Clinical Development
`Success Rates
`2006-2015
`
`Biomedtracker
`
`Pharma intelligence |
`
`June 2016
`
`Abraxis EX2016
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`IPR2018-00151; IPR2018-00152; IPR2018-00153
`
`

`

`About BIO
`
`BIO is the world’s largest trade association representing biotechnology companies, academic institutions, state biotechnology
`centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in
`the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products. BIO
`also produces the BIO International Convention, the world’s largest gathering of the biotechnology industry, along with industry-
`leading investor and partnering meetings held around the world.
`
`About Biomedtracker
`
`BioMedTracker, a subscription-based product of Informa, tracks the clinical development and regulatory history of investigational
`drugs to assess its Likelihood of Approval (LOA) by the FDA. BioMedTracker is populated in near real-time with updated
`information from press releases, corporate earnings calls, investor and medical meetings and numerous other sources.
`
`About Amplion
`
`Amplion is the leading biomarker business intelligence company, and its flagship product BiomarkerBase™, along
`with consulting services and free reports, deliver insights that inform key strategic decisions for drug and diagnostic
`test developers. Since 2012 Amplion has helped large and small companies alike make the best use of biomarkers in
`advancing precision therapeutics and next generation diagnostics. BiomarkerBase is a subscription-based service that
`tracks biomarker usage in clinical trials, drug labels, and tests (including laboratory-developed, FDA-cleared, and FDA-
`approved tests). BiomarkerBase is updated weekly with information from these sources and publications, using supervised
`machine learning algorithms for natural language processing (Amplion BiomarkerEngine) to identify biomarkers.
`
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`

`Executive Summary
`
`This is the largest study of clinical drug development success rates to date. Over the last decade, 2006-2015, a total of 9,985
`clinical and regulatory phase transitions were recorded and analyzed from 7,455 development programs, across 1,103 companies
`in the Biomedtracker database. Phase transitions occur when a drug candidate advances into the next phase of development or is
`suspended by the sponsor. By calculating the number of programs progressing to the next phase vs. the total number progressing
`and suspended, we assessed the success rate at each of the four phases of development: Phase I, II, III, and regulatory filing.
`Having phase-by-phase data in hand, we then compared groups of diseases, drug modalities and other attributes to generate
`the most comprehensive analysis yet of biopharmaceutical R&D success.
`
`This work was made possible due to the years of clinical program monitoring and data entry by Informa’s Biomedtracker service.
`BIO has long partnered with Biomedtracker to calculate success rates based on this data. More recently, BIO and Biomedtracker
`partnered with Amplion, the inventors of BiomarkerBase, to analyze the effects of biomarkers in clinical trial success.
`
`Key takeaways:
`
`• The overall likelihood of approval (LOA) from Phase I for all developmental candidates was 9.6%, and 11.9% for
`all indications outside of Oncology.
`
`• Rare disease programs and programs that utilized selection biomarkers had higher success rates at each
`phase of development vs. the overall dataset.
`
`• Chronic diseases with high populations had lower LOA from Phase I vs. the overall dataset.
`
`• Of the 14 major disease areas, Hematology had the highest LOA from Phase I (26.1%) and Oncology had the
`lowest (5.1%).
`
`• Sub-indication analysis within Oncology revealed hematological cancers had 2x higher LOA from Phase I
`than solid tumors.
`
`• Oncology drugs had a 2x higher rate of first cycle approval than Psychiatric drugs, which had the lowest percent
`of first-cycle review approvals. Oncology drugs were also approved the fastest of all 14 disease areas.
`
`• Phase II clinical programs continue to experience the lowest success rate of the four development phases, with
`only 30.7% of developmental candidates advancing to Phase III.
`
`Biomedtracker
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`

`Disease areas covered in this report:
`
`• Allergy
`
`• Autoimmune
`
`• Cardiovascular
`
`• Chronic High Prevalence Diseases
`
`• Endocrine
`
`• Gastroenterology
`
`• Hematology
`
`•
`
`Infectious Disease
`
`• Metabolic
`
`• Neurology
`
`• Oncology
`
`• Ophthalmology
`
`• Psychiatry
`
`• Rare Diseases
`
`• Respiratory
`
`• Urology
`
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`

`Table of Contents
`
`Introduction ................................................................................................................................................................... 6
`
`Phase Success and Likelihood of Approval (LOA) – Overall .............................................................7
`
`Phase Success and Likelihood of Approval (LOA) – by Disease ................................................... 8
`
`Oncology and Non-Oncology Diseases ........................................................................................13
`
`Rare and Chronic High Prevalence Disease ...............................................................................16
`
`Patient Selection Biomarkers ..............................................................................................................18
`
`Phase Success and Likelihood of Approval (LOA) – by Drug Classification .......................20
`
`Discussion ....................................................................................................................................................................22
`
`Methods ........................................................................................................................................................................ 24
`
`References .................................................................................................................................................................. 26
`
`
`
`
`
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`

`Introduction
`
`This study aimed to measure clinical development success rates to strengthen benchmarking metrics for drug development. To
`measure success rates for investigational drugs, we analyzed individual drug program phase transitions from January 1, 2006 to
`December 31, 2015. For the ten years studied, 9,985 transitions in the Biomedtracker database were analyzed. A phase transition
`is the movement out of a clinical phase – for example, advancing from Phase I to Phase II development, or being suspended
`after completion of Phase I development.
`
`These transitions occurred in 7,455 clinical drug development programs, across 1,103 companies (both large and small), making
`this the largest study of its kind. With this broad set of data, we aimed to capture the diversity in drug development across levels
`of novelty, molecular modalities, and disease indications.
`
`Only company-sponsored, FDA registration-enabling development programs were considered; investigator-sponsored studies
`were excluded from this analysis. A more detailed description of the data collection, composition, and analysis methodology
`are described at the end of this report under “Methods.”
`
`Individual Phase transition success rates were determined by dividing the number that advanced to the next phase by the total
`number advanced and suspended. This “advanced and suspended” number is often referred to as “n” in this report, and should
`be taken into account when drawing conclusions from the success rate results.
`
`One of the key measures of success used in this report is the Likelihood of Approval (LOA) from Phase I. This LOA success rate
`is simply a multiplication of all four Phases success rates, a compounded probability calculation. For example, if each phase had
`a 50% chance of success, then the LOA from Phase I would be 0.5 x 0.5 x 0.5 x 0.5 = 6.25%.
`
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`

`Phase Transition Success and Likelihood
`of Approval (LOA) - Overall
`
`Consistent with previous studies of drug development phase transition success rates, we found Phase II success rates to be far
`lower than any other phase.1 Phase I and III rates were substantially higher than Phase II, with Phase I slightly higher than Phase
`III. The highest success rate of the four development phases was the NDA/BLA filing phase.
`
`The Phase I transition success rate was 63.2% (n=3,582). As this Phase is typically conducted for safety testing and is not
`dependent on efficacy results for candidates to advance, it is common for this phase to have the highest success rate among the
`clinical phases across most categories analyzed in this report. Phase I success rates may also benefit from delayed reporting bias,
`as some larger companies may not deem failed Phase I programs as material and thereby not report them in the public domain.
`The Phase II transition success rate (30.7%, n=3,862) was substantially lower than Phase I, and the lowest of the four phases
`studied. As this is generally the first stage where proof-of-concept is deliberately tested in human subjects, Phase II consistently
`had the lowest success rate of all phases. This is also the point in development where industry must decide whether to pursue
`the large, expensive Phase III studies and may decide to terminate development for multiple reasons including commercial
`viability. The second-lowest phase transition success rate was found in Phase III (58.1%, n=1,491). This is significant as most
`company-sponsored Phase III trials are the longest and most expensive trials to conduct.
`
`The probability of FDA approval after submitting a New Drug Application (NDA) or Biologic License Application (BLA), taking
`into account re-submissions, was 85.3% (n=1,050). Multiplying these individual phase components to obtain the compound
`probability of progressing from Phase I to U.S. FDA approval (LOA) reveals that only 9.6% (n=9,985) of drug development
`programs successfully make it to market (Figure 1).
`
`Probablity of Success
`
`85.3%
`
`63.2%
`
`58.1%
`
`30.7%
`
`9.6%
`
`Phase I to
`Phase II
`
`NDA/BLA to
`Phase III to
`Phase II to
`Approval
`NDA/BLA
`Phase III
`All Diseases, All Modalities
`
`Phase I to
`Approval
`
`90%
`
`80%
`
`70%
`
`60%
`
`50%
`
`40%
`
`30%
`
`20%
`
`10%
`
`0%
`
`Probability of Success
`
`Figure 1. Phase transition success rates and LOA from Phase I for all diseases, all modalities.
`
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`Phase Transition Success and Likelihood
`of Approval (LOA) - by Disease
`
`We segmented major disease areas according to the convention used by Biomedtracker, and categorized 21 major diseases
`and 558 indications for the 2006-2015 timeframe. For reporting at the disease area level, we analyzed only major diseases
`with more than 100 total transitions from Phase I to NDA/BLA approval. This resulted in 14 categorized disease areas: Allergy,
`Autoimmune, Cardiovascular, Endocrine, Hematology, Infectious disease, Gastroenterology (non-IBD), Metabolic, Neurology,
`Oncology, Ophthalmology, Psychiatry, Respiratory, and Urology. Disease areas with n <100 were placed into the “Other” category.
`This includes Dermatology, Renal, Obstetrics, Rheumatology (for non-autoimmune indications), Dental, and Orthopedics.
`
`As can be seen in Figures 2a, there is a wide range of Likelihood of Approval (LOA) from Phase I. At the high end, Hematology
`towers over the other groups at 26.1% (n=283). A large portion of Hematology transitions came from Hemophilia, Anemia,
`and Blood Protein Deficiencies, Thrombocytopenia, and Hemostasis. Some of these Hemophilia indications had overall LOA
`that reached above 50%. This more than offset some of the weaker Hematology success rates that were observed in Venous
`Thromboembolism and Neutropenia. Hematology’s LOA from Phase I was 5x the success rate for Oncology, which at 5.1%
`(n=3,163) had the lowest of all the major disease areas.
`
`The next-highest LOA from Phase I under Hematology’s 26.1% was Infectious Disease with an impressive 19.1% (n=916).
`Five disease areas follow closely in the 14-17% range: Ophthalmology > Other > Metabolic > Gastroenterology > Allergy.
`Below 14% there is a third group of diseases that was slightly above the overall average of 9.6%: Endocrine > Respiratory >
`Urology > Autoimmune. Falling under the overall LOA of 9.6% was a fourth group made up of four disease areas: Neurology >
`Cardiovascular > Psychiatry > Oncology. The fact that Oncology and Neurology had the two highest n values while also having
`low LOA values suggests that these two disease categories are a significant factor in bringing down the overall industry LOA.
`
`Likelihood of Approval from Phase I
`
`19.1%
`
`17.1% 16.3%
`
`15.3% 15.1% 14.7%
`
`13.2% 12.8%
`
`11.4% 11.1%
`
`9.6%
`
`8.4%
`
`6.6% 6.2%
`
`5.1%
`
`26.1%
`
`30%
`
`25%
`
`20%
`
`15%
`
`10%
`
`5%
`
`0%
`
`LOA from Phase I
`
`Phase III to NDA/BLA
`Phase II to Phase III
`Phase I to Phase II
`Phase Success
`Figure 2a. Chart of LOA from Phase I, displayed highest to lowest by disease area.
`Advanced or
`Advanced or
`Advanced or
`Phase Success
`Phase Success
`Suspended
`Suspended
`Suspended
`86
`83
`64
`Hematology
`347
`286
`150
`Infectious disease
`66
`101
`60
`Ophthalmology
`96
`116
`46
`Other
`95
`84
`35
`Metabolic
`Gastroenterology*
`41
`56
`33
`37
`40
`14
`Allergy
`299
`242
`143
`Endocrine
`150
`196
`45
`Respiratory
`21
`52
`21
`Urology
`8 | BIO Industry Analysis
`297
`319
`135
`Autoimmune
`3582
`3862
`1491
`All Indications
`462
`465
`216
`Neurology
`209
`237
`110
`Cardiovascular
`154
`169
`70
`Psychiatry
`1222
`1416
`349
`Oncology
`
`73.3%
`69.5%
`84.8%
`66.7%
`61.1%
`75.6%
`67.6%
`58.9%
`65.3%
`57.1%
`65.7%
`63.2%
`59.1%
`58.9%
`53.9%
`62.8%
`
`56.6%
`42.7%
`44.6%
`39.7%
`45.2%
`35.7%
`32.5%
`40.1%
`29.1%
`32.7%
`31.7%
`30.7%
`29.7%
`24.1%
`23.7%
`24.6%
`
`Phase Success
`
`75.0%
`72.7%
`58.3%
`69.6%
`71.4%
`60.6%
`71.4%
`65.0%
`71.1%
`71.4%
`62.2%
`58.1%
`57.4%
`55.5%
`55.7%
`40.1%
`
`NDA/BLA to Approval
`
`Advanced or
`Suspended
`50
`133
`40
`43
`27
`26
`16
`107
`37
`14
`86
`1050
`161
`76
`58
`176
`
`Phase Success
`
`84.0%
`88.7%
`77.5%
`88.4%
`77.8%
`92.3%
`93.8%
`86.0%
`94.6%
`85.7%
`86.0%
`85.3%
`83.2%
`84.2%
`87.9%
`82.4%
`
`Likelihood of Approval
`
`Phase I to Approval
`
`Phase II to Approval
`
`Phase III to Approval
`
`NDA/BLA to Approval
`
`Hematology
`
`LOA n
`283
`
`Phase LOA
`26.1%
`
`LOA n
`197
`
`Phase LOA
`35.7%
`
`LOA n
`114
`
`Phase LOA
`63.0%
`
`LOA n
`50
`
`Phase LOA
`84.0%
`
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`

`19.1%
`
`17.1% 16.3%
`
`15.3% 15.1% 14.7%
`
`13.2% 12.8%
`
`11.4% 11.1%
`
`9.6%
`
`8.4%
`
`6.6% 6.2%
`
`5.1%
`
`20%
`
`15%
`
`10%
`
`5%
`
`0%
`
`LOA from Phase I
`
`Phase Success
`
`Phase I to Phase II
`
`Phase II to Phase III
`
`Phase III to NDA/BLA
`
`NDA/BLA to Approval
`
`Hematology
`Infectious disease
`Ophthalmology
`Other
`Metabolic
`Gastroenterology*
`Allergy
`Endocrine
`Respiratory
`Urology
`Autoimmune
`All Indications
`Neurology
`Cardiovascular
`Psychiatry
`Oncology
`
`Advanced or
`Suspended
`86
`347
`66
`96
`95
`41
`37
`299
`150
`21
`297
`3582
`462
`209
`154
`1222
`
`Phase Success
`
`73.3%
`69.5%
`84.8%
`66.7%
`61.1%
`75.6%
`67.6%
`58.9%
`65.3%
`57.1%
`65.7%
`63.2%
`59.1%
`58.9%
`53.9%
`62.8%
`
`Advanced or
`Suspended
`83
`286
`101
`116
`84
`56
`40
`242
`196
`52
`319
`3862
`465
`237
`169
`1416
`
`Phase Success
`
`56.6%
`42.7%
`44.6%
`39.7%
`45.2%
`35.7%
`32.5%
`40.1%
`29.1%
`32.7%
`31.7%
`30.7%
`29.7%
`24.1%
`23.7%
`24.6%
`
`Advanced or
`Suspended
`64
`150
`60
`46
`35
`33
`14
`143
`45
`21
`135
`1491
`216
`110
`70
`349
`
`Phase Success
`
`75.0%
`72.7%
`58.3%
`69.6%
`71.4%
`60.6%
`71.4%
`65.0%
`71.1%
`71.4%
`62.2%
`58.1%
`57.4%
`55.5%
`55.7%
`40.1%
`
`Advanced or
`Suspended
`50
`133
`40
`43
`27
`26
`16
`107
`37
`14
`86
`1050
`161
`76
`58
`176
`
`Phase Success
`
`84.0%
`88.7%
`77.5%
`88.4%
`77.8%
`92.3%
`93.8%
`86.0%
`94.6%
`85.7%
`86.0%
`85.3%
`83.2%
`84.2%
`87.9%
`82.4%
`
`Likelihood of Approval
`
`Phase I to Approval
`
`Phase II to Approval
`
`Phase III to Approval
`
`NDA/BLA to Approval
`
`Hematology
`Infectious disease
`Ophthalmology
`Other
`Metabolic
`Gastroenterology*
`Allergy
`Endocrine
`Respiratory
`Urology
`Autoimmune
`All Indications
`Neurology
`Cardiovascular
`Psychiatry
`Oncology
`
`LOA n
`283
`916
`267
`301
`241
`156
`107
`791
`428
`108
`837
`9985
`1304
`632
`451
`3163
`
`Phase LOA
`26.1%
`19.1%
`17.1%
`16.3%
`15.3%
`15.1%
`14.7%
`13.2%
`12.8%
`11.4%
`11.1%
`9.6%
`8.4%
`6.6%
`6.2%
`5.1%
`
`LOA n
`197
`569
`201
`205
`146
`115
`70
`492
`278
`87
`540
`6403
`842
`423
`297
`1941
`
`Phase LOA
`35.7%
`27.5%
`20.1%
`24.4%
`25.1%
`20.0%
`21.8%
`22.4%
`19.6%
`20.0%
`17.0%
`15.3%
`14.2%
`11.2%
`11.6%
`8.1%
`
`LOA n
`114
`283
`100
`89
`62
`59
`30
`250
`82
`35
`221
`2541
`377
`186
`128
`525
`
`Phase LOA
`63.0%
`64.5%
`45.2%
`61.5%
`55.6%
`55.9%
`67.0%
`55.9%
`67.3%
`61.2%
`53.5%
`49.6%
`47.8%
`46.7%
`49.0%
`33.0%
`
`LOA n
`50
`133
`40
`43
`27
`26
`16
`107
`37
`14
`86
`1050
`161
`76
`58
`176
`
`Phase LOA
`84.0%
`88.7%
`77.5%
`88.4%
`77.8%
`92.3%
`93.8%
`86.0%
`94.6%
`85.7%
`86.0%
`85.3%
`83.2%
`84.2%
`87.9%
`82.4%
`
`Figure 2b. Phase transition success and LOA by disease. Table of phase transition success and LOA by disease with corresponding n values.
`‘Advanced or Suspended’ refers to the total number of transitions used to calculate each success rate, with the n value noted in the text.
`The LOA n value is the total ‘Advanced or Suspended’ transitions of all phases used to calculate LOA. ‘Phase Success’ is the probability of
`successfully advancing to the next phase, whereas ‘Phase LOA’ is the probability of FDA approval for drugs from this phase of development.
`*Gastroenterology does not include IBD.
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`

`Phase I Transition Success Rates by Disease
`
`Success rates for Phase I ranged from 53.9% to 84.8%, with the average for all disease indications coming in at 63.2%. Looking
`at the distribution, we find that most disease area Phase I success rates cluster within +/-10% of the overall Phase I success
`rate. Two disease areas were outliers, and they are both to the upside. Ophthalmology registered an 84.8% (n=66) success rate,
`which was substantially higher (by >20%) than the overall Phase I success rate. Gastroenterology programs also exhibited an
`above average rate of successfully overcoming initial clinical safety hurdles with a 75.6% (n=41) Phase I success rate.
`
`Phase II Transition Success Rates by Disease
`In every disease area, Phase II had the lowest transition success rate of the four phases. As shown in Figure 3, Phase II success
`rates ranged from a high of 56.6% (Hematology, n=83) to a low of 23.7% (Psychiatry, n=169). Although it is widely known that
`drug program attrition is high in Phase II, it is interesting to find that the rate of success can vary by 33% among disease groups.
`The only Phase II success rate above 50% was seen in Hematology, which largely explains how that indication attained the
`highest LOA from Phase I.
`
`Excluding Hematology, we can group the Phase II success rates into three clusters: success rates below the 30% overall
`success rate, those 31-36%, and those in the 40-45% range. Unlike what is observed in the LOA from Phase I, Oncology does
`not have the lowest success rate for Phase II. Cardiovascular and Psychiatry both registered slightly below the 25% success
`rate seen for Oncology.
`
`Probability of Phase II Success
`
`45% 45% 43%
`
`40% 40%
`
`36%
`
`33% 33% 32% 31% 30% 29%
`
`25% 24% 24%
`
`60%
`
`57%
`
`50%
`
`40%
`
`30%
`
`20%
`
`10%
`
`0%
`
`Phase II Success Rate
`
`Figure 3. Phase II transition success rates by disease area. Categories are listed from highest to lowest based on the probability of
`transitioning from Phase II to Phase III. *Gastroenterology does not include IBD.
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`

`Phase III Transition Success Rates by Disease
`For Phase III transition success rates, Oncology was the outlier with the lowest transition success rate. As seen in Figure 4, the
`Phase III success rates for 14 specific disease areas clustered into two ranges: near 70% and 55-65%. This places Oncology
`into a group of its own at just 40.1% (n=349).
`
`In addition to Oncology, Neurology, Psychiatry and Cardiovascular were also below the overall Phase III success rate of 58.1%
`(n=1,491) at 57.4%, 55.7%, and 55.5%, respectively. Each of these areas included disease indications with large patient populations.
`Later in this report, we break down these high prevalence diseases and compare them with low prevalence disease areas.
`
`Probability of Phase III Success
`75% 73% 71% 71% 71% 71% 70%
`
`65%
`
`62% 61% 58% 58% 57% 56% 55%
`
`40%
`
`80%
`
`70%
`
`60%
`
`50%
`
`40%
`
`30%
`
`20%
`
`10%
`
`0%
`
`Phase III Success
`
`
`Figure 4. Phase III transition success rates by disease area. Categories are listed from highest to lowest based on the probability of transitioning
`from Phase II to NDA/BLA filing. *Gastroenterology does not include IBD.
`
`BIO Industry Analysis | 11
`
`Abraxis EX2016
`Apotex Inc. and Apotex Corp. v. Abraxis Bioscience, LLC
`IPR2018-00151; IPR2018-00152; IPR2018-00153
`
`

`

`NDA/BLA Submission Success Rates
`NDA/BLA transition success rates (approval rates) for the disease areas listed in Figure 2b ranged from the low end of 77.5%
`(Ophthalmology) to a high of 94.6% (Respiratory). The distribution of rates (17.1%) were within the tightest range among the
`four phases analyzed in this report. These rates are the result of eventual success, not success on first review, meaning some
`programs may have as many as four Complete Response Letters (CRLs) and attempts at approval. This unrestricted time-frame
`and number of re-submissions pushes the overall success above 85% across all diseases.
`
`When looking at how many original NDA/BLA filings were approved on the first review by FDA, the rates are far from concentrated
`(Figure 5). In fact, Psychiatry had only a 37% chance of first-cycle approval vs. Oncology at nearly 80%. Although this is an
`extreme range, upon subsequent submissions and reviews, both of these disease areas ended up with 91% of original drug
`indication applications being approved. There was a large increase in cumulative success rates after the second submission,
`but only marginal increases after the third review.
`
`Time from filing to approval also varied by disease area. Neurology drugs took the longest to approve on average, at 2 years,
`while Oncology drugs were approved almost twice as fast at 1.1 years. Many Oncology drugs for unmet medical need may have
`benefited from expedited approval pathways and associated increased interactions with FDA such as Breakthrough Therapy
`and Accelerated Approval, contributing to the faster overall time to approval. As might be expected, calculating time to approval
`for all disease areas put the time to approval in the middle of these extremes, at 1.6 years.
`
`Disease Area
`
`Oncology
`Allergy
`Respiratory
`Cardiovascular
`Infectious disease
`Urology
`Autoimmune
`Metabolic
`Ophthalmology
`All Diseases
`Hematology
`Gastroenterology
`Endocrine
`Neurology
`Psychiatry
`
`% Approved on
`1st Review
`
`% Approved by
`2nd Review
`
`% Ultimately
`Approved
`
`79%
`71%
`71%
`69%
`69%
`64%
`63%
`63%
`62%
`61%
`60%
`56%
`56%
`45%
`37%
`
`89%
`93%
`94%
`83%
`86%
`73%
`82%
`83%
`69%
`80%
`76%
`84%
`77%
`70%
`70%
`
`89%
`93%
`94%
`85%
`92%
`82%
`86%
`83%
`73%
`86%
`90%
`92%
`83%
`81%
`91%
`
`Filing to
`Approval Time
`(Years)
`1.1
`1.3
`1.6
`1.4
`1.4
`1.7
`1.6
`1.5
`1.3
`1.6
`1.6
`1.8
`1.8
`2.0
`1.6
`
`Figure 5. Time to FDA approval and percent approved by FDA for original NDA/BLA filings only. Data shown does not include
`supplemental applications.
`
`12 | BIO Industry Analysis
`
`Abraxis EX2016
`Apotex Inc. and Apotex Corp. v. Abraxis Bioscience, LLC
`IPR2018-00151; IPR2018-00152; IPR2018-00153
`
`

`

`Oncology and Non-Oncology Diseases
`
`Oncology drug development program transitions in the 2006-2015 period accounted for 31% of the 9,985 total transitions. With
`the lowest LOA from Phase I (5.1%, n=3,163), Oncology had an outsized effect on the overall industry success rate. To further
`understand this contribution, we compared phase transition success rates and LOA for non-oncology development programs
`against oncology development programs alone. Figure 6 shows Phase success rates and LOA from Phase I for oncology and
`non-oncology development programs. The LOA from Phase I across non-oncology indications was twice that for oncology alone,
`at 11.9% (n=6,822). Looking at individual phase transition success rates, it is clear that Phase III transition success rates were
`the reason Oncology ended up with the lowest overall success across our 14 disease categories. Oncology Phase III success
`was 23% lower than Non-Oncology disease areas.
`
`Probability of Success
`Oncology vs. Non-Oncology
`
`85.9%
`82.4%
`
`63.5%
`2.8%6
`
`63.7%
`
`40.1%
`
`34.3%
`24.6%
`
`Phase I to
`Phase II
`
`Phase III to
`Phase II to
`NDA/BLA
`Phase III
`Non-Oncology
`Oncology
`
`NDA/BLA to
`Approval
`
`11.9%
`5.1%
`
`Phase I to
`Approval
`
`100%
`90%
`80%
`70%
`60%
`50%
`40%
`30%
`20%
`10%
`0%
`
`Probability of Success
`
`Phase Success
`
`Phase I to Phase II
`
`Phase II to Phase III
`
`Phase III to NDA/BLA
`
`NDA/BLA to Approval
`
`Advanced or
`Suspended
`1222
`2360
`
`Phase
`Success
`62.8%
`63.5%
`
`Advanced or
`Suspended
`1416
`2446
`
`Phase
`Success
`24.6%
`34.3%
`
`Advanced or
`Suspended
`349
`1142
`
`Phase
`Success
`40.1%
`63.7%
`
`Advanced or
`Suspended
`176
`874
`
`Phase Success
`
`82.4%
`85.9%
`
`Oncology
`Non-Oncology
`
`Likelihood of Approval
`
`Phase I to Approval
`
`Phase II to Approval
`
`Phase III to Approval
`
`NDA/BLA to Approval
`
`Oncology
`Non-Oncology
`
`LOA n
`
`3163
`6822
`
`Phase LOA
`
`5.1%
`11.9%
`
`LOA n
`
`1941
`4462
`
`Phase LOA
`
`8.1%
`18.7%
`
`LOA n
`
`525
`2016
`
`Phase LOA
`
`LOA n
`
`Phase LOA
`
`33.0%
`54.7%
`
`176
`874
`
`82.4%
`85.9%
`
`Figure 6. Oncology vs. Non-Oncology phase transition success rates and LOA. Top: Chart of LOA from Phase I. Bottom: Table of phase
`transition success rates and LOA for Oncology vs. Non-Oncology indications, with corresponding n values. ‘Advanced or Suspended’
`refers to the total number of transitions used to calculate each success rate, with the n value noted in the text. The LOA n value is
`the total ‘Advanced or Suspended’ transitions of all phases used to calculate LOA. ‘Phase Success’ is the probability of successfully
`advancing to the next phase, whereas ‘Phase LOA’ is the probability of FDA approval for drugs in this phase of development.
`
`BIO Industry Analysis | 13
`
`Abraxis EX2016
`Apotex Inc. and Apotex Corp. v. Abraxis Bioscience, LLC
`IPR2018-00151; IPR2018-00152; IPR2018-00153
`
`

`

`Oncology Sub-Indication Phase Transition Success Rates and LOA
`
`Oncology drugs were further categorized into two main types of cancer: solid tumors and hematological cancers. Solid tumors
`had twice as many transitions in the data set (2,283 vs. 805), but only half the LOA from Phase I vs. hematological cancers (4.0%
`vs. 8.1%). These are shown in Figure 7 in more detail.
`
`0%
`
`10%
`
`Phase III Success Rate
`20%
`30%
`40%
`
`50%
`
`60%
`
`70%
`
`Oncology Indications
`Hematologic Cancers
`CLL/SLL - NHL
`Multiple Myeloma
`Indolent NHL
`AML
`Solid Tumors
`Renal Cell Cancer
`Breast Cancer
`Melanoma
`Prostate Cancer
`Colorectal Cancer
`NSCLC
`Ovarian Cancer
`Gastric Cancer
`Pancreatic Cancer
`
`Phase Success
`
`Phase I to Phase II
`
`Phase II to Phase III
`
`Phase III to NDA/BLA
`
`NDA/BLA to Approval
`
`Advanced or
`Suspended
`1222
`860
`327
`
`Phase Success
`
`62.8%
`64.1%
`61.8%
`
`Advanced or
`Suspended
`1416
`1055
`341
`
`Phase Success
`
`24.6%
`23.0%
`28.7%
`
`Advanced or
`Suspended
`349
`260
`78
`
`Phase Success
`
`40.1%
`34.2%
`52.6%
`
`Advanced or
`Suspended
`176
`108
`59
`
`Phase Success
`
`82.4%
`79.6%
`86.4%
`
`Oncology
`Solid
`Hematologic
`
`Likelihood of Approval
`
`Phase I to Approval
`
`Phase II to Approval
`
`Phase III to Approval
`
`NDA/BLA to Approval
`
`Oncology
`Solid
`Hematologic
`
`LOA n
`3163
`2283
`805
`
`Phase LOA
`5.1%
`4.0%
`8.1%
`
`LOA n
`1941
`1423
`478
`
`Phase LOA
`8.1%
`6.3%
`13.1%
`
`LOA n
`525
`368
`137
`
`Phase LOA
`33.0%
`27.3%
`45.4%
`
`LOA n
`176
`108
`59
`
`Phase LOA
`82.4%
`79.6%
`86.4%
`
`Figure 7. Phase transition success rates and LOA for Oncology indications with corresponding n values. ‘Advanced or Suspended’
`refers to the total number of transitions used to calculate each success rate, with the n value noted in the text. The LOA n value is
`the total ‘Advanced or Suspended’ transitions of all phases used to calculate LOA. ‘Phase Success’ is the probability of successfully
`advancing to the next phase, whereas ‘Phase LOA’ is the probability of FDA approval for drugs in this phase of development.
`
`14 | BIO Industry Analysis
`
`Abraxis EX2016
`Apotex Inc. and Apotex Corp. v. Abraxis Bioscience, LLC
`IPR2018-00151; IPR2018-00152; IPR2018-00153
`
`

`

`Phase II transition success rates by sub-indication tended to range close to the overall 25% Oncology calculation for Phase II, +/-10%.
`
`Narrowing in on Phase III transition success rates, only 34.2% of the 260 drug programs in solid tumor cancers were deemed
`sufficiently successful to file an NDA/BLA with the FDA. This was the underlying cause for the 2x difference we see in overall LOA,
`as the hematological cancer programs recorded a 52.6% success rate in Phase III. Since Phase III was identified as the weakest
`phase for Oncology, Phase III transition success rates for a number of major oncology sub-indications were included in Figure 7.
`
`The solid tumor Phase III transition success rate (34.2%, n=260) ended up as the lowest for any of the major disease categories
`studied. Solid tumor drugs for pancreatic cancer seemed to have the toughest challenges in Phase III studies (13.3%, n=15).
`However, Phase III success rates for Ovarian and Gastric cancers also fell below 30%.
`
`Hematological cancer Phase III transition success rates benefited from transition successes in CLL/SLL (66.7%, n=12) and
`MM (63.7%, n=11). ALL, Hodgkin’s and CML had Phase III success rates of 100% but only had fewer than five completed clinical
`development programs each (data not shown). Only AML (36.4%, n=11) came in below 40% for Phase III, which helped the overall
`hematologic cancer Phase III success rate remain above 50%.
`
`The NDA/BLA to approval success rate for all hematological cancers (86.4%, n=59) was impacted positively by Multiple Myeloma,
`ALL, and CML success, as each had more than five completed filings and 100% approval rates. The NDA/BLA success rate for
`all sold tumors was lower at 79.6% (n=108).
`
`Abbreviated cancer indications:
`
`ALL
`
`- Acute Lymphocytic Leukemia
`
`AML
`
`- Acute Myelogenous Leukemia
`
`CLL
`
`- Chronic Lymphocytic Leukemia
`
`CML
`
`- Chronic myelogenous Leukemia
`
`MM
`
`- Multiple Myeloma
`
`NHL
`
`- Non-Hodgkin’s Lymphoma
`
`NSCLC - Non-Small Cell Lung Cancer
`
`SLL
`
`- Small Lymphocytic Lymphoma
`
`BIO Industry Analysis | 15
`
`Abraxis EX2016
`Apotex Inc. and Apotex Corp. v. Abraxis Bioscience, LLC
`IPR2018-00151; IPR2018-00152; IPR2018-00153
`
`

`

`Rare Diseases and Chronic High Prevalence Diseases
`
`In recent years, there has been an increase in funding for companies focused on rare diseases.2 This is welcome news as there
`are reportedly 7,000 rare diseases and most do not have an approved therapeutic treatment.4 One question that is often asked
`is if the probabilities of success are any better for rare diseases, especially for those in which a particular defective gene has
`been confirmed as the sole contributor. On the other extreme, we have observed less venture funding for high prevalence,
`chronic diseases.2 The question we wanted to explore is whether investors may have scaled back funding because there is a
`higher hurdle to developing and gaining approval for medicines that treat highly prevalent conditions.
`
`Probability of Success
`Rare Disease and High Prevalence Diseases
`89%
`
`85% 87%
`
`76%
`
`63%
`58%
`
`73%
`
`61%
`
`58%
`
`50%
`
`30%
`
`%27
`
`25.3%
`
`9.6%
`8.7%
`
`Phase I to
`Phase II
`All Diseases
`
`Phase III to
`Phase II to
`NDA/BLA
`Phase III
`Chronic High Prevalence
`
`Phase I to
`NDA/BLA to
`Approval
`Approval
`Rare Diseases
`
`100%
`90%
`80%
`70%
`60%
`50%
`40%
`30%
`20%
`10%
`0%
`
`Probability of Success
`
`Phase Success
`
`Phase I to Phase II
`
`Phase II to Phase III
`
`Phase III to NDA/BLA
`
`NDA/BLA to Approval
`
`All Diseases
`Chronic High Prevalence
`Rare Diseases
`
`Advanced or
`Suspended
`3582
`732
`150
`
`Phase Success
`
`63.2%
`58.7