GSK Sets Up Late-Stage Readouts: Chronic Cough Phase 3 Data Near, Hep B Filing on Track

28 Mar 2026, 02:03 by Danessa Lincoln · The Markets Daily

GSK (NYSE:GSK) respiratory, immunology and inflammation R&D head Kaivan Khavandi said the company is positioning several late-stage programs around clear unmet need and what he described as better “target trait pairing,” highlighting upcoming chronic cough data, planned hepatitis B regulatory steps, and recent business development that focuses on validated biology with room for differentiation.

Chronic cough: “debilitating” prevalence and a focus on benefit-risk

Khavandi described refractory chronic cough as a large and underserved condition, citing an estimated prevalence of about 40 million globally. He said the disease can be incompatible with normal daily life, with some patients experiencing “100 coughs an hour,” and noted consequences including incontinence and rib fractures. He added that patients recruited into GSK’s program have tried treatments such as opioids and neuropathic medications, underscoring demand for a safe, effective therapy.

Discussing GSK’s P2X3 antagonist camlipixant and expected Phase 3 readouts later this year, Khavandi said Merck’s gefapixant “de-risks the efficacy of the pathway,” but argued that gefapixant’s lack of selectivity led to problematic taste disturbance that hurt its overall benefit-risk profile in the U.S. He said a placebo-adjusted reduction in 24-hour cough frequency on the order of 15% is considered clinically important, particularly in an enriched population with high baseline cough burden.

Khavandi also addressed why Phase 2 placebo-adjusted effects may appear larger than Phase 3 results, pointing to a pattern seen in analogous conditions such as pain, IBS, and migraine where placebo-adjusted efficacy can be discounted in longer pivotal trials. He said change-from-baseline effects may be similar, but pivotal “operating characteristics” influence placebo-adjusted outcomes.

CALM-1 and CALM-2: enrichment, patient-reported outcomes, and endpoints

Khavandi said the CALM-1 and CALM-2 Phase 3 trials were initiated by Bellus and staggered, which is why they are not reading out simultaneously. He said CALM-1 has completed, while CALM-2 has completed enrollment; he added that CALM-2 remains listed as open on clinicaltrials.gov because of the long-term extension.

After GSK took over the studies, the company increased sample size, which Khavandi attributed to two factors:

Patient-reported outcomes: Following the gefapixant advisory committee, GSK anticipated the FDA would want patient-reported outcome data using an appropriate instrument. Khavandi said GSK introduced the Chronic Cough Diary as a key secondary endpoint and powered to evaluate it alongside 24-hour cough frequency.
Enrollment enrichment: GSK agreed with the FDA to enrich enrollment 3-to-1 for patients with more than 20 coughs per hour at baseline (versus those with 8 to 20), and increased sample size accordingly.

Khavandi said the enrichment approach applies to both CALM-1 and CALM-2. He explained that the two trials have different primary endpoint timing—cough frequency at week 12 for CALM-1 and week 24 for CALM-2—based on what was agreed with the FDA in Phase 2, with the longer endpoint supporting durability and safety data.

On tolerability and trial integrity, Khavandi said gefapixant’s high rate of taste disturbance (he cited over 50% and “over 60%”) could compromise blinding. By contrast, he said camlipixant’s taste disturbance signal in blinded data is low and that GSK expects “almost no” discontinuations driven by taste issues, indicating a level “7% or less,” and potentially lower, based on substantially greater selectivity.

Khavandi said placebo response is expected in this setting, but noted GSK used a placebo run-in and could exclude patients with an exaggerated placebo response—steps he said gefapixant’s program did not include.

Bepirovirsen: FDA filing timing and why 15% functional cure matters

Turning to bepirovirsen for chronic hepatitis B, Khavandi said GSK remained on track regarding its planned FDA submission timing. While he did not state that the filing had been completed, he said the company would typically disclose progress when it receives acceptance to file and is “on track to disclose acceptance to file within Q1.” He also said full data are expected to be presented at EASL.

Khavandi discussed why a 15% functional cure rate would be clinically meaningful, defining the bar as undetectable hepatitis B surface antigen six months after stopping all treatments, including nucleoside analogs. He said this endpoint is an “ambitious” definition of cure and tied it to improved outcomes, citing a “70% reduction” in likelihood of hard endpoints related to malignancy and mortality. For context, he said nucleoside analogs achieve functional cure rates of less than 1% against that endpoint in controlled trial settings.

Khavandi added that durability would be a key consideration, noting the study design allows assessment of sustained response and that some patients enter long-term follow-up.

On commercial potential, he said uptake and market development may vary by geography. He characterized the currently diagnosed population as skewed toward markets such as the U.S., which he said are “ready to go,” and described low- and middle-income countries as areas where effective therapeutics could drive expanded diagnosis. He said GSK’s view of geographic contribution is “fairly representative” between markets like the U.S. and China.

Deal strategy: validated mechanisms with “white space” for differentiation

Khavandi said business development reports into R&D at GSK and described a process in which R&D category strategies inform search and evaluation, followed by triage against criteria including translational confidence, unmet need, market proposition, and development tractability.

He also argued that the “first-in-class” and “best-in-class” framing is increasingly challenged, saying fast followers can quickly emerge and that “best in class” depends on factors like the right indication and population. He said GSK aims to “bag the validated biology” to reduce risk while differentiating through population selection and responder phenotypes.

RAPT food allergy and FGF21 in MASH: administration burden and clinical positioning

Discussing GSK’s RAPT deal in food allergy, Khavandi said IgE biology has been validated and cited Xolair’s early commercial success in food allergy as evidence of unmet need, given what he described as primitive standard of care centered on avoidance and carrying epinephrine for anaphylaxis. He argued that the two-weekly administration pattern seen in market data is burdensome, especially in pediatrics and adolescents, and highlighted complexity in Xolair dosing that relies on a nomogram based on IgE levels and weight.

Khavandi said IgE accounts for about 95% of food allergies and described IgE monoclonal antibodies as allergen-agnostic compared with allergen-specific oral immunotherapies. He said RAPT’s trial mandates patients have two or more food allergens. Addressing concerns about long-term IgE blockade in children, he pointed to Xolair’s long history in pediatric asthma and said he has seen no data suggesting cause for concern.

On the FGF21 class and GSK’s efimosfermin deal, Khavandi said the class has shown histopathological reversal of cirrhosis—something he said was considered unachievable five years ago—and could represent a “step change” in efficacy in F2/F3 MASH and potentially cirrhotic MASH and alcohol-related liver disease. He said GSK evaluated efimosfermin based on immunogenicity and anti-drug antibody considerations, scalability and cost of goods, and what he described as potential advantages in time of onset and durability. He also emphasized the burden of comorbidities and polypharmacy in metabolic syndrome and said injection frequency matters for adherence.

Asked about GLP-1s, Khavandi said they are effective at MASH resolution but less effective at fibrosis improvement in F2/F3 and “ineffective in cirrhotic MASH,” adding that GLP-1s have shown an unfavorable effect versus placebo in cirrhotic MASH. He said efimosfermin trials permit GLP-1 background therapy and that FGF21 efficacy is preserved on top of GLP-1s, framing FGF21 therapies as more likely to be used when patients move from primary care into specialist hepatology settings.

Khavandi also said GSK is applying AI across medicine design and oligonucleotide sequencing, but described the “next frontier” as using AI to reason over complex biology and multimodal human datasets. He said GSK has built datasets spanning proteomics, genetics, transcriptomics, spatial transcriptomics, imaging, and clinical endpoints, and cited this approach as supporting conviction around IL-33 and TSLP combination therapeutic strategies.

About GSK (NYSE:GSK)

GSK (GlaxoSmithKline plc) is a London-headquartered, multinational pharmaceutical and healthcare company formed through the 2000 merger of Glaxo Wellcome and SmithKline Beecham. The company is dual-listed and operates globally, developing, manufacturing and commercializing prescription medicines, vaccines and specialty treatments. Over its history GSK has evolved through portfolio reshaping and strategic transactions to focus on science-led pharmaceuticals and vaccines.

GSK’s core activities include research and development of therapies and vaccines across a range of therapeutic areas, commercial manufacturing, and global marketing.