Molecular Therapy for SMA in Clinical Practice 2019 - American ...
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2019
Molecular Therapy for SMA in
Clinical Practice
2019 Introduction Professor of Clinical Pediatrics and Neurology Assistant Professor of Pediatrics, Neurology and at the University of Colorado Neurotherapeutics at the University of Texas Haberfeld Family Endowed Chair in Pediatric Southwestern in Dallas Neuromuscular Disorders Co-Director, Neuromuscular Clinic Co-Director, Neuromuscular Clinic
2019 Program Overview Contact Start Time Duration Title Castro, Diana 10/19/2019 8:00 5 Introduction Castro, Diana 10/19/2019 8:05 25 Molecular basis of SMA Castro, Diana 10/19/2019 8:30 25 Current Therapies and research for SMA Parsons, Julie 10/19/2019 8:55 25 Complex Drug Program: One model Discussion and Q & A 10/19/2019 9:20 10 Discussion and Q & A
2019
Molecular Basis for Spinal
Muscular Atrophy
Diana Castro, MD
Assistant Professor of Pediatrics, Neurology and Neurotherapeutics
University of Texas Southwestern Dallas
2019 Financial Disclosure Research Support and/or Advisory Board • Biogen Pharmaceutical • Avexis/Novartis • Sarepta Pharmaceutical • PTC Therapeutics • Fibrogen • ReveraGen • CINRG • Muscular Dystrophy Association • National Institute of Health • Guillain-Barre Syndrome/CIDP Foundation • Cure SMA
2019 Warning Videotaping or taking pictures of the slides associated with this presentation is prohibited. The information on the slides is copyrighted and cannot be used without permission and author attribution.
2019
Spinal Muscular Atrophy (SMA)
• Group of disorders that affect the lower motor neuron 5qSMA
• Caused by different genes Recessive SMA
(Survival Motor
Neuron)
Proximal
Non 5qSMA
Recessive
Dominant
SMA X-Linked (recessive)
Recessive
Dominant
Distal X-linked
Mitochondrial
Sporadic
2019
SMN Gene
SMA Region
Outline
SMN Protein and Functions
2019 Survival Motor Neuron Gene (SMN) • Chromosome 5q • SMN gene is duplicated in humans • SMN1 and SMN2 genes lie on a large, inverted duplication on chromosome 5q13 • The SMN1 gene lies within the telomeric halve • The SMN2 gene lies within the centromeric halve
2019
Arrangement of Genes in the
SMA region The gene can be arranged in a tandem
duplication or with genes absent from one
of the repeat units.
• SERF1, small EDRK-rich factor
• SMN1, survival motor neuron 1
• NAIP, Neuronal apoptosis inhibitory protein
• BTF2p44, basic transcription factor 2 44-
kDasubunit
Burges, A, McGovern, V. Genetics of Spinal Muscular Atrophy. Molecular and Cellular Therapies for Motor Neuron Diseases.2019
SMN Gene
The SMN gene is composed by 8 (9) exons
SMN1 and SMN2 share more than 99% nucleotide identity, and both are
capable of encoding SMN
Burges, A, McGovern, V. Genetics of Spinal Muscular Atrophy. Molecular and Cellular Therapies for Motor Neuron Diseases.2019
SMN Gene
Disruption of a
splice modulator
Transcription
Translation
100% Full length SMN 10% Full length SMN 90% Truncated SMNΔ7
Modified from Neuromuscular.wustl..edu2019
SMN Protein
Has a multidomain structure that provides a platform to recruit Gemins and small nuclear (sn)RNAs
Gemin2-binding domain (aa 19–44)
Tudor domain (aa 91–142)
Proline-rich domain (aa 195–248)
Tyrosine- and glycine-rich region (YG box; aa 268–279)
Burges, A, McGovern, V. Genetics of Spinal Muscular Atrophy. Molecular and Cellular Therapies for Motor Neuron Diseases.2019
Biochemical
Function of
SMN Complex
SMN complex consist of
o SMN
o Gemins2–8
o Unrip (unr-interacting protein)
o Sm proteins
SMN localizes to both nuclear and
cytosolic compartments
Functions:
Formation of small nuclear
ribonucleic proteins(snRNP) critical
for the correct splicing of all genes
Assembly of other RNP complexes
www.med.upenn.edu2019
Types of Defects
Loss of Phenotypic Severity
SMN1
Molecular Testing2019
Types of 95% Homozygous deletion of exon 7 and/or 8 or
gene conversion from SMN1 to SMN2**
Defects
5% compound heterozygosity for a point mutation
within the SMN1gene on one chromosome and a
deletion/gene conversion of SMN12019
Gene
Conversion
from SMN1
to SMN2
• **Severe missense mutations disrupt the ability of SMN to efficiently
oligomerize and therefore act much like SMN lacking the sequence
encoded by exon 7 (SMN1 converting to SMN2)
• This form of SMN is rapidly degraded and results in minimal amounts of
SMN protein2019
Phenotypic SMN2 copy
number
Type of SMN2
Severity
Determinant Other
s Trans-Acting
Phenotypic
Modifiers
Modifiers: PLS3 • Neuronal apoptosis
inhibitory protein
(NAIP) gene2019
SMN2 Copy Number
Type Highest Motor Function SMN 2 copy number
Type 0 Never sits or walks 1 copy
1a
Type 1 No independent sitting 1 or 2 copies (85%)
1b 3 copies (15%)
1c
Type 2 Independent sitting, some stand but never walk 3 copies ( 82%)
2 copies ( 11%)
4 copies( 7%)
Type 3 Independent walking but may lose ambulation 3 or 4 copies (96%) 2 copies (4%)
Type 4 Walks during adult years but may lose ambulation ≥4 copies
Wang CH, et al. J Child Neurol. 2007;22:1027-10492019
The output of SMN2 is critical to determinate the
phenotype
The ability to identify an intact SMN2 gene is not possible
with the current diagnostic testing
Type of
The variant c.859G>C in exon 7 of SMN2 results in
SMN2 Gene approx. 20% increase in full-length SMN protein and a
mild SMA phenotype (Type 2 or 3)
With current screening procedures we cannot obtain
precise information on whether these SMN2 genes are
fully intact and functional2019
SMN1 deletion/ copy number
SMN1 sequencing
Molecular
SMN2 copy number :
Testing
• Now routinely performed within the setting of
diagnostic or carrier testing for SMA
• SMN2 copy number analysis is important
stratifying patients who are more likely to
respond to therapeutic strategies
• Value within the setting of clinical trials2019
• Category 1: SMN1 exon 7 copy number of 1 and
presumes the presence of a SMN1 deletion/gene
Carrier conversion on the other chromosome (heterozygous)
Status • Category 2 : two SMN1 genes in cis on a single
chromosome along with a deletion/gene conversion
(1/40 to1/60) of SMN1 exon 7 on the opposite chromosome
resulting in a SMN1 exon 7 copy number of 2
• Category 3: subtle intragenic point mutation on one
chromosome resulting in an SMN1 exon 7 copy
number of ≥22019
• 25% risk for the fetus to be affected
• Amniocentesis can be performed after the
Prenatal 14th week of pregnancy, and is associated
with a risk of miscarriage 1 in 200
Testing • Chorionic Villus Sampling can be
performed as early as the 10th week of
pregnancy2019
Newborn
Screening
• Approved in the US at national
level in 2018
• Implementation is at discretion
of each state
CureSMA2019
Current Therapies and Research
on SMA
Diana Castro, MD
Assistant Professor of Pediatrics, Neurology and Neurotherapeutics
University of Texas Southwestern Dallas2019
Therapeutic Approaches
Motor Neuron
Modulation of the low functioning
SMN2 ”back up copy”
Replacement of SMN1
(gene transfer)
Neuroprotective Agents
**Myostatin Inhibitor
Copyright © motifolio.com2019
ORAL
Modulatio • Branaplan(LMI070 )
n of the • Risdiplam (RO7034067)
• FIREFISH
low • SUNFISH
• JEWELFISH
functionin
g SMN2 INTRATHECAL
• Nusinersen2019
Risdiplam
• Recruiting
• Oral medication- small molecule
• Selective SMN2 splicing modifier designed to bind with specificity to SMN2 pre-mRNA
• Promote inclusion of exon 7 and increase the production of functional SMN protein
FIREFISH SUNFISH JEWELFISH RAINBOWFISH2019
FIREFISH
• SMA Type 1 with 2 SMN2 copies
• 1-7 months
• Open label
• Part 1: safety, tolerability, dose selection -
completed
• Part 2: safety and efficacy in 40 participants
• Estimated study completion September 2020
ClinicalTrials.gov. CureSMA Annual Meeting 20192019
6.5-fold increase increase in SMN protein levels in blood after
4 wks.
19/21 infants (90%) remain alive with 2 having discontinued
due to the fatal progression of their disease
FIREFISH 3 patients are now over 24 m/old
RESULTS
None of the participants loss of ability to swallow, got
tracheostomy or permanent ventilation
Most common AEs were fever, diarrhea, URI, ear infections,
pneumonia, constipation, vomiting and cough2019
CHOP Spontaneous movement (upper
1 extremity)
2
Spontaneous movement (lower Type of CHOP Age at the Age at the
3
extremity)
Hand grip
Patient INTEND beginning of beginning of
Head in midline with visual Score the study SMA Sx
4 stimulation
5 Hip adductors Healthy Infants 50.1 points 3.3 months
6 Rolling: elicited from legs (n=14) (range: 32-62)
7 Rolling: elicited from arms
Shoulder and elbow flexion and
8 horizontal abduction Infants with 20.2 Points 3.7 months2019
Natural Hx. HINE SMA Type 1
Score = 0 Score = 1
Uses whole 33 patients:
Voluntary Grasp No grasp
hand
• 2 stronger infants received a score of
14/33(42%) 19/33(58%) 1, which persisted >2 years
Kick
Ability to kick No kicking horizontal, legs • 7 weaker infants received a score of
do not lift 0 in all the developmental
18/33(55%) 15/33(45%)
milestones
Unable to
Head control Wobbles
maintain upright
20/33(61%) 13/33(39%) Risdiplam:
Rolling No rolling • 7/17 can sit without support for ≧ 5 sec
Sitting Cannot sit • 1/17 stand up with support
Crawling Does not lift head
All patients scored 0
Does not support
Standing
weight
Walking No walking
Sanctis, RD et al. Neuromuscul Disord. 2015;26(11):754-759.2019
SUNFISH
• SMA type 2 or 3 ambulant or not
• Randomization: placebo or drug
• 2- 25 years
• Part 1: ideal dose (n=51)
• Part 2: safety and efficiency (n=158)
• Estimated completion: July 2020
ClinicalTrials.gov. CureSMA Annual Meeting 20192019
2-fold increase in SMN protein levels in blood
AE have been mostly mild and resolved despite ongoing treatment
58% had an improvement in Motor Function Measure (MFM32) over
SUNFISH baseline of 3 points or more after 1 year
Improvements were seen both in patients
RESULTS 12 years old (42%; n=19)
ClinicalTrials.gov. CureSMA Annual Meeting 20192019
JEWELFISH
• All types of SMA
• Open label
• 6 months to 60 years
• 125 participants
• Previously treated with an splicing modifier
(Nusinersen) or Olesoxime
• Estimated study completion December 2020
ClinicalTrials.gov. CureSMA Annual Meeting 20192019
>2- fold increase of SMN protein levels in blood
JEWELFISH 12 patients with type 2 or 3 SMA have been treated
RESULTS
To date, no drug-related AE’s leading to withdrawal have
been reported
•Ophthalmology monitoring did not show any evidence of the
retinal findings seen in preclinical monkey studies2019
RAINBOWFISH
• 2019
• Open label
• Asymptomatic infants
• Birth to 6 weeks of age (at first dose)
• 2 to 4 SMN2 copies
• All infants will receive Risdiplam for 24 months, followed by a 3-
year extension phase
• Primary endpoint: proportion of infants sitting without support x
5 sec. after 12 months of treatment (BSID-III)
• Secondary endpoints: long-term evaluation (2-5 years) of motor
milestone achievements and other developmental milestones
(CHOP, HINE)
ClinicalTrials.gov. CureSMA Annual Meeting 20192019
ORAL
•Branaplan(LMI070 )
Modulation •Risdiplam (RO7034067)
•FIREFISH
of the low •SUNFISH
•JEWELFISH
functionin
g SMN2 INTRATHECAL
•Nusinersen2019
AON Exon Inclusion
Transcription
Facilitating accurate splicing
of SMN2 transcripts:
Exon 7 increasing transcripts
Translation containing exon 7
SMN1 100% full ASO- binds to ISS-N1
length SMN protein (splice silencer dependent
on hnRNP protein) located
in intron 7.
ASO displaces hnRNP 90% Full length SMN protein
Modified from Neuromuscular.wustl..edu2019
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
CS1: SAD
CS2: MAD
Later CS12: CS10 & CS2 Re-dosing
Onset
CS10: CS1 Re-dosing
CS4 CHERISH: P3 Later-Onset
CS11 SHINE: OLE
CS3A: P2 open label
Infantile
Onset FDA approval
23Dec16
CS3B ENDEAR: P3 Infantile-
Onset
EMBRACE: P1
Other SMA CS7 EMBRACE: OLE:
Infants/Children
populations
NURTURE: P2 open label pre-symptomatic newborns
Phase 1 or 2 Phase 2 Phase 3 IONIS
Arrows do not accurately reflect timing IONIS Biogen
Biogen Clinical Program2019
Phase 2 open label
25 infants aged ≤ 6 weeks with pre-symptomatic, genetically
confirmed SMA
15 with 2 copies of SMN2 and 10 with 3 copies of SMN2
NURTURE
Primary endpoint
• All 25 patients are alive
• No participants required permanent ventilation, including
tracheostomy
• 4/25 (16%) participants required respiratory intervention
(>6 hrs./day continuously for >7days)2019
Pre-Symptomatic (NURTURE)
HINE Motor Milestones
30
25
20
15
10
5
0
Head control Sitting without Walking with Walking alone
support assistance
2 SMN2 Copies (n=15) 3 SMN2 Copies(n=10) Total (n=25)2019
NURTURE CHOP INTEND
70
NURTURE infants
Max CHOP INTEND score = 64a
60
In healthy infants, mean (SD) total
Mean (SE) CHOP INTEND
score was 47.2 (10.0) at Month 0
50 and 56.7 (5.8) at the 3-month
total score
40
Highest individual observed score over
the 2-year period was 33 in a natural
30 history cohort with 2 SMN2 copies
Highest mean (SE) score over
20 the 2-year period was 19.9 (1.7)
in a natural history cohort with
2 SMN2 copies
10
2 SMN2 copies
2 SMN2 copies SMN2
33SMN2 copies
copies
0
1 64 183 302 365 421 540 659 700 778
Mean (min, max) CHOP
Study visit day
INTEND
3 SMN2 copies, n 10 10 10 10 10 9 7
3 SMN2 copies = 62.6 (58, 64)
2 SMN2 copies = 61.0 (46, 64)
2 SMN2 copies, n 15 15 15 15 15 15 13 10 9 7
Kolb SJ, et al; NeuroNEXT Clinical Trial Network on behalf of the NN101 SMA
Biomarker Investigators. Ann Neurol. 2017;82(6):883-891.2019
At the time of the interim analysis (May 2018), patients were 14 to 34
mo.
All participants were alive and none required permanent ventilation,
including tracheostomy
NURTURE All (100%) participants have achieved sitting without support and
most (88%) have achieved walking with assistance and 77% are
walking alone
Summary
Early treatment of the pre-symptomatic infant allows for progressive
gains in motor function
Nusinersen was well tolerated and no specific drug-related safety
concerns were identified2019
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
CS1: SAD
CS2: MAD
Later CS12: CS10 & CS2 Re-dosing
Onset
CS10: CS1 Re-dosing
CS4 CHERISH: P3 Later-Onset
CS11 SHINE: OLE
CS3A: P2 open label
Infantile
Onset FDA approval
23Dec16
CS3B ENDEAR: P3 Infantile-
Onset
EMBRACE: P1
Other SMA CS7 EMBRACE: OLE:
Infants/Children
populations
NURTURE: P2 open label pre-symptomatic newborns
Phase 1 or 2 Phase 2 Phase 3 IONIS
Arrows do not accurately reflect timing IONIS Biogen
Biogen Clinical Program2019
SHINE
Sham in ENDEAR
Sham n=41
ENDEAR Sham in ENDEAR
Symptomatic Nusinersen in
SHINE2019
CHOP
CSMA (2019) Cure SMA - 2019 Annual Conference I Jun 28-Jul 1, 2019 I Anaheim, CA. Poster 62019
Nusinersen: Long-term Results
Mean change from baseline over ~3 Mean change from baseline in HFMSE
years of treatment score
Motor
assessment SMA Type II SMA Type III
HFMSE Score +10.8 points +1.8 points
Upper Limb Module
+4 points Not reported
Score
Six-minute Walk
Not reported +92 meters
Test Distance
• CMAP values remained relatively stable
• No children discontinued treatment due
to AEs
Darras BT, et al. Neurology. 2019;92:e2492–e25062019
Nusinersen
o FDA approved in 2016 for pediatrics and adults
o Baseline labs and prior to each dose: PLT count, PT, and U/A
o Administered intrathecally
• Recommended dosage is 12 mg/5 mL per administration
o First 3 loading doses should be administered at 14-day intervals
o Fourth loading dose should be administered 30 days after the 3rd dose
o Maintenance dose should be administered once every 4 months thereafter
• SPINRAZA® PI 2016. 49
These materials are provided to you solely as an educational resource for your personal use. Any commercial use or distribution of these materials or any portion thereof is strictly prohibited.2019
Dosing Information
2 weeks 2 weeks 30 days 4 months
Inj. Inj. Inj. Inj. Inj. Every
1 2 3 4 4 months
{Loading doses} {Maintenance}
• Lumbar puncture
• Nusinersen is administered over 1-3 minutes
• Dose 12 mg (5 ml)
• Labs: CBC, PT, PTT, urine protein2019 Videos
2019
Therapeutic Approaches
Motor Neuron
Modulation of the low functioning
SMN2 ”back up copy”
Replacement of SMN1
(gene transfer)
Neuroprotective Agents
**Myostatin Inhibitor
Copyright © motifolio.com2019
AVXS- 101 Gen Transfer
AAV9
SMN1
Vector
• Self-complementary AAV9 (A non-
replicating adeno-associated virus)
• Delivery functional human SMN gene
Completed Phase 1 (2017)
15 patients SMA type 1 Cohort-1 (6.3 m) n =3 small • Safety, tolerability
dose • Time to death
2 copies of SMN2
and permanent
6 male, 9 female Cohort-2 (3.4 m) n =12 large ventilation
IV 1 hr. infusion dose2019
• Safe (4.6 years)
• Improves survival
• All patients are alive and only 1 patient (Cohort 1)
reached the pulmonary endpoint at 28 months
AVXS- • None of the patients in Cohort 1 were able to sit
without support, or to stand or walk
101 • Patients in Cohort 2 demonstrated improvements in
motor function:
Results o 11/12 have head control
o 11/12 sit unassisted > 30 sec
o 2 patient stand with assistance
o 2 patients can crawl, stand and walk
independently
24th International Annual Congress of the World Muscle Society, Copenhagen, Denmark, 1–5 October 20192019 STR1VE • Phase 3 • SMA type 1 with 2 SMN2 •
2019
SPR1NT
• Phase 3
• Pre-symptomatic SMA < 6wks
• 2 copies of SMN2: 15
• 3 copies of SMN2: 12
24th International Annual Congress of the World Muscle Society, Copenhagen, Denmark, 1-5 October 20192019
STRONG
EPNS Congress, Athens, Greece, September 17-21 20192019
STRONG
• 30 Patients enrolled
• Dose A: 3
• Dose B:
o 6-24 m: 13
o 24-60 m: 12
• Dose C: 2
EPNS Congress, Athens, Greece, September 17-21 20192019 FDA Onasemnogene Abeparvovec-xioi • Approved May 31st for patients < 2years of age • No weight limit • AAV9 < 1:50 • Baseline Labs: LFTs , Troponin, CBC, PT, PTT and Q1 wks. x 4, Q2 wks. x 2months • Dose: 1.1x 10¹⁴ vector genomes (vg) per Kg of body weight • IV infusion over 60 min • Prednisone 1mg/kg/day pre and post treatment for 1 month then taper over 2 months
2019 Videos
2019
Phase 2 active treatment study to evaluate the efficacy and
safety of SRK-015 in patients with later-onset SMA
Enrolling
SRK - 015 Estimated completion April 2021
SRK-015 is a fully human anti-pro Myostatin monoclonal
antibody (mAb) of the immunoglobulin G4 (IgG4)/lambda
isotype that binds to human pro/latent myostatin
IV infusion every 4 weeks
ClinicalTrials.gov NCT039215282019
Cohort 1: SMA Type 3 ambulatory (n:20) on or off another SMA
therapy. Open-label, 20 mg/kg SRK-015
Cohort 2: SMA Type 2 and non-ambulatory Type 3 (n:15). Patients
SRK-015 already receiving an approved SMN up regulator therapy initiated at
age 5 or older. Open-label, 20 mg/kg SRK-015
Cohort 3: SMA Type 2 < 5 years (n:20). Patients receiving an
approved SMN up regulator therapy initiated before the age of 5
years old. Double-blind, randomized 1:1 to: 20 mg/kg or 2 mg/kg
SRK-015
ClinicalTrials.gov NCT039215282019 Are You Ready? Julie A. Parsons, MD Haberfeld Endowed Chair in Pediatric Neuromuscular Disorders Professor of Clinical Pediatrics and Neurology University of Colorado School of Medicine
2019 Warning Videotaping or taking pictures of the slides associated with this presentation is prohibited. The information on the slides is copyrighted and cannot be used without permission and author attribution.
2019
Financial Disclosures
I have participated in clinical trials for:
• Biogen
• Isis/Ionis
• Cytokinetics
• AveXis
• Genentech/Roche
• Sarepta
• PTC Therapeutics
• Scholar Rock2019 System Challenges with the Introduction of New Therapies
2019 Objectives • Understand some of the challenges of start up when a trial drug is approved for a rare disease • Understand some of the key aspects of system development to support a treatment plan • Identify barriers to clinical treatment
2019 Introduction • Basic science allows development of specialized drugs for rare disorders • These drugs or products are carefully tested for safety and efficacy in clinical trials • Some of these drugs are then approved and brought into the commercial market to be used for treatment
Challenges in Trials to
2019
Treatment
• Providing prompt and effective education about the disease,
treatment, delivery system, and possible medical issues
• Establishing a protocol for treatment
• Establishing an Administrative infrastructure
o Scheduling
o Preauthorization
o Insurance
o PaymentChallenges in Trials to
2019
Treatment
• Clinical trials are run in a very rigidly controlled
environment which is monitored and regulated closely
• Adequate staffing and oversight is guaranteed both by
internal and by external oversight
• Patient safety and outcomes are closely watched and
documented
• Ideally all costs are budgeted for and compensated2019 Differences between Trials and Treatment • Finances and Controlled Environment
2019 Control • Clinical trial process and regulation guarantees that there is a standardized, controlled environment for drug delivery and outcome evaluation. • Then the schema changes to free market with commercial and financial interests at play.
2019 Finances • Clinical trials are fully funded • Research and medical team are compensated • Institutional and administrative costs are paid • Pharmacy procurement and processing is specified • Patient travel and expenses are reimbursed
2019
The Players Medical
Third Party Team
Payers
Patients
Pharma Hospital
Company Administrati
on2019 Reminder • These are rare diseases!!
2019 Patients • Want treatment immediately as soon as it is available • Not always fully informed as to risks and benefits • Many times do not fully understand the medical or financial implications of treatment • Social media plays a prominent role
2019 Medical Team Providers • Change from research team to clinical medicine team • Want to safely provide the approved novel therapy • Not always familiar with the drug, delivery system, risks and benefits • No organized safety reporting or sharing experience and standardized outcomes
2019 Hospital Administration • Cost of novel medication requires upper level management be involved early in discussions about treatment • Look to limit financial risk and liability o Chief Financial Officer o Chief Medical Officer o Pharmacy Manager o Finance and revenue recovery specialists o Business Manager/Operations coordinator o Government advocate
2019 Pharmacy • Pharmacy and Therapeutics committee must approve addition of the drug to formulary • Process of “white bagging”, “buy and bill”, specialty pharmacy • Special preparation, processing and handling of drug when it is dispensed or administered.
2019 Pharma Company • Offer support systems to patients • Offer support systems to providers • Believe all patients should be treated with their product • Change from research medical team to commercial team • Internal communication not always consistent
2019 Colorado Experience • Participated in clinical trials for nusinersen and onasemnogene abeparvovec for spinal muscular atrophy patients • Medical research team Medical care team
2019 Rocky Mountain Region
2019 Complex Drug Program • Medical Director • Operations Coordinator • Nurse Manager
2019 Neurology Complex Drugs Program • Operations Coordinator o Central point of contact o Manages all of the complex scheduling o Interfaces with the hospital preauthorization and finance team. o Manages the status of insurance referrals, denials, appeals, etc o Partners with Nurse Coordinator
2019
Neurology Complex Drugs
Program
• Clinical Nurse Coordinator
o Medical point of contact for patients
o Provides education to nursing personnel
o Meets with patient and family to review the Memo of Understanding
and answer questions prior to initiation of therapy
o Pends laboratory and medication orders to be reviewed and signed
o Often sees patient on the procedure day
o Post procedure follow up phone calls2019 Neurology Complex Drugs Program • High Risk Medical Team o Neurologist o Anesthesiologist o Gastroenterologist/Nutrition o Pulmonologist/RT o Interventional Radiologist o Neurosurgeon o Orthopedic Surgeon o Social Work o Complex Drug Program Team
2019 Memo of Understanding • States our team’s responsibilities • States the patient and family responsibilities o Following consensus guidelines o Immunizations o Nutrition o Routine follow up appointments
2019 SMA Consensus Care Guidelines
2019 Consensus of Care Guidelines for SMA • Important that in light of new therapies, care guidelines continue to be followed. • New therapies are not a replacement for good general health care. • Reminder: There is no cure for SMA
2019 Third Party Payers • Often have little knowledge about the rare disorder or the treatment • Might not have a code or policy in place to approve the drug or delivery system for that drug • Includes Medicaid for many patients • May require journal articles and published results for evidence based medicine requirements • Dictate strict outcome measurement monitoring that might not be needed • May be slow in developing a policy regarding treatments
2019
Spinraza Process
•Patient is evaluated in the Neuromuscular Clinic to determine interest in treatment
Neurology
•Letter of Medical Necessity is developed
•Prior Authorization or Pre-determination Request is submitted to insurance
Insurance •Authorization must be received prior to scheduling
Verification
•Verify payer is contracted with hospital
•Verify payer reimbursement is sufficient for both procedure and medication
Managed
Care •Negotiate Single Case Agreement if needed
•Patient is evaluated by High Risk team to determine the best procedure treatment plan
•Pertinent information related to treatment (anesthesia plan, pulmonary concerns, recovery plan) documented in chart (EMR)
High Risk
Eval
•Scheduling orders are placed
Scheduling
•Medication and safety lab orders are placed in chart
•Pharmacy buyers order medication for each scheduled appointment
Pharmacy
•Our institution is a “buy-and-bill” institution
•Safety labs are obtained before the procedure
•Medication is administered
IR or PC
•Submit claim to payer
Patient
Financial
•Confirm correct payment is made to hospital
Services2019 Lessons Learned • Engage hospital administration early • Patients want treatment now. Keep them informed and up to date • P and T committees take time for investigation and approval • Pharma access to care programs have benefits and challenges • White bagging vs buy and bill, specialty pharmacies • Insurance is a complex field to navigate • Peer to peer calls are time consuming
2019
Conclusions
• Clinical treatment is a complex process
• Advanced planning is necessary
• Teamwork is a requirement
This Photo by Unknown Author is licensed under CC BY
• Good communication and education of all parties involved is key2019 Share Your Feedback • Please use the 2019 AANEM Annual Meeting app to rate this presentation and the speaker(s). • Your feedback helps us enhance our annual meeting to ensure we are continuing to meet your needs.
2019 • Claiming CME • Course and Plenary Presentations Visit: www.aanem.org/resources Record your attendance hours after each session or do it all at once after the meeting is complete! Credit not recorded by December 15, 2019 will not be reported to ABPN and ABPMR. The AANEM will report ALL Annual Meeting attendees’ credit to ABPN and ABPMR by December, 31, 2019.
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