Alpha-1 Antitrypsin Deficiency

A hereditary enzyme deficiency caused by SERPINA1 mutations, producing progressive emphysema, COPD, and liver disease due to insufficient circulating alpha-1 antitrypsin. Approximately 90% of genetically confirmed USA patients remain undiagnosed.

About Alpha-1 Antitrypsin Deficiency

In numbers

Pi*ZZ genotype (most severe) affects approximately 1 in 2,500–5,000 Northern Europeans; an estimated 80,000–120,000 individuals in the USA are affected.
Only 5–10% of USA Pi*ZZ individuals are formally diagnosed — leaving approximately 70,000–100,000 patients undetected and untreated.
Pi*MZ carriers (~3–4% of Northern European populations) carry significantly elevated disease risk that is largely unrecognised in current care pathways.

Special details

Highest Pi*ZZ prevalence occurs in Northern European populations; significant rates are documented in Southern European, Middle Eastern, and other ancestries.
Volv Global’s real-world data project revealed the true AATD population is younger and more ethnically diverse than current coded diagnoses indicate.
Cascade genetic testing following one confirmed AATD diagnosis routinely identifies multiple previously undiagnosed relatives, multiplying the impact of each detected case.

Signs and symptoms of Alpha-1 Antitrypsin Deficiency

Diagnostic delay averages 5–10 years from first respiratory symptom to confirmed diagnosis. Fewer than 0.2% of US COPD patients have been tested for AATD — leaving an estimated 90% of genetically affected individuals undiagnosed.

Progressive dyspnoea on exertion

Progressive dyspnoea on exertion appearing 20–30 years earlier than expected for typical COPD, frequently attributed to asthma in initial clinical encounters.

Basal-predominant panacinar emphysema on HRCT imaging

A pattern distinct from smoking-related upper-lobe emphysema, but routinely missed without specific AAT testing.

Recurrent lower respiratory tract

Recurrent lower respiratory tract infections and unexplained airflow obstruction, particularly in young adults who have never or minimally smoked.

Liver disease

Elevated transaminases, cirrhosis, or hepatocellular carcinoma — especially in young adults without conventional hepatic risk factors.

Necrotising panniculitis and ANCA-associated

Necrotising panniculitis and ANCA-associated vasculitis appear in a minority of patients, extending the diagnostic journey beyond pulmonary medicine.

Key challenges from product development to launch

Strategy and Business

The wrong disease or indication selected for investment
Indications tackled in the wrong order due to shaky success estimates
R&D returns slipping below the cost of capital

Clinical Development

Trials delayed by low patient recruitment
High screen-failure rates that raise trial cost
Mixed cohorts that make the signals difficult to detect

HEOR, Access & Value

A value case that arrives too late or is underdeveloped
Eligible population under-counted, budget-impact case unsubstantiated
Approved by the regulator, delayed at HTA

Medical Affairs

Fragmented, differently-coded healthcare data
Diagnostic delay that is long and unequal
No shared evidence base across functions

Launch and Commercial

Launch planned without a view of the number of findable patients
Targeting too broad a population slows early uptake
RWE started too late to build the case

How Volv Global Helps

Strategy and Business

Pipeline mistakes compound from the earliest decisions: wrong indication, indications tackled in the wrong order, capital deployed where returns already trail the cost of capital.

inTrigue

Finds the true reachable population per candidate, so indication choices rest on evidence.

volv.global/finding-patients

inFlow

Adds probability-of-success and outcome evidence to help prioritise the pipeline.

volv.global/predict-patient-outcomes

Clinical Development

When patients cannot be found, recruitment stalls and the burn rate climbs. High screen failure rates add to the drain, and a mixed cohort makes the results harder to interpret.

inTrigue

Finds the undiagnosed and mis-coded patients conventional feasibility misses, widening the recruitable pool.

volv.global/finding-patients

inCare

Surfaces diagnosed-but-hidden, trial-eligible patients already in the data, so sites enrol faster.

volv.global/stratifying-patient-cohorts

inFlow

Predicts who will progress or respond, enriching the cohort so the signal is not diluted.

volv.global/predict-patient-outcomes

HEOR, Access & Value

Thin or late evidence lets payers restrict access or cut the price. A poorly sized population exposes the budget case, and HTA demands more than the regulator.

inFlow

Generates the real-world evidence and outcomes payers ask for, ahead of the submission deadline.

volv.global/predict-patient-outcomes

inTrigue

Finds the undiagnosed patients missing from the count, so the eligible population holds up under scrutiny.

volv.global/finding-patients

inCare

Surfaces the diagnosed-but-eligible patients who expand the eligible population count.

volv.global/stratifying-patient-cohorts

Medical Affairs

Fragmented data must be built market by market, slowing decisions. Time to correct diagnosis varies by who the patient is and where they receive care.

inTrigue

Works across fragmented, differently-coded data by design, so insight holds up country to country without a rebuild.

volv.global/finding-patients

inAdvance

Detects patients ahead of typical diagnosis, closing the gap in awareness and pathway that drives unequal delay.

volv.global/earlier-detection

Launch and Commercial

A launch without a view of findable patients is poorly resourced from day one. Targeting too broad a population slows early uptake, and late real-world evidence means the access dossier goes in rushed.