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39482711000001104

New Medicines

Retsevmo (UK/EU), Retevmo (US) Advanced RET mutant medullary thyroid cancer - second-line monotherapy

Information

Retsevmo (UK/EU), Retevmo (US)
New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

Launched
Approved (Licensed)
Launched
November 2021
Yes
Nov 21Available in the UK. Price for 60 x 40mg capsules £2,340 and 80mg capsules £4,680 [16].
Feb 21Approved in EU [15].
Feb 21Approved in UK by MHRA for use as monotherapy in the treatment of adults with advanced RET fusion-positive NSCLC who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy, or advanced RET fusion-positive thyroid cancer who require systemic therapy following prior treatment with sorafenib and/or lenvatinib. Also for use as monotherapy in the treatment of adults and adolescents 12 years and older with advanced RET-mutant medullary thyroid cancer (MTC) who require systemic therapy following prior treatment with cabozantinib and/or vandetanib [14].
Dec 20Recommended for conditional EU approval by CHMP - the full indication is, as monotherapy, "for the treatment of adults with: advanced RET fusion-positive non-small cell lung cancer (NSCLC) who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy; advanced RET fusion-positive thyroid cancer who require systemic therapy following prior treatment with sorafenib and/or lenvatinib; and for the treatment of adults and adolescents 12 years and older with advanced RET mutant medullary thyroid cancer (MTC) who require systemic therapy following prior treatment with cabozantinib and/or vandetanib." Conditional approval allows products to be approved before the full data normally required are available; approval must be renewed annually, and the company has a timescale to produce the comprehensive data required for a full authorisation [13].
Jun 20Has orphan drug status in US for treatment of RET-fusion-positive NSCLC [13].
May 20Launched in the US with a list price of about $20,600 for a 30-day supply [12].
May 20Approved in US. [10]
May 20Approved in US [10]
Feb 20Currently pre-registration in EU. Has been filed using the EU centralised procedure [8].
Jan 20FDA priority review awarded, so expect Q3 2020 decision on licensing approval [6].
Aug 19Has breakthrough therapy status in US [4].

Category

A highly selective, adenosine triphosphate -competitive small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase (RTK).
There are around 3,500 new thyroid cancer cases in the UK every year [1]. MTC accounts for approximately 5-8% of all thyroid cancer. Clinically, MTC is mainly sporadic (70-80%), but hereditary pattern is present in 20-30% of cases, transmitted as an autosomal dominant trait. Somatic RET mutations can be detected in tumour tissue of 40-60% of sporadic MTC patients [2].
Advanced RET mutant medullary thyroid cancer - second-line monotherapy
Oral

Further information

Yes

Trial or other data

May 20Approval in the US is based on results of the LIBRETTO-001 trial (NCT03157128) in which patients received 160mg selpercatinib orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). The study enrolled 143 patients aged 12 years of age and older with advanced or metastatic RET-mutant MTC who had been previously treated with cabozantinib, vandetanib or both (types of chemotherapy), and patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for the 55 previously treated patients was 69%. For 76% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in 88 patients who had not been previously treated with an approved therapy for MTC. The ORR for these patients was 73%. For 61% of patients who had a response to the treatment, their response lasted at least 6 months [11].
Feb 20 PIII LIBRETTO-531 (NCT04211337) will recruit patients in countries around the world, including the US, EU & UK. Collection of primary outcome data (Treatment Failure-Free Survival ) is due to complete Feb 23 [9]
Jan 20PIII trial LIBRETTO-531 starts, in patients with treatment-naïve RET-mutant MTC. The trial will enrol 400 patients with advanced or metastatic RET-mutant MTC who have received no prior systemic therapy for metastatic disease and compare selpercatinib with cabozantinib or vandetanib as initial treatment [7].
Oct 19Lilly reported LIBRETTO-001 data from 76 patients who had not received any kind of cancer treatment and 26 “heavily pretreated” patients in which selpercatinib shrank tumors in 59% of patients in the 1st group and 62% of patients in the 2nd group. Patients were followed up for 6 months [5].
Sep 19PI/II LIBRETTO-001 study is recruiting [3].
May 17PI/II LIBRETTO-001 study to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of LOXO-292 administered orally to patients with advanced solid tumors, including RET-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation starts (NCT03157128). 970 adults and children aged 12 years or older will be recruited from sites including the US, EU & UK. Collection of primary outcome data is due to complete Mar 22 [3].

Evidence based evaluations

Retsevmo (UK/EU), Retevmo (US) Advanced RET fusion-positive non-small cell lung cancer (NSCLC) - second-line monotherapy

Information

Retsevmo (UK/EU), Retevmo (US)
New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

Launched
Approved (Licensed)
Launched
November 2021
Yes
Sep 22FDA approves selpercatinib for use in adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a RET gene fusion, as detected by an FDA-approved test. This FDA action broadens the Retevmo label to include patients with locally advanced disease and converts the May 2020 accelerated approval for NSCLC to a traditional approval. Approval is supported by data from the pivotal LIBRETTO-001 trial [18].
Nov 21Available in the UK. Price for 60 x 40mg capsules £2,340 and 80mg capsules £4,680 [17].
Feb 21Approved in EU [16].
Feb 21Approved in UK by MHRA for use as monotherapy in the treatment of adults with advanced RET fusion-positive NSCLC who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy, or advanced RET fusion-positive thyroid cancer who require systemic therapy following prior treatment with sorafenib and/or lenvatinib. Also for use as monotherapy in the treatment of adults and adolescents 12 years and older with advanced RET-mutant medullary thyroid cancer (MTC) who require systemic therapy following prior treatment with cabozantinib and/or vandetanib [15].
Dec 20Recommended for conditional EU approval by CHMP - the full indication is, as monotherapy, "for the treatment of adults with: advanced RET fusion-positive non-small cell lung cancer (NSCLC) who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy; advanced RET fusion-positive thyroid cancer who require systemic therapy following prior treatment with sorafenib and/or lenvatinib; and for the treatment of adults and adolescents 12 years and older with advanced RET mutant medullary thyroid cancer (MTC) who require systemic therapy following prior treatment with cabozantinib and/or vandetanib." Conditional approval allows products to be approved before the full data normally required are available; approval must be renewed annually, and the company has a timescale to produce the comprehensive data required for a full authorisation [14].
May 20Approved in US. [10]
May 20Launched in the US priced at $20,600 for a 30-day supply [12].
Feb 20Currently pre-registration in EU. Has been filed using centralised procedure [8].
Jan 20FDA priority review awarded, so expect Q3 2020 decision on licensing approval [6].
Sep 19Loxo Oncology is now owned by Eli Lilly. US filing planned before the end of 2019 [5].
Aug 19Has breakthrough therapy status in US [4].

Category

A highly selective, adenosine triphosphate -competitive small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase (RTK), first-in-class.
During 2011 there were 43,463 new cases of lung cancer in the UK, an incidence rate of 48.5 per 100,000 persons. Prevalence increased by 10% between 2008 and 2012. Stable incidence and rising prevalence point to improving lung cancer survival rates [1]. EGFR, ALK, and ROS1 are 3 major driver genes that play an important role in lung cancer development and precision management. RET rearrangement is detected in 1% to 2% of cases [2].
Advanced RET fusion-positive non-small cell lung cancer (NSCLC) - second-line monotherapy
Oral

Further information

Yes

Trial or other data

May 20FDA approval was based on results of the LIBRETTO-001 trial. During the trial, patients received 160 mg selpercatinib (Retevmo) orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR for the 105 patients was 64%. For 81% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had never undergone treatment. The ORR for these patients was 84%. For 58% of patients who had a response to the treatment, their response lasted at least 6 months [11].
Feb 20PIII LIBRETTO-431 study (NCT04194944) is recruiting in countries around the world including the US, EU & UK. Collection of primary outcome data (progression-free survival) is due to complete Dec 23 [9].
Jan 20PIII trial LIBRETTO-431 starts in treatment-naïve RET fusion-positive NSCLC. The trial will enroll 400 patients with advanced or metastatic RET fusion-positive NSCLC who have received no prior systemic therapy for metastatic disease [7].
Sep 19New data from PI/II LIBRETTO-001 study reported at the World Conference on Lung Cancer. Selpercatinib showed a 68% objective response rate (ORR) in heavily pretreated RET fusion-positive non-small cell lung cancer (NSCLC). Nine patients (1.7%) stopped treatment as a result of toxicity out of more than 500 across the study [5].
Sep 19PI/II LIBRETTO-001 study is recruiting [3].
May 17PI/II LIBRETTO-001 study to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of LOXO-292 administered orally to patients with advanced solid tumors, including RET-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation starts (NCT03157128). 970 adults and children aged 12 years or older will be recruited from sites including the US, EU & UK. Collection of primary outcome data is due to complete Mar 22 [3].

Evidence based evaluations

Retsevmo (UK/EU), Retevmo (US) Advanced RET fusion-positive thyroid cancer - second-line monotherapy

Information

Retsevmo (UK/EU), Retevmo (US)
New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

Launched
Approved (Licensed)
Launched
November 2021
Yes
Nov 21Available in the UK. Price for 60 x 40mg capsules £2,340 and 80mg capsules £4,680 [11].
Feb 21Approved in EU [10].
Feb 21Approved in UK by MHRA for use as monotherapy in the treatment of adults with advanced RET fusion-positive NSCLC who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy, or advanced RET fusion-positive thyroid cancer who require systemic therapy following prior treatment with sorafenib and/or lenvatinib. Also for use as monotherapy in the treatment of adults and adolescents 12 years and older with advanced RET-mutant medullary thyroid cancer (MTC) who require systemic therapy following prior treatment with cabozantinib and/or vandetanib [9].
Dec 20Recommended for conditional EU approval by CHMP - the full indication is, as monotherapy, "for the treatment of adults with: advanced RET fusion-positive non-small cell lung cancer (NSCLC) who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy; advanced RET fusion-positive thyroid cancer who require systemic therapy following prior treatment with sorafenib and/or lenvatinib; and for the treatment of adults and adolescents 12 years and older with advanced RET mutant medullary thyroid cancer (MTC) who require systemic therapy following prior treatment with cabozantinib and/or vandetanib." Conditional approval allows products to be approved before the full data normally required are available; approval must be renewed annually, and the company has a timescale to produce the comprehensive data required for a full authorisation [8].
May 20Launched in the US with a list price of about $20,600 for a 30-day supply [6]
May 20Approved in the US [5].
Feb 20Currently pre-registration in EU. Has been filed using the EU centralised procedure [7].
Nov 19Granted orphan therapy status in the US for the treatment of RET fusion-positive or RET mutant thyroid cancers including poorly differentiated thyroid cancer, undifferentiated or anaplastic thyroid cancer, medullary thyroid cancer, and locally advanced or metastatic follicular or papillary thyroid cancer [4].
Aug 19Has breakthrough therapy status in the US [3].

Category

A highly selective, adenosine triphosphate -competitive small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase (RTK).
There are around 3,500 new thyroid cancer cases in the UK every year [1]. MTC accounts for approximately 5-8% of all thyroid cancer. Clinically, MTC is mainly sporadic (70-80%), but hereditary pattern is present in 20-30% of cases, transmitted as an autosomal dominant trait. Somatic RET mutations can be detected in tumour tissue of 40-60% of sporadic MTC patients [2].
Advanced RET fusion-positive thyroid cancer - second-line monotherapy
Oral

Further information

Yes

Trial or other data

May 20US approval based on the results of the PI/II LIBRETTO-001 clinical trial (EudraCT2017-000800-59; NCT03157128) in which patients received 160 mg selpercatinib orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). Efficacy for RET fusion-positive thyroid cancer was evaluated in adults and pediatric patients 12 years of age and older. The study enrolled 19 patients with RET fusion-positive thyroid cancer who were radioactive iodine-refractory (RAI, if an appropriate treatment option) and had received another prior systemic treatment, and eight patients with RET fusion-positive thyroid cancer who were RAI-refractory and had not received any additional therapy. The ORR for the 19 previously treated patients was 79%. For 87% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in eight patients who had not received therapy other than RAI. The ORR for these patients was 100%. For 75% of patients who had a response to the treatment, their response lasted at least 6 months [5].

Evidence based evaluations

Retsevmo (UK/EU), Retevmo (US) Advanced RET fusion-positive non-small cell lung cancer (NSCLC) - first-line monotherapy

Information

Retsevmo (UK/EU), Retevmo (US)
Licence extension / variation
Eli Lilly
Eli LIlly

Development and Regulatory status

Phase III Clinical Trials
Recommended for approval (Positive opinion)
Launched
Sep 22FDA approves selpercatinib for use in adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a RET gene fusion, as detected by an FDA-approved test. Approval is supported by data from the pivotal LIBRETTO-001 trial [7,8].
Apr 22Recommended for EU approval by CHMP – the extension to the existing indication is for “treatment of adults with advanced RET fusion positive non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor” (previously licensed only for use following prior treatment with immunotherapy and/or platinum-based chemotherapy) [6].
Dec 21Currently pre-registration in EU for an extension of indication to include the first-line treatment of RET fusion-positive NSCLC. The proposed indication is based on the results from PI/II LIBRETTO-001 study [5].

Category

A highly selective, adenosine triphosphate -competitive small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase (RTK), first-in-class.
During 2011 there were 43,463 new cases of lung cancer in the UK, an incidence rate of 48.5 per 100,000 persons. Prevalence increased by 10% between 2008 and 2012. Stable incidence and rising prevalence point to improving lung cancer survival rates [1]. EGFR, ALK, and ROS1 are 3 major driver genes that play an important role in lung cancer development and precision management. RET rearrangement is detected in 1% to 2% of cases [2].
Advanced RET fusion-positive non-small cell lung cancer (NSCLC) - first-line monotherapy
Oral

Further information

Yes

Trial or other data

Dec 21Estimated primary completion date of PIII LIBRETTO-431 study is Jan 23 [4].
Aug 21PIII LIBRETTO-431 study is recruiting [3].
Feb 20PIII LIBRETTO-431 study to assess if selpercatinib compared to a standard treatment is effective and safe in participants with rearranged during transfection (RET) fusion-positive non-squamous non-small cell lung cancer (NSCLC) that has spread to other parts of the body starts (NCT04194944). 250 adults will be recruited from sites including in the UK and rest of Europe. Patients will be randomised to selpercatinib monotherapy, or pemetrexed IV plus investigator discretion of carboplatin IV or cisplatin IV with or without pembrolizumab IV, Primary outcome is progression-free survival; collection of these data is due to complete Jan 23 [3].

Evidence based evaluations

Retsevmo (UK/EU), Retevmo (US) Advanced RET mutant medullary thyroid cancer - first-line monotherapy

Information

Retsevmo (UK/EU), Retevmo (US)
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Phase III Clinical Trials
Recommended for approval (Positive opinion)
Phase III Clinical Trials
Yes
Jul 22EU positive opinion granted recommending a licence change to include use as first-line monotherapy for advanced RET mutant medullary thyroid cancer. The proposed new indication is “Retsevmo as monotherapy is indicated for the treatment of adults and adolescents 12 years and older with advanced RET mutant medullary thyroid cancer (MTC)” [6].
Apr 22Filed in EU [5].
May 20Has orphan drug status in US [4].

Category

A highly selective, adenosine triphosphate -competitive small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase (RTK).
There are around 3,500 new thyroid cancer cases in the UK every year [1]. MTC accounts for approximately 5-8% of all thyroid cancer. Clinically, MTC is mainly sporadic (70-80%), but hereditary pattern is present in 20-30% of cases, transmitted as an autosomal dominant trait. Somatic RET mutations can be detected in tumour tissue of 40-60% of sporadic MTC patients [2].
Advanced RET mutant medullary thyroid cancer - first-line monotherapy
Oral

Trial or other data

Aug 21PIII LIBRETTO-531 is recruiting and now due to complete collection of primary outcome data in May 24 [3].
Feb 20PIII LIBRETTO-531 to assess if selpercatinib is safe and more effective compared to a standard treatment in treatment-naive participants with rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or has spread to other parts of the body starts (NCT04211337). It will recruit 400 patients aged 12 years and older in countries around the world, including the US, EU & UK. Collection of primary outcome data (treatment failure-free survival ) is due to complete Feb 23 [3].

Retsevmo (UK/EU), Retevmo (US) Advanced solid tumours with a RET gene fusion in adults that have progressed on/after prior systemic treatment or who have no other options

Information

Retsevmo (UK/EU), Retevmo (US)
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Sep 22FDA approves a new indication for selpercatinib to treat adults with locally advanced or metastatic solid tumours with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on ORR and duration of response (DOR), and is supported by data from the pivotal LIBRETTO-001 trial [1,2].

Category

A highly selective, adenosine triphosphate -competitive small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase (RTK).
Variable depending on tumour type. RET cancers are rare, though occurring predominantly in non-small cell lung cancer (NSCLC) and thyroid cancers [1].
Advanced solid tumours with a RET gene fusion in adults that have progressed on/after prior systemic treatment or who have no other options
Oral

Trial or other data

Sep 22In the Libretto-001 trial, among the 41 patients in the tumour-agnostic data set, the most common cancers were pancreatic adenocarcinoma (27%), colorectal (24%), salivary (10%), and unknown primary (7%). Thirty-seven patients (90%) received prior systemic therapy (median 2 [range 0 – 9]; 32% received 3 or more). Overall response rate was 44% and median duration of response 24.5 months. 67% had a duration of response of 6 months or longer. ORR was 55% in patients with pancreatic adenocarcinoma, 20% in colorectal cancer, 50% in salivary and 33% in those with an unknown primary [2].

Retsevmo (UK/EU), Retevmo (US) Early-stage Ib-IIIa RET-positive non-small cell lung cancer (NSCLC) - adjuvant therapy

Information

Retsevmo (UK/EU), Retevmo (US)
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

A highly selective, adenosine triphosphate -competitive small molecule inhibitor of the rearranged during transfection (RET) receptor tyrosine kinase (RTK), first-in-class.
There are around 48,000 new lung cancer cases and 35,000 deaths from lung cancer in the UK every year. The majority of lung cancers are diagnosed at an advanced stage, when the cancer has spread to lymph nodes and other organs in the chest (locally advanced disease; stage III) or to other parts of the body (metastatic disease; stage IV). Up to 85% of lung cancers are NSCLC [1].
Early-stage Ib-IIIa RET-positive non-small cell lung cancer (NSCLC) - adjuvant therapy
Oral