cancer. Merck & Co believes that Keytruda and chemotherapy with or without Avastin can become the new standard of care in this setting.

The company may enjoy a large market share in the first-line segment for this setting, but Merck & Co could have stiff competition from a similar agent in the future.

Sanofi and Regeneron’s Libtayo (cemiplimab) versus chemotherapy significantly improved OS in the second-line treatment of cervical cancer in the Phase III EMPOWER-Cervical I trial, in which Libtayo reduced the risk of death by 31%, with a hazard ratio of 0.69.

Regeneron is expected to file a biologics license application to the US Food and Drug Administration in Q4 2021, but given Keytruda’s preliminary success, Regeneron may also decide to move Libtayo into first-line treatment in the future.

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02/24/2024 06:49:11

Image: Atomwise CEO and co-founder Abraham Heifets

COMMENT from

Unmet needs and opportunities for axillary hyperhidrosis

Dr Judith M. Sills. Credit: Arriello

Dr Eric Caugant. Credit: Arriello

The axillary hyperhidrosis (AH) therapeutics market has a considerable unmet need. GlobalData’s upcoming report, ‘Axillary Hyperhidrosis: Opportunity Assessment and Forecast to 2030,’ explores several key unmet needs in this disease space

This includes improved anticholinergic drug delivery systems, therapies causing longer-lasting neuromuscular blockade, increased awareness and education and better insurance coverage for treatments.

Improved anticholinergic delivery systems

Journey Medical Corporation’s Qbrexza (glycopyrronium tosylate), a topical anticholinergic drug, was approved by the US Food and Drug Administration (FDA) in 2018 and has become a game-changer in the AH treatment paradigm.

Before Qbrexza’s approval, antiperspirants were the only choice of therapy. Qbrexza wipes are easy to use with few side effects, resulting in rapid acceptance of the medication by patients and improved adherence. Currently, Brickell Biotech’s Ecclock (sofpironium bromide) is the only anticholinergic pipeline agent in Phase III development.

Despite having superior efficacy to Qbrexza, Ecclock gel does not offer a better delivery method, particularly one that minimizes hand contact with the drug. This is a major opportunity remaining for drug developers in this space.

Longer-lasting neuromuscular blockade

After failing to respond or losing response to antiperspirants and topical anticholinergics, patients with AH are eligible to receive neuromuscular blockade via local botulinum toxin injection.

The only marketed drug in this class that is approved for use in AH is AbbVie’s Botox (onabotulinumtoxin A). However, with only four to six months duration of action (based on the severity of the AH), botulinum toxin therapies present only a temporary solution to symptoms.

Currently, there is an absence of pipeline agents in the neuromuscular blockade drug class. Therefore, the opportunity remains for drug developers to investigate an alternative neurotoxin drug that requires less frequent injection than Botox.

Increased awareness and education

The negative impacts of AH on social functioning are often underestimated. KOLs noted that despite the availability of treatments that can effectively control sweating and improve patients’ quality of life, the majority of patients remain undiagnosed and do not seek treatment.

As such, there remains a significant need for greater investment into educational strategies to increase awareness about AH and the types of treatments that are currently available. This will help to increase the diagnosis rate and hopefully bring significant quality-of-life improvements to the AH patient population.

Improved insurance coverage

Generally, health insurance coverage for AH treatment in the US is limited to patients who meet certain requirements. Regardless of severity, patients must receive prescription antiperspirants as first-line therapy to be able to receive topical anticholinergics as second-line therapy.

In addition, insurance coverage only applies to medications and not to procedures such as microwave energy treatment, miraDry, or surgeries. Therefore, better strategies are needed to improve insurance coverage.

GlobalData believes that the lack of late-stage pipeline products for AH and other unmet needs represent important opportunities for pharmaceutical and biotechnology companies to transform the treatment paradigm for affected patients.

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02/23/2024 22:12:55