Bristol-Myers Squibb’s Opdivo Gets FDA Approval for Esophageal Cancer
The FDA has approved two combination drug regimens based on Bristol-Myers Squibb’s PD-1 inhibitor Opdivo for previously untreated advanced Esophageal Cancer, encroaching on the territory belonging to Merck & Co’s rival Keytruda. The latest approvals are for Opdivo (nivolumab) in combination with chemotherapy or BMS’ CTLA4 inhibitor Yervoy (ipilimumab) as first-line therapy for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (ESCC) that cannot be treated surgically. Both regimens improved overall survival compared to chemotherapy alone in the Phase 3 study, which was reported to be the largest for any immunotherapy in ESCC.
The new approval puts BMS in competition with Keytruda (pembrolizumab) in the first-line advanced ESCC category, as Merck’s medicine has been approved in combination with chemotherapy in both ESCC and GEJ malignancies since March 2021, based on the results of the KEYNOTE-590 trial.
Opdivo may struggle to displace Keytruda because of the broader indication, but having two distinct regimens available for BMS drug may open up a niche in patients with unresectable tumors who are ineligible for chemo.
Aside from the rivalry, the availability of both the Keytruda and Opdivo regimens is a significant step for ward for patients with metastatic ESCC and their doctors, who had few treatment options other than chemotherapy until recently. It has been virtually hard for decades to increase the 12-month overall survival of these patients, but immunotherapies have unlocked some tiny but clinically significant improvements. OS was 13.2 months for Opdivo with chemo versus 10.7 months for chemo alone and 15.4 months versus 9.1 months in patients whose tumors expressed PD-L1 at 1% or above. OS with Opdivo plus Yervoy was 12.8 months, compared to 10.7 months with chemo, and 13.7 months and 9.1 months, respectively, for the PD-L1-positive group. The combination with chemo was associated with an OS of 12.4 months in the Keytruda study, compared to 9.8 months with chemo alone.
Mirati Matches Amgen with Updated Data for KRAS-Inhibitor Adagrasib
Mirati Therapeutics expects to hear from the FDA on its KRAS inhibitor, adagrasib, later this year, seeking to compete with Amgen’s first-to-market competitor, Lumakras. However, new data set to be presented at ASCO indicate that this may be changing. Adagrasib obtained an overall response rate of 43% in a Phase 2 trial of 112 patients with Non-small Cell Lung Cancer (NSCLC) with KRAS G12C mutations who had received at least one prior systemic therapy. Almost the majority of the patients had already received chemotherapy and immunotherapy treatment. A slightly higher top-line result than Amgen obtained in a similar patient cohort treated with Lumakras (sotorasib) in a mid-stage trial indicates that adagrasib can provide at least equivalent efficacy.
However, safety data showed that 43% of patients treated with adagrasib developed significant treatment-related adverse effects, including elevated levels of liver enzymes and anemia. KRAS mutations are observed in around a quarter of NSCLC tumors, with KRAS G12C mutations accounting for about 13% of cases, yet the target has eluded drug developers for decades. Amgen’s first-mover advantage has led to high sales expectations for Lumakras, also known as Lumykras in some territories, with analysts anticipating it will quickly cross the USD 1 billion barriers and become a blockbuster.
However, there is a growing list of competitors, including Novartis (which published Phase 1b results with its JDQ443 candidate earlier this year), Merck & Co, and Boehringer Ingelheim.
FDA Approves Novartis’ Cell Therapy for Follicular Lymphoma in Adults
Novartis proclaimed that the US Food and Drug Administration (FDA) had granted accelerated approval for Kymriah® for the treatment of adult patients suffering from relapsed/refractory (r/r) follicular lymphoma (FL) after two or more lines of systemic therapy. Following the Accelerated Approval Program, continued approval for follicular lymphoma may depend on authentication and description of clinical benefits in the confirmatory trial. Kymriah is now FDA-approved in three indications and remains the only CAR-T cell therapy approved in adult and pediatric settings.
The approval is established on data from the Phase II ELARA trial, in which 90 patients were assessed for efficacy with a median follow-up of around 17 months. 86% of the patients treated with Kymriah achieved a response, including 68% who experienced a complete response.
Prolonged durable response to treatment was shown with an assessed 85% of patients who received a complete response 12 months after initial response. Kymriah was effective in high-risk patients, including heavily pre-treated or had refractory disease, POD24, bulky disease, or those suffering from high Follicular Lymphoma International Prognostic Index (FLIPI) scores.
For 97 patients evaluable for safety at 21 months of median follow-up, the safety profile of Kymriah was remarkable. Fifty-three percent of the patients experienced any-grade cytokine release syndrome, and there were no reported cases of grade III or higher CRS1. Forty-three percent of patients experienced any-grade neurologic events, while 6% of patients experienced higher neurologic events. Eighteen percent of patients were infused in an outpatient setting.
While follicular lymphoma is typically an inert type of cancer, patients with follicular lymphoma may be exposed to a median of 4 lines of treatment, with an upper range of 13 lines. Although various systemic therapies are available, the efficacy of these regimens drops off rapidly in later lines.
“The approval of Kymriah offers patients suffering from relapsed/refractory follicular lymphoma a new treatment option and new hope for improving patient outcomes,” commented Meghan Gutierrez, CEO of Lymphoma Research Foundation. “Having this single infusion cure option helps modify the way healthcare providers approach this type of blood cancer. We compliment those who have contributed to the acceleration of scientific research for the benefit of patients.”
In May 2022, the European Commission (EU) approved Kymriah to treat adult patients with R/R Follicular Lymphoma after two or more lines of systemic therapy, the third indication for which Kymriah is available to patients in the European Union.
NICE Approves Merck’s Keytruda for Adult Patients with Rare Triple-negative Breast Cancer
Today, Merck announced the European Commission approval of Keytruda, Merck’s anti-PD-1 therapy, to be combined with chemotherapy as neoadjuvant treatment and then carried on as monotherapy as adjuvant treatment after surgery for adults having locally advanced/early-stage triple-negative breast cancer at high risk of recurrence.
The approval is formed on results from the pivotal Phase III KEYNOTE-522 trial, in which Keytruda, in combination with chemotherapy before surgery and continued as a single agent after surgery, prolonged event-free survival, reducing the risk of EFS events or death by 37% compared to neoadjuvant chemotherapy alone in this patient population.
KEYNOTE-522 was the first significant, randomized Phase III study to report a statistically remarkable and clinically meaningful EFS outcome among stage II and III triple-negative breast cancer patients. With this decision, the Keytruda combination becomes the first immunotherapy option approved for patients in the European Union in this setting.
The safety of Keytruda plus chemotherapy has been assessed in 3,123 patients across various tumor. Grade 3–5 adverse reactions in patients with triple-negative breast cancer were 80% for Keytruda plus chemotherapy and 77% for chemotherapy.
This approval allows the marketing of this Keytruda regimen in all 27 European Union member states in addition to Norway, Iceland, Northern Ireland, and Lichtenstein. This is the second indication for Keytruda in breast cancer in Europe. In October 2021, KEYTRUDA, along with chemotherapy, was approved for the first-line treatment of certain patients with locally recurrent unresectable or metastatic TNBC.
Merck is committed to delivering advances in gynecologic and breast cancers to patients worldwide through its substantial clinical development program across its oncology portfolio of investigational and approved medicines. Keytruda has been approved in Europe for five new indications across breast cancers, cervical and endometrial cancers as monotherapy, and in novel combinations within just the last year.
Arena Pharmaceuticals’ Etrasimod Aces in Phase 3 Trials of Ulcerative Colitis
Earlier this year, Pfizer acquired Arena Pharmaceuticals hoping that its two lead Phase 3 clinical trials will show positive results. And the same happened for this USD 6.7 Billion acquisition. The pharma giant reported that Arena Pharmaceuticals drug candidate, Etrasimod, for Ulcerative Colitis treatment showed positive outcomes. Treatment with Etrasimod in the clinical trial named ELEVATE UC 12 was associated with a 25% clinical remission rate after 12 weeks compared to a 15% for a matched placebo group. On the other hand, the second hand longer-term clinical trial study, i.e., ELEVATE UC 52, demonstrated that remission was observed in 27% of etrasimod patients and 7% of the placebo group at the 12-week timepoint then was 32% and 7%, respectively after a year. Pfizer announced that the remission data was accompanied by significant improvements in endoscopic measures of disease activity, symptomatic remission, and mucosal healing.
The drugmaker plans to file for the FDA approval later this year for Ulcerative Colitis treatment. The company’s S1P receptor modulator is assessed to be a strong challenge against the rival drug from Bristol-Myers Squibb – Zeposia (ozanimod). The latter drug received FDA approval last year only for both Ulcerative Colitis and Multiple Sclerosis treatment.
Etrasimod will be studied for several other indications as well, such as Crohn’s disease, Alopecia Areata, Eosinophilic Esophagitis, and Atopic Dermatitis, which, if showed positive outcome, might increase the drug’s potential many folds.
FDA Approves Dermavant’s Vtama for Psoriasis
FDA gave a green signal to Dermavant Sciences’ Vtama (tapinarof) for Plaque Psoriasis treatment in adults. This 1% topical cream is the first and only FDA-approved steroid-free topical application of its class. During the Phase 3 evaluation, Vtama cream met all primary and secondary endpoints and showed a statistically significant improvement. Patients who were seen to have clear skin after three months of using the cream also had clear or almost clear skin after four months after stopping the treatment. The safety and tolerability levels remained consistent throughout the three clinical trials (PSOARING 1, 2, and the Phase 3 long-term extension (LTE) study), with most of the adverse events being localized and described as ‘mild to moderate.’
Todd Zavodnick, CEO of Dermavant, said: “We are delighted with our FDA-approved label for Vtama cream, which is for adults with psoriasis, regardless of disease severity, and with an unlimited duration of use.”
The patients who underwent the clinical trial were asked to fill out a questionnaire, and the evaluation of responses was done after the Phase 3 study was completed. The survey indicated a high level of satisfaction in the patients with the treatment from Vtama cream. Almost 85% of the patients surveyed from the Phase 3 LTE study said that Psoriasis management could be done easily by them through the Vtama cream. In addition to that, they also said that they found Vtama to be more effective than previously used topical treatments, with maximum patients agreeing that the cream had a fast rate of absorption, felt nice on the skin, and was not greasy at all.
Vtama has been FDA approved for Mild, Moderate, and Severe Psoriasis and has an unlimited duration of use. Dermavant is ready to launch the topical medication in June 2022.
Johnson & Johnson and Legend Biotech’s CAR-T Carvykti Gets EU Approval for Myeloma
European Commission (EC) has granted conditional marketing authorization to Janssen’s CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) for the treatment of adults with relapsed and refractory multiple myeloma (RRMM). The therapy is approved for patients who have received at least three prior therapies, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 antibody, and have confirmed disease advancement on the last therapy.
Cilta-cel is a chimeric antigen receptor T-cell (CAR-T) therapy featuring two B-cell maturation antigens (BCMA)-targeting single domain antibodies. Janssen had an exclusive worldwide license and collaboration agreement with Legend Biotech USA to develop and commercialize Cilta-cel.
Legend Biotech and Janssen have been working on Carvykti since December 2017 for the treatment of multiple myeloma. Earlier in February 2022, the US FDA approved CARVYKTI™ (ciltacabtagene autoleucel), for the treatment of patients with relapsed or refractory Multiple Myeloma.
In Europe, nearly 51,000+ people were diagnosed with Multiple Myeloma in 2020, and about 32,000+ patients lost their lives. As per the DelveInsight assessment, Multiple Myeloma is slightly more common in males than females. Leading pharma companies, such as Allogene Therapeutics, Poseida Therapeutics, and Precision BioSciences, are actively working to develop CAR-T Cell Therapy for Multiple Myeloma. Currently, several preclinical phase trials are also ongoing. The approval and the launch of the emerging therapies are expected to immensely transform the Multiple Myeloma treatment dynamics in the coming years.
Roche to Present New Data for Glofitamab in Lymphoma at ASCO 2022
Roche has announced that it will present key data on its investigational CD20xCD3 T-cell engaging bispecific antibody, glofitamab, for the first time at the American Society of Clinical Oncology (ASCO 2022) annual meeting and European Hematology Association (EHA 2022).
Data from the phase II NP30179 expansion study demonstrated that, after a median follow-up of more than 12 months, fixed-duration glofitamab (given for a fixed amount of time and not taken until disease progression) induces durable complete responses (CRs) in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who had received a median of three prior therapies.
Glofitamab had a lasting influence 12 months later in patients with relapsed or refractory (R/R) DLBCL who had tried about three other treatments. It is part of Roche’s broad bispecific antibody development program, which may offer a new immunotherapy-based approach to tackle a range of blood cancers. DLBCL cases most commonly affect middle-aged and older adults, and in comparison, they are relatively less common in children and young adults. As per DelveInsight estimate, there were about 72,100+incident cases of DLBCL in the 7MM in 2021, and the cases are expected to increase in the coming years.