Amgen Reveals the Top-line Result of its CodeBreak-200 trial of Lumakras in Lung Cancer

The top-line result of Amgen’s CodeBreak-200 trial of Lumakras in lung cancer was presented in abstract form at ESMO two weeks ago, showing a 34% improvement in progression-free survival (PFS) compared to chemotherapy. The full data was presented as a late-breaker later at the ESMO 2022, so it is subject to change, but it currently shows a significant reduction in disease progression or death in patients with KRAS inhibitor in KRAS G12C-mutated NSCLC compared to docetaxel, but no improvement in overall survival.

Amgen points out that the study was not statistically powered to show a difference in survival, although it was a secondary endpoint. So far, there is no indication of whether there was an improvement in OS with Lumakras that could be sustained over time. Nonetheless, CodeBreak-200 will most likely serve as a confirmatory study for Lumakras (sotorasib) approval in this heavily pretreated patient population, which the FDA granted in May 2021.  This is significant because Mirati, like Amgen, is seeking approval for its KRAS inhibitor adagrasib via the accelerated pathway based on the strength of mid-stage data in the same indication. 

If Amgen can secure full approval for Lumakras before the FDA’s 14 December decision date for Mirati’s drug, the company may be forced to wait for its own phase III trial, which is scheduled to read out in August 2023.

KRAS mutations are found in approximately one-quarter of NSCLC tumors, with KRAS G12C mutations accounting for approximately 13% of cases, but 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 markets, with analysts predicting it will easily cross the USD 1 billion mark and become a blockbuster.

FDA Clears Bristol-Myers Squibb’s deucravacitinib for Psoriasis

Deucravacitinib, one of the main pipeline assets in Bristol-Myers Squibb’s USD 74 billion takeover of Celgene in 2019, has been approved in its first market as a treatment for moderate-to-severe plaque psoriasis. The US FDA has approved Sotyktu, a first-in-class tyrosine kinase 2 (Tyk2) inhibitor, and BMS says it will launch the new drug later this month, aiming to compete with Amgen’s USD 2.3 billion oral psoriasis therapy Otezla (apremilast).

BMS previously stated that Sotyktu could be a USD 4 billion seller at its peak, owing to head-to-head studies demonstrating that it was more effective than Amgen’s drug, which acts as a PDE4 inhibitor, in treating moderate-to-severe psoriasis.

According to the POETYK PSO-1 and POETYK PSO-2 results, 59% and 54% of patients treated with Sotyktu achieved 75% skin clearance, compared to 35% and 40% for Otezla. BMS has set a list price of USD 6,164 for a 30-day supply of the new drug, which is approximately 42% more than the USD 4,344 Amgen charges wholesalers for a 30-day supply of Otezla before any discounts or rebates.

It received FDA approval in December for the treatment of adult patients with plaque psoriasis, regardless of the severity of symptoms, making it an option for all of the estimated 8 million people in the United States who have the skin disorder. It had only been approved for moderate to severe cases since 2014. Sales slowed from the beginning of the pandemic until the first quarter of 2022 but began to recover in the second quarter, rising 11% to USD 594 million.

“The approval of Sotyktu represents an exciting day for patients suffering from moderate-to-severe plaque psoriasis who are not satisfied with topical and conventional treatments,” said Samit Hirawat, BMS’ chief medical officer. He further added, “We believe Sotyktu is a breakthrough in the treatment of patients with this condition, and we’re excited about its potential in other immune-mediated diseases.”

Deucravacitinib will not be labeled with any JAK-like warnings, which is a bonus as BMS plans to expand its use into other chronic inflammatory diseases such as inflammatory bowel disease, lupus, and psoriatic arthritis.

European Commission Approves Gilead Sciences’ Tecartus 

European Commission (EC) has approved Kite’s (a Gilead Company) CAR T-cell therapy Tecartus® (brexucabtagene autoleucel) for the treatment of relapsed or refractory (r/r) B-cell precursor Acute Lymphoblastic Leukemia (ALL). The therapy is approved for adult patients 26 years of age and above. After the major decision from the European Commission, the Tecartus became the first and only CAR T-cell therapy for r/r Acute Lymphoblastic Leukemia in Europe.

Tecartus is approved based on data from the phase I/II ZUMA-3 study in adult patients with r/r Acute Lymphoblastic Leukemia. As per the data presented by the Kite, it is observed that 71% of the evaluable patients achieved complete remission (“CR”) or CR with incomplete hematological recovery (CRi) with a median follow-up of 26.8 months.

Over the last few years, the Acute Lymphoblastic Leukemia treatment paradigm has evolved significantly due to the launch of several therapies that have improved treatment scenarios. The first chimeric antigen receptor (CAR) T-cells for r/r pediatric and young adult ALL patients, namely Kymriah, have also been approved by various healthcare regulatory authorities worldwide, thereby improving the treatment outcome.

Acute Lymphoblastic Leukemia is an aggressive type of blood cancer, and approximately 64,000 people are diagnosed with it each year globally. As per the estimates, it is observed that Acute Lymphoblastic Leukemia is more frequent in males compared to females. As per DelveInsight’s assessment, the total incident cases of Acute Lymphoblastic Leukemia in the 7MM were observed to be 10,837 cases in 2020, which are expected to grow in the coming years. Among the European-5 countries, Germany had the highest incident population of Acute Lymphoblastic Leukemia, followed by France, the UK, and Italy. On the other hand, Spain had the lowest number of incident cases in 2020. Presently, Tecartus is approved in the United States and Europe for treating adult patients with relapsed or refractory mantle cell lymphoma (MCL). The European Commission’s approval of Tecartus will significantly improve the relapsed or refractory (r/r) Acute Lymphoblastic Leukemia treatment outcome in the coming years.

Gilead Sciences’ Trodelvy Shows Positive Results in TROPiCs-02 Trial

Gilead Sciences announced Phase 3 TROPiCS-02 study evaluating Trodelvy® (sacituzumab govitecan-hziy) versus comparator chemotherapy (physicians’ choice of chemotherapy, TPC) in patients with HR+/HER2- metastatic breast cancer who received endocrine-based therapies and at least two chemotherapies.

As per the data published by Gilead, Trodelvy demonstrated a statistically significant and clinically meaningful improvement of 3.2 months in OS compared to TPC. OS was a key secondary endpoint of the trial. Moreover, the other key secondary endpoints, including objective response rate (ORR), demonstrated statistically significant improvement in favoring Trodelvy versus TPC.

Gilead Sciences presented the data during the European Society for Medical Oncology (ESMO) Congress 2022 as a late-breaking oral presentation (LBA76) in Paris Expo Porte de Versailles, France. Bill Grossman (MD, Therapeutic Area Head, Gilead Oncology) stated that “with these data from TROPiCS-02, Trodelvy has now demonstrated a survival benefit in both pre-treated HR+/HER2- metastatic breast cancer and second-line metastatic TNBC – two difficult-to-treat forms of breast cancer,”.

HR-positive/HER2-negative breast cancer is the most common form of breast cancer and also accounts for a higher percentage of all breast cancers. As per DelveInsight, the total incident population of breast cancer in the 7MM was estimated to be 631,014 in 2018. Among the 7MM, the highest prevalent breast cancer cases were registered in the United States. Among the EU5 countries, Germany accounted for the maximum number of incident cases, followed by Italy, France, and the UK. While Spain accounted for the least cases.

HR-positive cancer is usually treated with hormone therapies or a combination of hormone therapies with targeted therapy to help stop tumor growth. The advanced stage positive results by Gilead Sciences’ Trodelvy raise the hope for better treatment outcomes for patients with HR-positive/HER2-negative breast cancer.

Evidence Builds for BioNTech’s Amplified CAR-T Therapy

BioNTech gained the limelight due to its amplified CAR-T therapy. BioNTech has been known for its wonders in the mRNA-bassed vaccines and COVID-19 shots partnered with Pfizer in the past. 

Its nascent BNT-211 candidate comprising CAR-T targeting antigen Claudin-6 on cancer cells has shown results after its phase-I and phase-II trials. The candidate will be coupled with an mRNA vaccine responsible for amplifying CAR-T’s activity. 

The vaccine shows action by stimulating Claudin-6, responsible for presenting foreign particles (antigens) to the T-cell. As soon as the T-cell recognizes the antigen, it generates an immune response to kill the antigen. Solid tumors have shown resistance against to majority of targeted cell therapy, and CAR-Ts have led to potentially overcoming this drawback. 

As per the new data, almost 22 patients suffering from solid tumors were given CAR-T therapy, 13 patients with testicular cancer, and four from ovarian cancer. The study’s results obtained through the survey showed a 33% overall response rate and a controlled rate of 67%. Moreover, BNT-211 was recently awarded Priority Medicines (PRIME) status by the EMA. This could eventually lead to perks during the regulatory review in the future. 

“This new dataset further supports the encouraging results we have seen for BNT211 to date,” commented Prof Özlem Türeci, BioNTech’s chief medical officer.

“Together with the recently granted PRIME designation for BNT211 in testicular cancer it also reinforces our strategy to combine two of our key technology platforms in hard-to-treat tumour indications,” she added.

TIL Therapy Improves on Yervoy in Melanoma Trial

During a melanoma trial, tumor-infiltrating lymphocyte (TIL) therapy shows a 50% reduction in the risk of progression or death compared to the pre-existing drug ipilimumab (Yervoy) for patients suffering from treatment-refractory melanoma. 

“This is the first multicenter, randomized, controlled trial studying a T-cell therapy in solid cancer, in this case comparing TIL to ipilimumab as more or less a second-line treatment for metastatic melanoma. TIL significantly improved PFS,” lead investigator John Haanen, MD, Ph.D., Netherlands Cancer Institute in Amsterdam, said in a press conference at the meeting.

Tumor-infiltrating lymphocyte (TIL) therapy is the first randomized study to show cell therapy improves outcomes in patients with solid cancers. The development of tumor-infiltrating lymphocyte (TIL) therapy raises hopes for improved treatment and potential cure for patients with a wide range of solid metastatic tumors. TILs work by recognizing tumor cells as foreign cells and killing them by penetrating inside them.  

Study reports at the ESMO Congress 2022 showed that patients treated with TIL therapy had significantly longer median progression-free survival of 7.2 months compared to 3.1 months in those receiving ipilimumab. Moreover, exploring the possible mechanism by which TIL therapy is effective in patients who have failed anti-PD-1 treatment, Haanen suggested. 

GSK’s Daprodustat will have to face FDA Advisory Committee 

GSK’s Daprodustat to treat anemia associated with chronic kidney disease (CKD) will have to face the FDA Advisory Committee before the US regulator, which is about to deliver a verdict on the drug in early next year. 

Daprodustat is about to become the first drug in the HIF-PHI inhibitor class to land up in the US market after the other two drugs- FibroGen/AstraZeneca’s roxadustat and Akebia’s vadadustat rejected by US FDA as their safety data submitted wasn’t strong enough to allow approval. 

Although GSK was hoping to escape FDA for daprodustat, now it will have to answer the drug’s safety, and efficacy at the Cardiovascular and Renal Drugs Advisory Committee (CRDAC) set for 26 October. The company has set a peak sales target of £500 million to £1 billion ($575 million to $1.15 billion) for the drug.

Daprodustat has been filed with the FDA on the strength of the ASCEND phase III trials program, which included five trials in CKD patients, including those needing dialysis, and showed that the drug offered an oral alternative to injectable erythropoietin stimulating agents (ESAs) for anemia, without sacrificing efficacy. HIF-PHI drugs generate a red blood cell-generating response whenever ischemia is detected. They work differently from ESAs like epoetin alfa and darbepoetin alfa, which stimulate the production of more blood cells in the bone marrow.

HIF-PH inhibitors could also avoid some side effects linked to ESAs, including a higher risk of blood clots and tumors, and don’t need to be refrigerated during storage.

It was found that the US FDA did not approve the use of roxadustat and asked for another clinical trial to bolster the data for the drug due to a lack of appropriate cardiovascular safety; however, it was approved in the EU. 

FDA Grants Coveted Breakthrough Status to Pfizer’s Vaccine against Group B Streptococcus (GBS) 

FDA has granted Breakthrough Therapy Designation to Phizer’s GBS6 against Group B Streptococcus (GBS). 

The vaccine focuses on preventing invasive GBS disease due to the vaccine serotypes in newborns and young infants by active immunization of their mothers during pregnancy.

The decision was informed during the interim analysis of a placebo-controlled phase III study focused on evaluating the safety and immunogenicity of GBS6 in healthy pregnant women aged 18 to 40 years. The pregnant mothers were vaccinated during the second or early third trimester of pregnancy. 

“GBS infections can have a devastating effect on newborns and their families. While prenatal screening and antibiotics during childbirth help provide protection against GBS in developed countries, this approach is not fully protective in the first week of life; presents multiple challenges in low- and middle-income countries; and has not been shown effective in preventing disease globally in infants beyond the first week of life and through the vulnerable first three months of life,” said Annaliesa Anderson, Ph.D., Senior Vice President and Head of Vaccine Research & Development, Pfizer. “If approved for pregnant women, GBS6 could help protect newborns from the serious illnesses caused by this disease like meningitis, pneumonia, and sepsis – fulfilling a critical global public health need. We are encouraged by today’s decision and look forward to discussing GBS6 with the FDA and other regulatory agencies to potentially reduce neonatal deaths and positively impact the existing global disease burden of GBS.”

The FDA’s Breakthrough Therapy Designation is designed to accelerate the development and review of drugs and vaccines intended to treat or prevent serious conditions.