The FDA’s 505(b)(2) pathway is a game-changer, offering a more efficient route to market for improved versions of existing drugs while ensuring they meet stringent safety and efficacy standards. This pathway strikes a balance between the lengthy process of discovering new molecules and the straightforward approach of making generic drugs, allowing companies to bring innovative products to market that address unresolved unmet needs.
While many 505(b)(2) products have entered the market, success stories are varied. Key factors influencing the success of a 505(b)(2) product include thorough market research to identify unmet needs, robust IP strategies, targeted marketing plans, and clear commercial strategies.
Here are 10 noteworthy 505(b)(2) launches from the past decade, each achieving peak sales between $100M and $500M. These products stood out due to their unique market offerings and innovative use of technology to meet unmet needs:
1. ONIVYDE (Irinotecan HCl), Liposomal IV injection
Approval: Oct 22, 2015
Applicant: Ipsen Biopharmaceuticals
Indication: for treatment of metastatic pancreatic adenocarcinoma (different indication than RLD)
Submission classification: Type 5 – New Formulation or New Manufacturer
Technology: Pegylated liposomal formulation
RLD: Camptosar injection (metastatic carcinoma of the colon or rectum)
Clinical path:
1 single, multi-center, randomized, open-label, active controlled, three-arm trial (NAPOLI) enrolling 417 patients with metastatic pancreatic adenocarcinoma and PK data from few trials
Value addition:
- Protects irinotecan from being rapidly cleared from the body, results in prolonged circulation time
- Delivers its cytotoxic payload to the tumor directly
- Conversion to SN-38, its more potent active metabolite at site of action
- Address the challenge of the dense stroma in pancreatic tumor
Peak sales: $140 M
2. VALTOCO (Diazepam), Nasal Spray
Approval: Jan 10, 2020
Applicant: Neurelis Inc.
Indication: for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) in 6 years of age & older
Submission classification: Type 3 – New Dosage Form
Technology: Drug-device product based on Intravail® technology which increases drug absorption across the nasal mucosa
RLD: Diastat rectal gel
Clinical path:
1 open-label, PK and safety study during ictal/peri-ictal and interictal periods and 1 multicenter, open-label, single-arm chronic safety study of Valtoco who used Valtoco as needed to control bouts of uncontrolled seizures (seizure clusters or ARS) over at least a 6-month period
Value addition:
- On hand rescue treatment for episodes of frequent seizure activity
- Portable device, Ready to use
- Individualized dosing
Peak sales: $142 M
3. SUBLOCADE (Buprenorphine), SC Extended release Injection
Approval: Nov 30, 2017
Applicant: Indivior Inc
Indication: for the treatment of moderate to severe opioid use disorder (OUD)
Submission classification: Type 3 – New Dosage Form
Technology: Atrigel technology – forms in situ gel/depot for sustained release of drug for 1 month
RLD: Subutex sublingual tablet
Clinical path:
1 inpatient opioid blockade study (RB-US-13-0002) and 1 randomized, double-blind, placebo-control efficacy, safety study (RBUS-13-001)
Value addition:
- Sustains the therapeutic level of buprenorphine in the blood throughout the month. No real daily ups and downs
- Blocks the rewarding effects of opioids, which are the “pleasurable feelings” that can keep people using
Peak sales: $143 M
4. JORNAY PM (Methylphenidate HCl), Extended release Capsule
Approval: Aug 8, 2018
Applicant: Ironshore Pharma
Indication: treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older
Submission classification: Type 3 – New Dosage Form
Technology: DR and ER beads to provide controlled release during day time
RLD: Ritalin IR tablet
Clinical path:
2 Phase III (Safety & efficacy) studies & few Phase I BA, food effect studies
Value addition:
- JORNAY PM is the first and only ADHD treatment with once-nightly dosing.
- It allows control over ADHD symptoms in children during the early morning routine, which remains a significant concern for parents.
- It is given in evening whereas other ADHD extended release products are given in morning.
Peak sales: $182M
5. XYOSTED (Testosterone Enanthate), Subcutaneous Autoinjector
Approval: Sep 28, 2018
Applicant: Antares Pharma
Indication: Indicated for testosterone replacement therapy in adult males with hypogonadism
Submission classification: Type 3 – New Dosage Form
Technology: Autoinjector based on VIBEX platform
RLD: Delatestryl injection
Clinical path:
3 short-term Phase 1 and Phase 2 studies and 2 long-term, Phase 3 safety and efficacy studies
Value addition:
- Patient convenience with self-administration
- Less painful compared to available IM injection
- No risk of transference
Peak sales: $186 M
6. CINVANTI (Aprepitant), Intravenous emulsion
Approval: Nov 9, 2017
Applicant: Heron Therapeutics Inc
Indications:
- acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC)
- delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC)
- nausea and vomiting associated with initial and repeat courses of MEC as a 3-day regimen
Submission classification: Type 3 – New Dosage Form
Technology: oil-in-water emulsion with improved solubility of aprepitant
RLD: Emend (fosaprepitant) for injection
Clinical path:
2 Bioavailability studies
Value addition:
- Unique synthetic–surfactant-free formulation administered as IV Push or IV infusion
- 2-minute IV push saves $1.99 per push and 33 minutes time when compared to 30 minutes infusion
Peak sales: $187 M
7. XHANCE (Fluticasone propionate), Nasal Spray
Approval: Sep 18, 2017
Applicant: Optinose US Inc
Indication: for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) in adults
Submission classification: Type 5 – New Formulation or New Manufacturer
Technology: Breath Powdered Exhalation Delivery System (Device)
RLD: Flovent HFA Aerosol Inhalation, Flonase Nasal spray
Clinical path:
2 efficacy and safety studies and 2 open label safety studies along with and BA study
Value addition:
- It is drug-device combination product that uses the Exhalation Delivery System™ (also referred to as the EDS®) designed to deliver a topical steroid to the high and deep regions of the nasal cavity where sinuses ventilate and drain and where standard nasal sprays usually do not reach.
Peak sales: $197 M
8. RYTARY (Carbidopa & Levodopa), Extended-release capsule
Approval: Jan 7, 2015
Applicant: Impax Laboratories LLC
Indication: for the treatment of Parkinson’s disease, post-encephalitic parkinsonism, and parkinsonism that may follow carbon monoxide intoxication or manganese intoxication
Submission classification: Type 5 – New Formulation or New Manufacturer
Technology: IR and ER beads designed to provide release at different rates within the stomach and the intestine
RLD: Sinemet tablet, Sinemet CR tablet & Stalevo tablet
Clinical path:
2 randomized Phase III studies & 6 additional studies such PK, food effect, BA
Value addition:
- Consistent PK profile to reduce motor fluctuations along with reduction in dosing frequency
- To reduce the amount of time during the day when patients symptoms are not adequately controlled
- The daily “off-time” improved by over an hour each day in the extended release formulation
Peak sales: $274 M
9. BELBUCA (Buprenorphine HCl), Buccal film
Approval: Oct 23, 2015
Applicant: Biodelivery Sciences International Inc.
Indication: for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate
Submission classification: Type 3 – New Dosage Form
Technology: BioErodable MucoAdhesive (BEMA) technology
RLD: Buprenex injection & Subutex sublingual tablet
Clinical path:
Because the reference products, Buprenex and Subutex are approved for different indications than Belbuca, the Applicant was required to provide evidence of efficacy and safety to support the proposed indication. The Applicant submitted the results of two adequate and well-controlled efficacy studies, additional safety data from open-label safety studies along with PK studies.
Value addition:
- Film adheres to the buccal mucosa better and erode in a matter of minute
- Convenient, rapid-onset opioid pain reliever with limited abuse liability
- Avoids poor oral bioavailability due to extensive first pass metabolism
- Provides rapid delivery and titration over a greater range of doses compared to previous transdermal therapy. (0.075MG; 0.15MG; 0.3MG; 0.45MG; 0.6MG; 0.75MG; 0.9MG )
Peak sales: $317 M
10. ARISTADA (Aripiprazole Lauroxil), Intra-muscular; extended-release suspension
Approval: Oct 05, 2015
Applicant: Alkermes Inc
Indication: for the treatment of schizophrenia in adults
Submission classification: Type 1 – New Molecular Entity
Technology: Nanocrystal technology
RLD: Abilify tablets
Clinical path:
Applicant submitted 1 Phase III (safety and efficacy) clinical study, along with single and multiple dose Phase I PK studies. The Agency’s previous finding of safety and efficacy from oral aripiprazole tablets was considered as evidence.
Value addition:
- First Long-Acting Atypical Antipsychotic with Both Once-Monthly and Six-Week Dosing Options
- Range of dose strengths and dosing interval options, are designed to address the individual needs of patients (441MG/1.6ML; 662MG/2.4ML; 882MG/3.2ML; 1064MG/3.9ML)
Peak sales: $425 M
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