Roche/Genentech Set Lower Rozlytrek Price To Catch Up With Bayer’s Vitrakvi
Executive Summary
Entrectinib clinched double approvals in the US for ROS1-positive NSCLC and for tumors with NTRK gene fusions – making it the third tumor-agnostic and second NTRK-fusion approval in the US.
Roche's Genentech Inc. announced US Food and Drug Administration approval on 15 August for Rozlytrek (entrectinib) in two indications, making it the second drug approved in the US for solid tumors with a neurotrophic tyrosine receptor kinase (NTRK) gene fusion regardless of tumor type, behind Bayer AG's Vitrakvi (larotrectinib), which was cleared by the FDA last year.
Rozlytrek gained full approval to treat adults with ROS1-positive, metastatic non-small cell lung cancer (NSCLC) as well as accelerated approval to treat adults and children aged 12 and older with NTRK gene fusions whose tumors do not have a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, or when their cancer has progressed after initial treatment or has no satisfactory alternative therapy.
Genentech set a monthly cost for Rozlytrek of approximately $17,050 for adult patients, but for NTRK gene fusion-positive pediatric patients, the price is based on the dose. The company noted that "Rozlytrek is priced lower than the other approved targeted therapy for the treatment of NTRK fusion-positive solid tumors, and in-line with the other approved targeted therapy for ROS1-positive metastatic NSCLC." Pfizer Inc.'s kinase inhibitor Xalkori (crizotinib) is approved for ALK- and ROS1-positive NSCLC.
Rozlytrek, a selective inhibitor of ROS1 and NTRK, is an important addition to Roche's commercial oncology portfolio at a time when its biggest cancer brands – including Herceptin (trastuzumab), Rituxan (rituximab) and Avastin (bevacizumab) – are beginning to face biosimilar competition in the US. (Also see "Roche’s Pipeline Prospects Promise Steady Sailing To More Growth " - Scrip, 1 Aug, 2019.) Amgen Inc. and Allergan PLC announced the launch of their Avastin and Herceptin biosimilars Mvasi and Kanjinti in July. (Also see "US Market For Therapeutic Cancer Biosimilars Will Be Tested By Mvasi, Kanjinti Launches" - Scrip, 19 Jul, 2019.)
Rozlytrek's first global approval came in Japan in June after an expedited "sakigake" review for the NTRK gene fusion indication, making it the first tumor-agnostic drug approved in that country.
However, hopes for an accelerated assessment in the EU were dashed in March when the European Medicines Agency determined that it could not conduct a rapid review for both the ROS1-positive NSCLC and NTRK gene fusion indications on an expedited basis. SC124846 Vitrakvi is expected to be the first tumor-agnostic therapy approved in the EU. (Also see "Bayer's Vitrakvi On Track To Become EU’s First Tumor-Agnostic Cancer Treatment" - Pink Sheet, 26 Jul, 2019.)
Rozlytrek had been granted a breakthrough therapy designation from the US FDA as well as an orphan drug designation.
It marks the third tumor-agnostic approval in the US, following Vitrakvi and Merck & Co. Inc.'s Keytruda (pembrolizumab). (Also see "FDA Nod For Loxo/Bayer Tissue Agnostic Drug Marks Paradigm Shift In Cancer " - Scrip, 27 Nov, 2018.) Keytruda was cleared by the FDA in 2017 for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors. (Also see "Keytruda Approval Opens New Routes For Immuno-Oncology" - Scrip, 24 May, 2017.)
Data from four Phase I and II clinical trials testing Rozlytrek in several tumor types supported the new drug application (NDA) in the US, including breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, lung, salivary gland, pancreatic, sarcoma and thyroid cancers. The product received accelerated approval based on overall response rates (ORRs) and duration of response (DoR) in those trials, but evidence of clinical benefit must be confirmed to secure full approval.
Genentech reported that Rozlytrek shrank ROS1-positive NSCLC tumors in 78% of the 51 patients evaluated with DoR ranging from 1.8 months to more than 36.8 months in 40 patients. Tumors shrank in more than half of the evaluated patients with NTRK gene fusion-positive solid tumors (ORR=57%; n=54) across the trials, with DoR ranging from 2.8 months to more than 26 months (n=31 out of 54).
Data presented at the European Society of Medical Oncology (ESMO) meeting last fall did not appear as strong as results seen in patients with NTRK gene fusion-positive tumors who were treated with Vitrakvi. However, Genentech believes Rozlytrek's activity in the central nervous system (CNS) may give it an advantage. (Also see "Plenty Of Potential For Roche's Entrectinib Despite Lack Of ESMO Enthusiasm" - Scrip, 24 Oct, 2018.)
That's important for both NTRK gene fusion and ROS1-positive patients, since about 40% of ROS1-positive lung cancer patients have metastases in the CNS, according to Janet Freeman-Daily, co-founder of a patient and caregiver group called The ROS1ders.
The Rozlytrek development program and the regulatory strategy for the drug has included two elements important to the US FDA – the inclusion of pediatric patients in clinical trials and the use of real-world data to support the NDA.
"Traditionally, clinical development of new cancer drugs in pediatric populations is not started until development is well under way in adults, and often not until after approval of an adult indication,” said Richard Pazdur, director of the agency's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, in a statement about the Rozlytrek approval. However, "efficacy [for Rozlytrek] in adolescents was derived from adult data and safety was demonstrated in 30 pediatric patients," Pazdur noted.
Data from 29 patients between the ages of 4.9 months and 20 years treated with Rozlytrek in Genentech's Phase I/Ib STARTRK-NG study were presented during the American Society of Clinical Oncology (ASCO) meeting in June. NTRK and ROS1 are common biomarkers in various pediatric cancers. (Also see "Pediatric Oncology Advances Could Prompt More FDA-Required Studies" - Scrip, 16 May, 2019.)
In support of the drug's lung cancer-specific indication, Roche partnered with its Flatiron Health subsidiary to collect real-world data from ROS1-positive NSCLC patients to use as a comparator for its single-arm study in the Rozlytrek NDA. Roche remains a leader among biopharma firms acting on the FDA's interest in real-world data. (Also see "Real-World Reluctance? Despite Guidance, Drug Developers Wary Of RWE-Based Trials" - Scrip, 12 Jul, 2019.)
Roche is working with Foundation Medicine Inc. on getting its Foundation One CDx cleared to help doctors determine which patients are appropriate for treatment with Rozlytrek, but it has not been submitted yet to the FDA for approval.
"Until the companion diagnostic is approved, ROS1 and NTRK gene fusions can be identified using molecular tests, which can include next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and polymerase chain reaction (PCR)," Genentech noted.
The company will help eligible patients who need assistance paying for Rozlytrek through its Genentech Access Solutions program.
Editor's Note: This article was updated on 16 August to note that Rozlytrek received full approval for ROS1-positive NSCLC and accelerated approval for solid tumors with NTRK gene fusions, not accelerated approval for both.