UP FRONT
Pulling Back the Curtain : Eduardo Sotomayor , MD
faculty have so much energy and are brimming with ideas – they want to conquer the world ! I was in their shoes many years ago and now I am happy to be able to support them in the fight against cancer .
What is one thing people would be surprised to learn about you ? People might be surprised to learn that I was shy growing up . I didn ’ t want to ask questions ; I preferred to just listen . Now I think that people would say I ’ m engaging , so I don ’ t know what happened . I would still say that I enjoy being a supporting actor rather than the star . It ’ s interesting though , because life has tended to push me in the direction of taking more of a central role . However , what I enjoy most about being the director of a cancer center is putting people together to attack a problem , whether immunologists , engineers , clinicians , surgeons , social
ADYNOVATE ® [ Antihemophilic Factor ( Recombinant ), PEGylated ] Lyophilized Powder for Solution For Intravenous Injection Brief Summary of Prescribing Information : Please see package insert for full Prescribing Information .
workers , computational scientists , or anthropologists – anyone who can help .
What do you do in your off hours ? Like I mentioned earlier , my interest in politics and policy has never left me . And , I have recently become a wine collector . I was introduced to wine collecting when I was at Moffitt , where several faculty were already in the habit of collecting wines . Then that interest turned into taking trips
with my wife , Maria , to Napa Valley and buying wines to enjoy with friends and family . That passion has now extended to food . When Maria and I travel , we enjoy seeking out new restaurants .
We have been married for 27 years . We met in medical school in Lima and she is now a dermatologist practicing at GWU . We have two children : Mariana , who works at NBC News here in Washington , DC , and Eduardo Jr ., who is a sophomore at New York University . It is too early for him to decide what he wants to do , but he is interested in art business . I just want him to be passionate about whatever he does .
INDICATIONS AND USAGE
ADYNOVATE , Antihemophilic Factor ( Recombinant ), PEGylated , is a human antihemophilic factor indicated in children and adults with hemophilia A ( congenital factor VIII deficiency ) for :
• On-demand treatment and control of bleeding episodes
• Perioperative management
• Routine prophylaxis to reduce the frequency of bleeding episodes
Limitation of Use ADYNOVATE is not indicated for the treatment of von Willebrand disease . CONTRAINDICATIONS
ADYNOVATE is contraindicated in patients who have had prior anaphylactic reaction to ADYNOVATE , to the parent molecule ADVATE ® ( Antihemophilic Factor [ Recombinant ]), mouse or hamster protein , or excipients of ADYNOVATE ( e . g . Tris , mannitol , trehalose , glutathione , and / or polysorbate 80 ).
WARNINGS AND PRECAUTIONS Hypersensitivity Reactions
Hypersensitivity reactions are possible with ADYNOVATE . Allergic-type hypersensitivity reactions , including anaphylaxis , have been reported with other recombinant antihemophilic factor VIII products , including the parent molecule , ADVATE . Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema , chest tightness , dyspnea , wheezing , urticaria , and pruritus . Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur .
Neutralizing Antibodies
Formation of neutralizing antibodies ( inhibitors ) to factor VIII can occur following administration of ADYNOVATE . Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests . Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected , or if bleeding is not controlled with expected dose .
Monitoring Laboratory Tests
• Monitor plasma factor VIII activity by performing a validated one-stage clotting assay to confirm the adequate factor VIII levels have been achieved and maintained .
• Monitor for the development of factor VIII inhibitors . Perform the Bethesda inhibitor assay to determine if factor VIII inhibitor is present . If expected factor VIII activity plasma levels are not attained , or if bleeding is not controlled with the expected dose of ADYNOVATE , use Bethesda Units ( BU ) to determine inhibitor levels .
ADVERSE REACTIONS The most common adverse reactions ( ≥1 % of subjects ) reported in the clinical studies were headache and nausea .
Clinical Trials Experience Because clinical trials are conducted under widely varying conditions , adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice .
The safety of ADYNOVATE was evaluated in 237 previously treated patients ( PTPs ) and 6 previously untreated patients ( PUPs ) with severe hemophilia A ( factor VIII less than 1 % of normal ), who received at least one dose of ADYNOVATE in 3 completed multicenter , prospective , open label clinical studies and 4 ongoing clinical studies . The median duration of participation per subject was 401 ( min-max : 3-1034 ) days and the median number of exposure days to ADYNOVATE per subject was 111 ( min-max : 1-322 ). Table 1 lists the adverse reactions reported during clinical studies .
Table 1 : Adverse Reactions Reported for ADYNOVATE
MedDRA System Organ Class
Gastrointestinal Disorders Immune System Disorder Nervous System Disorders Skin and Subcutaneous Tissue Disorders Vascular Disorders
MedDRA Preferred Term
Number of Subjects n (%) ( N = 234 )
Rate of AEs per 100 Infusions ( N = 30865 )
Diarrhea |
1 ( 0.4 %) |
0.003 |
Nausea |
2 ( 0.8 %) |
0.006 |
Hypersensitivity a 1 ( 0.4 %) 0.003
Headache 5 ( 2.1 %) 0.026 Rash 1 ( 0.4 %) 0.003 Flushing 1 ( 0.4 %) 0.003 a
The event of hypersensitivity was a mild transient non-serious rash , occurring in one 2-year old patient who had developed a previous rash while on ADYNOVATE .
Two cases of acute pancreatitis , with no precipitating cause identified in one case , were reported in adults during an extension study of the clinical trial which evaluated 137 subjects . Administration of ADYNOVATE continued and both cases resolved .
Immunogenicity
The risk of the development of factor VIII inhibitors with the use of ADYNOVATE was evaluated in 3 completed and 4 ongoing clinical trials . Subjects consisted of adolescent and adult ( n = 148 with ≥150 prior EDs ) and pediatric PTPs [(< 6 years of age with ≥50 prior EDs ( n = 32 ), ≥6 years of age with ≥150 prior EDs ( n = 57 )], and pediatric PUPs ( n = 6 ). In 191 adult and pediatric PTPs who were treated for at least 50 exposure days with ADYNOVATE , the factor VIII inhibitor frequency was 0 ( 95 % CI of 0 to 0.019 ). One PUP subject from an ongoing study , who received at least one infusion of ADYNOVATE , developed neutralizing antibodies to factor VIII .
Immunogenicity also was evaluated by measuring the development of binding IgG and IgM antibodies against factor VIII , PEGylated ( PEG ) -factor VIII , PEG and Chinese hamster ovary ( CHO ) protein using validated ELISA assays . The majority of subjects ( 238 / 243 ) with at least one infusion of ADYNOVATE did not develop a persistent binding antibody response to any of these antigens . Twenty-eight subjects in total showed pre-existing antibodies to factor VIII ( n = 3 ), PEG-factor VIII ( n = 25 ) and / or PEG ( n = 3 ) prior to the first exposure to ADYNOVATE . Thirteen subjects who tested negative at screening developed transient antibodies against factor VIII ( n = 6 ), or PEG-FVIII ( n = 8 ) at one or two consecutive study visits . Antibodies were transient and not detectable at subsequent visits . Five subjects showed positive results for binding antibodies at study completion or at the time of data cutoff . Binding antibodies that were detected prior to exposure to ADYNOVATE , that transiently developed during the trial or were still detectable at study completion or data cutoff could not be correlated to any impaired treatment efficacy or altered PK parameters . There was no causal relationship between observed adverse events and binding antibodies except in one subject where a causal relationship cannot be ruled out based on available data . No subject had pre-existing or treatment-emergent antibodies to CHO protein .
The detection of antibodies that are reactive to factor VIII is highly dependent on many factors , including : the sensitivity and specificity of the assay , sample handling , timing of sample collection , concomitant medications and underlying disease . For these reasons , comparison of the incidence of antibodies to ADYNOVATE with the incidence of antibodies to other products may be misleading .
Baxalta , Advate , Adynovate , and Baxject are trademarks of Baxalta Incorporated , a wholly owned , indirect subsidiary of Shire plc .
Baxalta US Inc . Westlake Village , CA 91362 USA U . S . License No . 2020 Issued 12 / 2016 16I045-ADY-US S24588 01 / 17
Drs . Sotomayor at Granada Cathedral in Spain .
If you could have dinner with one person from history , who would it be ? I would love to speak with William Coley , a pioneer of cancer research and immunotherapy . In 1891 , he produced the first cancer vaccine by injecting bacteria into a patient with a sarcoma tumor . He was so far ahead of his time , and his contemporaries might have rejected his ideas , but this marked the beginning of cancer immunotherapy .
I would love to show him how far the field of immunotherapy has come , to the point where we are now using immunotherapy to successfully treat several types of cancers . And I would love to know his thoughts after seeing his ideas becoming a reality almost 120 years later . It would be an incredible conversation . ●
June 2017