Notice of Compliance with Conditions granted for Retevmo™ (selpercatinib), the first therapy in Canada specifically for patients with advanced RET-driven lung and thyroid cancers Français
- Approved for metastatic RET fusion-positive non-small cell lung cancer, advanced or metastatic RET-mutant medullary thyroid cancer and advanced or metastatic RET fusion-positive thyroid cancer
- Conditional marketing authorization based on data from LIBRETTO-001 Phase 1/2, the largest trial ever reported in patients with RET-driven cancers
- Registrational data demonstrated durable objective responses and showed high intracranial response rate in patients with non-small cell lung cancer that has spread to the brain
TORONTO, June 21, 2021 /CNW/ - On June 15, 2021, Health Canada issued a Notice of Compliance with Conditions (NOC/c) for Retevmo™ (selpercatinib). Retevmo is indicated as monotherapy for the treatment of:
- metastatic RET fusion-positive non-small cell lung cancer (NSCLC) in adult patients,
- RET-mutant medullary thyroid cancer (MTC) in adult and pediatric patients 12 years of age and older with unresectable advanced or metastatic disease,
- RET fusion-positive differentiated thyroid carcinoma in adult patients with advanced or metastatic disease (not amenable to surgery or radioactive iodine therapy) following prior treatment with sorafenib and/or lenvatinib.1
Retevmo received conditional marketing authorization based on the LIBRETTO-001 Phase 1/2 trial, under Health Canada's NOC/c policy. This policy facilitates earlier access to new drugs for serious, life-threatening or severely debilitating illnesses on the basis of promising evidence of clinical effectiveness. Conditional marketing authorization under this policy is granted on the condition that additional clinical trials be conducted to verify the anticipated benefit. Two confirmatory Phase 3 trials are underway to further verify the clinical benefit of Retevmo.
"We are very pleased by the conditional marketing authorization of Retevmo for a patient population facing a significant unmet need in Canada," says Dr. Doron Sagman, vice president, R&D and Medical Affairs, Eli Lilly Canada. "Findings from the LIBRETTO-001 trial reinforce the importance of precision medicine and provide an opportunity to help a population of patients with specifically identifiable disease."
The efficacy of Retevmo in patients with advanced RET fusion-positive NSCLC, RET-mutant MTC, and RET fusion-positive thyroid cancer was evaluated in a phase 1/2, multicenter, open-label, multi-cohort clinical trial (LIBRETTO-001, N=702). The trial enrolled both treatment-naive patients and heavily pre-treated patients with a variety of advanced solid tumors including RET fusion positive NSCLC, RET-mutant MTC, RET fusion-positive thyroid cancer, and certain other solid tumors with RET alterations. Major efficacy outcomes were overall response rate (ORR) and duration of response (DoR) and were assessed by a blinded independent review committee. Prespecified secondary endpoints included central nervous system (CNS) ORR and CNS DoR.
RET Fusion-Positive NSCLC |
RET-Mutant MTC |
RET Fusion-Positive Thyroid Cancers |
|||
Systemic Treatment Naïve |
Treatment Experienced |
Cabozantinib |
Cabozantinib |
Treatment Experienced |
|
No. of patients |
39 |
105 |
88 |
55 |
19 |
ORR (95% CI) |
85 (70, 94) |
64 (54, 73) |
73 (62, 82) |
69 (55, 81) |
79 (54, 94) |
Median DoR, months (95% CI) |
17.5 (12, NE) |
18.4 (7.6, NE) |
|||
NE=Not estimable CI=confidence interval Thyroid cancers include: papillary, Hurthle cell, anaplastic, and poorly differentiated |
Among previously treated NSCLC patients with measurable brain metastases, 10 out of 11 patients observed intracranial responses (CNS ORR).
In the LIBRETTO-001 trial, there was a five per cent discontinuation rate due to adverse reactions (ARs). The most common ARs, including laboratory abnormalities (≥25 percent), were increased AST, increased ALT, decreased lymphocyte count, increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, increased creatinine, diarrhea, increased alkaline phosphatase, hypertension, decreased platelets, increased total cholesterol, fatigue, rash, decreased sodium and constipation. In addition, the most frequent serious AR (≥ 2 per cent) were pneumonia and hemorrhage.
"This announcement from Health Canada provides new hope for Canadians with lung cancer. Selpercatinib treatment leads to dramatic benefits for patients with RET-driven cancers, including those with cancer that has spread to the brain. The future for people with lung cancer in Canada is getting brighter every year," says Natasha Leighl, medical oncologist, Princess Margaret Cancer Centre.
"We are encouraged by the conditional marketing authorization of selpercatinib for patients with metastatic RET fusion-positive non-small cell lung cancer. Testing is a critical part of personalized medicine. We hope provinces include RET alterations in their testing strategies so that patients and their physicians can make appropriate treatment decisions," says Shem Singh, executive director, Lung Cancer Canada.
"Most medullary thyroid cancers result from RET alterations, as do a portion of other thyroid cancers. A treatment option like Retevmo, which has the ability to safely and effectively inhibit RET, makes it an important treatment consideration for people with RET-driven cancers," says Dr. Monika Krzyzanowska, MD MPH FRCPC FASCO.
"People who are living with thyroid cancer don't have time to wait and see what works. Precision medicine is the future of healthcare," says Sarah Eadie, president, Thyroid Cancer Canada. "Early RET testing is the first step to better patient outcomes. We are happy to learn of this conditional marketing authorization for Retevmo."
About Retevmo™ (selpercatinib)
Retevmo (selpercatinib, formerly known as LOXO-292) (pronounced reh-TEHV-moh) is a selective and potent RET kinase inhibitor. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. Retevmo is an oral prescription medicine dosed at 120 mg or 160 mg dependent on weight (-/+ 50 kg), taken twice daily until disease progression or unacceptable toxicity. Consult the Retevmo Product Monograph for more information.
About RET-Driven Cancers
Genomic alterations in the RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2 per cent of NSCLC; and 10-20 per cent of papillary, Hurthle cell, anaplastic, and poorly differentiated thyroid cancers. Activating RET point mutations account for approximately 60per cent of sporadic MTC and approximately 90 per cent of germline MTC. RET fusion-positive cancers and RET-mutant MTC are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as "oncogene addiction," renders such tumors highly susceptible to small molecule inhibitors targeting RET. RET-driver alterations are predominantly mutually exclusive from other oncogenic drivers.
About LIBRETTO-001
The LIBRETTO-001 Phase 1/2 trial was the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor. The trial included a dose escalation phase (Phase 1) and a dose expansion phase (Phase 2). The Phase 2 portion of the trial had major efficacy outcomes of ORR and DoR, and prespecified secondary endpoints of CNS ORR and CNS DoR, as determined by an independent review committee according to Response Evaluation Criteria in Solid Tumors (RECISTv1.1). Results from the NSCLC population were last presented at the 2019 IASLC World Congress on Lung Cancer (WCLC), while results from the thyroid populations were last presented at the European Society for Medical Oncology (ESMO) 2019 Congress.
About Loxo Oncology at Lilly
Loxo Oncology at Lilly was created in December 2019, combining the Lilly Research Laboratories oncology organization and Loxo Oncology, which was acquired by Lilly in early 2019. Loxo Oncology at Lilly brings together the focus and spirit of a biotech with the scale and resources of large pharma, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new oncology medicines that unequivocally work early in clinical development and will matter to patients.
About Lilly Oncology
For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world.
About Lilly Canada
Eli Lilly and Company is a global healthcare leader that unites caring with discovery to make life better for people around the world. We were founded more than a century ago by Colonel Eli Lilly, who was committed to creating high quality medicines that meet people's needs, and today we remain true to that mission in all our work. Lilly employees work to discover and bring life-changing medicines to people who need them, improve the understanding and management of disease, and contribute to our communities through philanthropy and volunteerism.
Eli Lilly Canada was established in 1938, the result of a research collaboration with scientists at the University of Toronto which eventually produced the world's first commercially available insulin. Our work focuses on oncology, diabetes, autoimmunity, neurodegeneration, and pain. To learn more about Lilly Canada, please visit us at www.lilly.ca.
For our perspective on issues in healthcare and innovation, follow us on twitter @LillyPadCA.
Lilly Forward-Looking Statement
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Retevmo (selpercatinib) for the treatment of metastatic RET fusion-positive NSCLC, advanced or metastatic RET mutation-positive MTC, and advanced or metastatic RET fusion-positive thyroid cancer, and reflects Lilly's current belief. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date or that Retevmo will be commercially successful or receive additional regulatory conditional marketing authorizations. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after this release.
References
1 Retevmo Product Monograph, 2021.
SOURCE Eli Lilly Canada Inc.
Samira Rehman, [email protected], 647-617-1994
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