Emicizumab for Severe Von Willebrand Disease (VWD) and VWD/Hemophilia A

Inclusion Criteria:

• Signed informed consent

• Age 0 and older (infants weighing ≥3 kg)

• ability to comply with protocol in investigators judgement

• diagnosis of: severe VWD type 3, or VWD with VWF antigen, activity or collagenbinding </= 20 U/dl or variant VWD confirmed by genetic mutation and VWF ag,activity or CB < 50 U/dl based on historical medical records of study site.

• diagnosis of VWD/hemophilia A defined as VWF:ag, activity or CB <50 U/dl, and mildmoderate or severe hemophilia A(defined by ISTH criteria) based on historicalmedical records of the study site.

• plan to be adherent to emicizumab prophylaxis during the study

• Patient's bleeding phenotype necessitating prophylaxis per treating providerrecommendations.

• Patient on current prophylaxis for VWD or VWD/hemophilia A may enroll if they arecurrently on a non-emicizumab agent, and if it has been > 18 months since lastoff-label dose of emicizumab, and are willing to discontinue current prophylaxis.

• For menstruating individuals: agreement to remain abstinent (refrain fromheterosexual intercourse) or use contraceptive methods that result in a failure rateof < 1% per year during the study period. A menstruating individual is considered tobe of childbearing potential if they are post-menarchal, have not reached apostmenopausal state (12 continuous months of amenorrhea with no identified causeother than menopause), and have not undergone surgical sterilization (removal ofovaries and/or uterus).

Examples of highly effective contraceptive methods with a failure rate of < 1% per year include proper use of combined oral or injected hormonal contraceptive, bilateral tubal ligation, male sterilization, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

• Patients and/or infants weighing < 3 kg.

• Patients with low VWF or non-severe VWD (ie.not meeting the above criteria)

• Other concomitant bleeding disorders including coagulopathy from liver cirrhosis.

• Current treatment with emicizumab or emicizumab therapy in the previous 18 months.

• Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for whichanti-thrombotic treatment is not currently ongoing) or current signs ofthromboembolic disease

• Other conditions (e.g., certain autoimmune diseases, including, but not limited todiseases such as systemic lupus erythematosus, inflammatory bowel disease, andantiphospholipid syndrome) that may increase the risk of bleeding or thrombosis

• Patients who are at high risk for thrombotic microangiopathy (TMA; e.g., have aprevious medical or family history of TMA), in the investigator's judgment

• Would refuse treatment with blood or blood products, if necessary.

• Any serious medical condition or abnormality in clinical laboratory tests that, inthe investigator's judgment, precludes the patient's safe participation in andcompletion of the study

• Treatment with any of the following:

An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration before Study Day 1 A non-hemophilia-related investigational drug within the last 30 days or 5 halflives- before Study Day 1, whichever is longer An investigational drug concurrently

• History of clinically significant hypersensitivity associated with monoclonalantibody therapies or components of the emicizumab injection

• Pregnant or lactating, or intending to become pregnant during the study

• Women of childbearing potential must have a negative serum pregnancy test resultwithin 7 days before Study Day 1

• Illicit drug or alcohol abuse within 12 months prior to screening, in theinvestigator's judgment

• Serious infection requiring oral or IV antibiotics within 30 days prior to screening