Olaratumab - Biologic Drug Details

Summary for olaratumab

Tradenames:	1
High Confidence Patents:	0
Applicants:	1
BLAs:	1
Recent Clinical Trials:	See clinical trials for olaratumab
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for olaratumab

Recent Clinical Trials for olaratumab

Identify potential brand extensions & biosimilar entrants

Sponsor	Phase
University of Miami	Phase 1
Janssen Scientific Affairs, LLC	Phase 1
Apexigen, Inc.	Phase 2

See all olaratumab clinical trials

Note on Biologic Patents

Matching patents to biologic drugs is far more complicated than for small-molecule drugs.

DrugPatentWatch employs three methods to identify biologic patents:

1. Brand-side disclosures in response to biosimilar applications

These patents were identified from disclosures by the brand-side company, in response to a potential biosimilar seeking to launch. They have a high certainty of blocking biosimilar entry. The expiration dates listed are not estimates — they're expiration dates as indicated by the brand-side company.

2. General brand-side disclosures

These patents were identified from searching drug labels and other general disclosures from the brand-side company. This list may exclude some of the patents which block biosimilar launch, and some of these patents listed may not actually block biosimilar launch. The expiration dates listed for these patents are estimates, based on the grant date of the patent.

3. Patents from broad patent text search

For completeness, these patents were identified by searching the patent literature for mentions of the branded or ingredient name of the drug. Some of these patents protect the original drug, whereas others may protect follow-on inventions or even inventions casually mentioning the drug. The expiration dates listed for these patents are estimates, based on the grant date of the patent.

1) High Certainty: US Patents for olaratumab Derived from Brand-Side Litigation

No patents found based on brand-side litigation

2) High Certainty: US Patents for olaratumab Derived from Company Disclosures

No patents found based on company disclosures

3) Low Certainty: US Patents for olaratumab Derived from Patent Text Search

No patents found based on company disclosures

Market Dynamics and Financial Trajectory of Olaratumab (LARTRUVO)

Introduction

Olaratumab, marketed as Lartruvo, is a human IgG1 monoclonal antibody developed by Eli Lilly and Company for the treatment of advanced soft tissue sarcoma (STS). Here, we delve into the market dynamics and financial trajectory of this drug, from its initial approval to its eventual withdrawal from the market.

Approval and Initial Market Entry

In October 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to olaratumab for the treatment of patients with STS not amenable to curative treatment with radiotherapy or surgery, and with a histologic subtype for which an anthracycline-containing regimen is appropriate[1].

Clinical Trial Data and Initial Efficacy

The approval was based on a randomized, active-controlled clinical trial involving 133 patients with metastatic STS. Patients receiving the combination of olaratumab and doxorubicin showed a statistically significant improvement in overall survival (OS) compared to those receiving doxorubicin alone, with a median OS of 26.5 months versus 14.7 months, respectively[1].

Market Reception and Sales

Following its approval, olaratumab saw significant sales. By the first quarter of 2019, the total worldwide sales of Lartruvo were $562 million[2]. However, the financial burden of the drug was substantial, with estimates suggesting a total financial burden to society of around $1 billion, despite questions about its efficacy[2].

Regulatory Designations and Expedited Programs

Olaratumab received several regulatory designations, including fast track, breakthrough therapy, priority review status, and accelerated approval. It also received orphan drug designation, reflecting its potential for treating a rare and serious condition[1].

Phase III ANNOUNCE Trial and Disappointing Results

The phase III ANNOUNCE trial, designed to confirm the clinical benefit of olaratumab in combination with doxorubicin, yielded disappointing results. The trial failed to meet its primary endpoint of overall survival, and there was no significant difference in OS between the combination arm and the doxorubicin alone arm. This led to a reevaluation of the drug's efficacy[4].

Withdrawal from the Market

In April 2019, Eli Lilly announced the withdrawal of olaratumab from the market for the treatment of advanced STS, following the negative findings of the ANNOUNCE trial. The FDA and the European Medicines Agency (EMA) recommended against treating new patients with the combination of olaratumab and doxorubicin, although patients already benefiting from the treatment could continue under certain conditions[4].

Financial Impact of Withdrawal

The withdrawal had significant financial implications. Despite the initial sales, the lack of efficacy and subsequent market withdrawal led to a substantial financial loss for Eli Lilly. The total financial burden, including sales and the cost of development, was estimated to be around $1 billion, highlighting the financial risks associated with drug development and market approval[2].

Access Program for Existing Patients

To support patients currently on olaratumab, Eli Lilly established an access program. This program allowed patients to continue their treatment, subject to local laws and regulations, ensuring minimal disruption to their care[4].

Side Effects and Safety Profile

Olaratumab's safety profile included common side effects such as nausea, fatigue, neutropenia, musculoskeletal pain, and infusion-related reactions. These side effects were a consideration in the overall risk-benefit assessment of the drug[1].

Pharmacokinetics and Systems Pharmacology

Studies on the pharmacokinetics and systems pharmacology of olaratumab provided insights into its distribution, metabolism, and excretion. However, these did not alter the drug's fate given the clinical trial outcomes[3].

Industry Expert Insights

Industry experts, such as Jaap Verweij, MD, PhD, highlighted the financial and clinical implications of olaratumab's rise and fall. The drug's failure to demonstrate efficacy in a confirmatory trial underscored the challenges and risks in drug development[2].

Key Takeaways

• Accelerated Approval and Initial Success: Olaratumab was approved under accelerated approval programs based on promising initial trial data.
• Disappointing Phase III Results: The ANNOUNCE trial failed to confirm the clinical benefit, leading to market withdrawal.
• Financial Burden: The total financial impact, including sales and development costs, was estimated at around $1 billion.
• Access Program: Existing patients were allowed to continue treatment under an access program.
• Regulatory Recommendations: FDA and EMA advised against treating new patients with the combination of olaratumab and doxorubicin.

FAQs

What was the basis for the FDA's accelerated approval of olaratumab?

The FDA granted accelerated approval based on data from a randomized, active-controlled clinical trial involving 133 patients with metastatic STS, showing improved overall survival with the combination of olaratumab and doxorubicin[1].

Why was olaratumab withdrawn from the market?

Olaratumab was withdrawn due to the disappointing results of the phase III ANNOUNCE trial, which failed to confirm the clinical benefit of the drug in combination with doxorubicin[4].

What were the common side effects associated with olaratumab?

Common side effects included nausea, fatigue, neutropenia, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache[1].

How did the market react to olaratumab's initial approval?

The drug saw significant sales, with total worldwide sales reaching $562 million by the first quarter of 2019. However, the financial burden was substantial, estimated at around $1 billion[2].

What measures were taken to support patients already on olaratumab after its market withdrawal?

Eli Lilly established an access program to allow patients currently benefiting from olaratumab to continue their treatment with minimal interruption, subject to local laws and regulations[4].

What regulatory designations did olaratumab receive?

Olaratumab received fast track, breakthrough therapy, priority review status, accelerated approval, and orphan drug designation[1].

Sources

1. FDA: Olaratumab (LARTRUVO) - FDA
2. Cancer Therapy Advisor: The Accelerated Rise and Fall of Olaratumab in Sarcoma
3. ResearchGate: Pharmacokinetics and systems pharmacology of monoclonal antibody olaratumab for inoperable soft tissue sarcoma
4. OncLive: Olaratumab to Be Withdrawn From Market, Access Program Planned in Soft Tissue Sarcoma

Last updated: 2024-12-18