On Tuesday (April 7), Gov. Andrew Cuomo projected that the state is reaching a plateau in coronavirus hospitalizations due to strict social distancing measures.
“To the extent that we see a flattening or a possible plateau, that’s because of what we’re doing and we have to keep doing it,” Mr. Cuomo said. (WSJ)
Social distancing is working. We took dramatic action. It is flattening the curve.
In 2012, Novartis acquired a specialized facility from the former Dendreon for $43 million. Dendreon went bankrupt trying to establish its once-promising prostate cancer vaccine Provenge.
Dendreon’s Morris Plains, New Jersey, facility is a 173,100 square foot state-of-the-art IMF.
In July 2018, before EU approval, Novartis announced that it had signed an agreement with CellforCure, a French CDMO, to produce CAR-T cell therapies. Manufacturing at Cell for Cure’s site in Les Ulis, a city southwest of Paris, would mimic the processes Novartis has in place at its Morris Plains, New Jersey hub.
In September 2018, Novartis paid $40 million for a 9% stake in Cellular Biomedicine Group (CBMG), a Shanghai-based firm which will manufacture CAR-T cell therapy Kymriah for the China market and license select proprietary technology to Novartis for global use.
In addition to manufacturing areas for novel CAR-T cell therapies, the new building also hosts the production of innovative, difficult-to-manufacture solid dosage forms such as tablets and capsules.
The El Segundo site is estimated to have the capacity to produce up to 5,000 patient therapies per year. The plant’s location, adjacent to Los Angeles International Airport, is intended to expedite receipt and shipment of engineered T-cells from and to patients across the United States and Europe. According to Kite, the time from when a patient’s materials are shipped to the facility to when the engineered T cells are returned to the patient is approximately 14 days.
When Yescarta was approved in Oct 2017, Gilead’s statement said in the ZUMA-1 pivotal trial, Kite demonstrated a 99 percent manufacturing success rate with a median manufacturing turnaround time of 17 days, which is important to patients given the potential for rapid disease progression in this population.”
In 2018, three month before Yescarta is approved in Europe, Kite leased a new facility in the Netherlands to engineer cell therapies in Europe – a 117,000 square-foot site in Hoofddorp (SEGRO Park Amsterdam Airport). The plant is expected to be operational in 2020 and saving 3-4 days in delivery (from Europe to LA). The current time including international delivery, from apheresis to delivery of Yescarta, is 26-29 days.
Meanwhile, in addition to the Netherlands facility, Kite said it had recently purchased a new building in Santa Monica from Astellas Pharma Inc. that will be used for cell therapy research, development and the expansion of clinical manufacturing capabilities, and has leased a 26,000 square-foot facility in Gaithersburg, Maryland.
In July 2018, it also added Michael Amoroso as Senior Vice President and Head of Worldwide Commercial, Cell Therapy. Mr. Amoroso was leading Ensai’s American commercialization of oncology business; but more importantly, he worked at Celgene on several oncology roles before serving as Commercial Lead, Global Marketing for Celgene’s CAR T programs. His current title is CMO of Kite.
Source: fiercepharma, Frederick County Office of Economic Development
On Gilead’s 2019 1st quarter earnings call, its new CEO said they will separate Kite into its own business unit.
In July 2019, Kite announced that Christi L. Shaw will join as CEO of Kite. Ms. Shaw was serving as Senior Vice President of Eli Lilly &. Co., and President of Lilly Bio-Medicines.
Later in July 2019, Kite announced plans for a new 67,000-square-foot facility in Oceanside, California, dedicated to the development and manufacturing of viral vectors, a critical starting material in the production of cell therapies. The facility will go live in the second half of 2021.
With Yescarta’s annual sales of $456 million in 2019 and Kymriah catching up, the acquisition price paid in 2017 by Gilead was indeed very high.
In its 19Q4 earnings, Gilead disclosed an $800 million write-down related to a Kite Pharma setback in indolent non-Hodgkin lymphoma. That followed an $820 million write-down this time last year related to Kite’s multiple myeloma candidate KITE-585. [fiercepharma]
The competition will become more fierce as BMY just submitted application for its CAR-T therapy acquired from Celgene (Celgene acquired from Juno) -lisocabtagene maraleucel (liso-cel). The treatment is also for adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after at least two prior therapies.
BMY’s data: among patients evaluable for efficacy (n=256), the overall response rate (ORR) was 73% (187/256, 95% CI: 67 – 78) with 53% of patients (136/256, 95% CI: 47 – 59) achieving a complete response (CR). Responses were similar across all patient subgroups. Among all patients, 79% (213/269) had grade 3 or higher treatment-emergent adverse events (TEAE). Instances of any grade cytokine release syndrome (CRS) occurred in 42% (113/269) of patients at a median onset of 5 days and grade 3 or higher CRS occurring in 2% (6/269) of patients.
CAR-T therapies have shown superior effects in treating blood cancers. Kymriah’s initial approved indication is B-cell precursor ALL that is refractory or in second or later relapse for patients up to 25 years of age. There are approximately 3,100 patients aged 20 and younger are diagnosed with ALL each year; 15-20 percent of pediatric B cell precursor ALL patients relapse after their initial remission.
On Aug 28, 11 days after Kymriah’s approval, another CAR-T cell therapy company Kite Pharma was acquired by Gilead for $11.9 billion. The $180.00 per share acquisition price represents a 29% premium to Kite’s closing on Friday, August 25, and a 50% premium to the company’s 30-day volume weighted average stock price.
At the time of acquisition, Kite’s lead candidate was under FDA’s priority review and had submitted the first CAR-T therapy application in Europe for the treatment of relapsed/refractory DLBCL, TFL and PMBCL with the European Medicines Agency (EMA).
On Oct 18, FDA approved Kite’s Yescarta for use in adult patients with large B-cell lymphoma after at least two other kinds of treatment failed, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. DLBCL is the most common type of NHL in adults, with 24,000 new cases diagnosed each year in the US (1/3 of newly diagnosed NHL).
Concurrently, in Gilead’s press release, it estimated that in the US each year there are approximately 7,500 patients with refractory DLBCL who are eligible for CAR T therapy.
In August 2018, Yescarta received European Marketing Authorization for adult patients with relapsed or refractory DLBCL and PMBCL, after two or more lines of systemic therapy; Kymriah was approved in EU for the treatment of pediatric and young adult patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse; and for the treatment of adult patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.
lower limit of the 95% confidence interval for ORR is 70.9%, which is above the pre-set null hypothesis rate of 20%
40 subjects (63.5%) had the best response of CR within the first 3 months after infusion
12 subjects (19.0%) had the best response of CRi.
Among the 52 responders, the median duration of response (DOR) was not yet reached (range: 1.2 to 14.1+ months) with the median follow-up of 4.8 months.
84% (n=57) experienced Grade 3 or higher events
Cytokine release syndrome (CRS) occurred in 79% of patients; CRS Grade 3 or higher occurred in 49% of patients
On ASH 2018, Novartis presented an updated ORR rate of 82.3% (n=65/79); relapse-free survival was 62% at 24 months.
r/r DLBCL
Yescarta was approved in 2017 based on an ORR of 72% (n=73/101), with a CR rate of 51%. SAEs Grade 3 or higher occurred in 48 (44%) patients. CRS occurred in 94% of patients; CRS Grade 3 or higher occurred in 13% of patients.
When Kymriah was approved for r/r DLBCL in 2018, the overall response rate (ORR) was 50% at 3 months (n=34/68). On ASH 2019, in the 24-month analysis of the JULIET trial, ORR was 52% (N=115).
Dots to connect: Gilead’s drug Remdesivir for Ebola, Abbvie’s Kaletra (Lopinavir/Ritonavir), Roche’s Tamiflu, Oseltamivir generic versions, JNJ’s Prezista, restaurant/coffee chains Yum China, Luckin Coffee, Starbuck, airline industry, drop in demand for oil and oil prices, other travel related industries such as Trip.com and Huazhu, second-order effects on internet-based services & healthcare services investments, etc.
Genetic testings have different significances and it seems that BRCA is currently the only gene of hard demand (CDx) in cancer treatments among germline testings.
Myriad and AstraZeneca
Back in Dec 2014, AstraZeneca received FDA approval for the first PARP inhibitor LYNPARZA, as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.
Myriad is a pioneer in genetic testing, especially for BRCA. BRACAnalysis CDx is blood-based, using PCR and Sanger sequencing to gauge single nucleotide variants and small indels, and multiplex PCR to assess large deletions and duplications.
Foundation Medicine and Clovis Oncology
In Dec 2016, Foundation Medicine’s FoundationFocus CDxBRCA was approved by FDA as the first NGS-based companion diagnostic, for Clovis Oncology’s PARP inhibitor Rubraca (rucaparib), for patients with deleterious BRCA mutation (germline and/or somatic)-associated advanced ovarian cancer who have been treated with two or more chemotherapies.
Myriad and Clovis
In April 2017, Myriad and Clovis Oncology announced the CDx collaboration on Rubraca. “The companion diagnostic test approved with Rubraca does not discriminate between germline and somatic mutations. Knowledge of germline status is important to provide patients appropriate counseling.”
In Jan 2018, AstraZeneca’s LYNPARZA received approval for expanded usage in breast cancer, for patients with germline breast cancer susceptibility gene (BRCA) mutated, HER2-negative metastatic breast cancer, who have been previously treated with chemotherapy. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior hormonal (endocrine) therapy or be considered inappropriate for endocrine treatment.
FDA also expanded the approval of the BRACAnalysis CDx, an approved companion diagnostic to Lynparza, to include the detection of BRCA mutations in blood samples from patients with breast cancer.
While the market expanded, more players are coming to this field. Since 2013, there is a growing number of labs providing BRCA testings – mostly are not for CDx.
