FDA Approves BeiGene’s Brukinsa for CLL/SLL
BeiGene’s Brukinsa (zanubrutinib) for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) has been approved by the US Food and Drug Administration. CLL is a common type of leukemia, accounting for approximately 25% of all new cases each year. SLL is a much rarer form of cancer than CLL, but the malignant cells are concentrated in the lymph nodes rather than the blood and bone marrow.
In the SEQUOIA trial, 479 patients were randomly assigned to either zanubrutinib until disease progression or unacceptable toxicity or bendamustine plus rituximab (BR) for six cycles. An independent review committee (IRC) determined the primary efficacy outcome measure to be progression-free survival (PFS). The median PFS in the zanubrutinib arm was not reached, but it was 33.7 months in the BR arm. PFS had an estimated median follow-up of 25.0 months.
Zanubrutinib was tested in 110 patients with previously untreated CLL/SLL with 17p depletion in a separate non-randomized SEQUOIA cohort. According to the IRC, the overall response rate (ORR) was 88%, but the median duration of response (DOR) was not reached after a median follow-up of 25.1 months. After defeating its rival in a clinical trial, BeiGene looked increasingly likely to become the leading challenger to AbbVie and Johnson & Johnson’s market-leading BTK inhibitor Imbruvica for cancer in October 2022.
Indeed, in the ALPINE study, 652 patients with relapsed or refractory CLL/SLL were randomly assigned to either zanubrutinib or Imbruvica (ibrutinib). The median number of prior lines of treatment was one (from a range between 1-8). The primary efficacy outcome measures at the time of response analysis were ORR and DOR as determined by an IRC, with the ORR in the zanubrutinib arm being 80% and the ORR in the ibrutinib arm being 73%. However, after a median follow-up of 14.1 months, neither arm reached the median DOR.
Brukinsa was the first BTK inhibitor to be recommended for routine NHS use in England and Wales in September 2022 to treat Waldenström macroglobulinemia (WM), a rare form of non-Hodgkin lymphoma (NHL). For CLL/SLL, the recommended zanubrutinib dosage is 160 mg orally twice daily or 320 mg orally once daily until disease progression or unacceptable toxicity.
FDA Grants Accelerated Approval for Seagen’s TUKYSA
TUKYSA (tucatinib) in combination with trastuzumab has been granted Accelerated Approval by the US Food and Drug Administration (FDA) for people with previously treated RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.
Colorectal cancer is the third leading cause of cancer-related deaths in the United States. Colorectal cancer will be diagnosed in approximately 153K people in the United States this year alone, with an estimated 52,550 deaths by the end of 2023. The disease is also becoming more common in younger adults. In the United States, approximately 22% of cases are diagnosed at an advanced stage.
Seagen’s combination regimen, the first FDA-approved treatment for HER2-positive metastatic colorectal cancer, is approved for use in the second-line treatment setting and beyond. The tumor response rate and durability of response from the phase II MOUNTAINEER clinical trial were used to grant accelerated approval. TUKYSA previously received Breakthrough Therapy Designation and Priority Review from the FDA in the same setting.
The MOUNTAINEER trial found a 38% overall response rate (ORR) per blinded independent central review (BICR) in patients between the ages of 24 and 77 who received TUKYSA in combination with trastuzumab. Complete responses were observed in 3.6% of patients, while partial responses were observed in 35%. The median duration of response (DOR) per BICR was 12.4 months.
Continued approval may be conditional on the verification and description of clinical benefit in confirmatory trials: the FDA’s Accelerated Approval Program allows for approval of a medicine based on a surrogate endpoint that is reasonably likely to predict clinical benefit if the medicine addresses an unmet medical need for a serious condition.
A global, randomized phase III clinical trial (MOUNTAINEER-03) is currently underway, comparing TUKYSA in combination with trastuzumab and mFOLFOX6 to a standard of care to serve as a confirmatory trial and potentially supporting future global regulatory submissions.
NICE Recommends Alnylam’s Amvuttra for Rare Form of Amyloidosis
On 19th January 2023, Alnylam UK Limited, the leading RNA interference (RNAi) therapeutics company announced that England’s National Institute for Health and Care Excellence (NICE) had issued a draft guidance recommending Amvuttra (vutrisiran) be available through the country’s National Health Service (NHS) as an option for treating hereditary transthyretin-related (ATTRv) amyloidosis. Following final guidance, now the ATTRv amyloidosis affected people patients will have the option of vutrisiran, meaning that many may now only need to visit the hospital for treatment every three months, compared to existing therapies that need to be administered every few weeks or more frequently. The guidance is expected to be implemented in Wales in due course.
Vutrisiran is a subcutaneous injection designed to treat hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adult patients with stage 1 or stage 2 polyneuropathy. It is a double-stranded small interfering RNA (siRNA) that targets mutant and wild-type transthyretin (TTR) messenger RNA (mRNA). Vutrisiran is developed for increased potency and high metabolic stability to allow for subcutaneous injection once every three months (quarterly). Vutrisiran inhibits the production of the TTR protein by the liver, leading to a reduction in the level of TTR in the blood. By preventing the formation of this protein in patients, it is possible to slow or stop the course of disease, avoiding further damage to patients’ organs and bodily tissues. Results from the pivotal HELIOS-A Phase 3 study demonstrate that vutrisiran rapidly reduces serum TTR levels, has the potential to reverse neuropathy impairment relative to baseline, and improves other key measures of disease burden relative to external placebo in patients with the polyneuropathy of hATTR amyloidosis.
Following the NICE Recommendation, Philip Davey, Country Manager of Alnylam Pharmaceuticals, UK and Ireland, said: “We are delighted that NICE recognised the potential of vutrisiran and that it will now become one of the first rare disease treatments to become available to patients as a result of this accelerated scheme. Our hope is that it will offer benefits both for patients suffering from this devasting condition, and for healthcare professionals who provide them with vital care. Securing this latest guidance for this new advanced medicine would take this pride one step further, demonstrating our commitment to deliver innovative medicines for patients who need them.”
Hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis, historically also referred to as hATTR amyloidosis) is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene. As per DelveInsight’s assessment, in 2020, the total diagnosed prevalent population of hATTR in the 7MM was approximately 12,000. Moreover, among the EU5 countries, Italy has the highest diagnosed prevalent population of hATTR, with approximately 1,500 cases, followed by France in 2020. On the other hand, the United Kingdom had the lowest prevalent population in 2020. The NICE Recommendation is expected to improve the hATTR amyloidosis treatment scenario for affected patients.
TheracosBio Announces FDA Approval of Brenzavvy™ (bexagliflozin) for Type 2 Diabetes
On January 23, 2023, TheracosBio announced that the U.S. Food and Drug Administration (FDA) had approved Brenzavvy™ (bexagliflozin), an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor. BRENZAVVY is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. BRENZAVVY is not recommended for patients with type 1 diabetes mellitus or for treating diabetic ketoacidosis.
TheracosBio evaluated the safety and efficacy of BRENZAVVY in 23 clinical trials enrolling more than 5,000 adults with type 2 diabetes mellitus, which formed the strong basis for the FDA approval for the therapy. Moreover, in the Phase 3 studies, BRENZAVVY significantly reduced hemoglobin A1c and fasting blood sugar after 24 weeks, either as a monotherapy, in combination with metformin, or as an add-on to standard-of-care treatment consisting of a variety of regimens, including metformin, sulfonylureas, insulin, DPP4 inhibitors, or combinations of these agents.
Albert R. Collinson, Ph.D., President, and CEO of TheracosBio, has said that “FDA approval represents a significant milestone for TheracosBio and provides an important treatment option to patients who suffer from type 2 diabetes. We look forward to bringing BRENZAVVY to market”.
Type 2 diabetes is the most common type of diabetes. It occurs when the blood glucose, also called blood sugar, is too high. As per the CDC, more than 37 million Americans have diabetes (about 1 in 10), and approximately 90-95% of them have type 2 diabetes. Type 2 diabetes most often develops in people over age 45, but more and more children, teens, and young adults are also developing it. The approval and the launch of emerging therapies like Brenzavvy™ (bexagliflozin) hold immense potential to transform the Type 2 diabetes treatment market in the coming years.
Roche’s Tecentriq to be Filed for Early-stage Liver Cancer
Roche today announced that the Phase III IMbrave050 study met its primary endpoint of recurrence-free survival at the prespecified interim analysis. In this trial, Tecentriq and Avastin are evaluated as adjuvant therapies for patients with early-stage hepatocellular carcinoma who are at high risk of the illness recurring after surgery. The Tecentriq combination demonstrated a significant improvement in recurrence-free survival in the intention-to-treat population of hepatocellular carcinoma patients with an increased risk of recurrence following resection with curative intent, compared with active surveillance.
Overall survival data were immature at the interim analysis, and follow-up will continue to the following analysis. Safety for Tecentriq and Avastin was consistent with the known safety profile of each therapeutic agent and with the underlying disease. Results from the IMbrave050 study will be discussed with health authorities, including the U.S. FDA and the European Medicines Agency, and presented at an upcoming medical meeting.
Effective treatments are definitely needed as liver cancer mortality rates and incidence rates both rise globally. Roche is collaborating with the community and leveraging its diagnostic and pharmacological expertise to provide treatments for patients that cater to unmet requirements at every stage of liver cancer. Improving outcomes for those with liver cancer is a priority for Roche, and IMbrave050 is a part of that effort. According to data from the IMbrave150 research, Tecentriq + Avastin was the first therapy in more than ten years to significantly outperform the current standard of care in the treatment of unresectable HCC. The Tecentriq combination swiftly established itself as the standard of care for uHCC and is categorically identified as the preferred front-line therapy in most worldwide clinical guidelines.
Roche has an extensive development program for Tecentriq, including multiple ongoing and planned Phase III studies across different genitourinary, skin, lung, gastrointestinal, breast, gynecological, and head and neck cancers. This includes studies evaluating Tecentriq alone and in combination with other medicines and metastatic, adjuvant, and neoadjuvant settings across various tumor types.
FDA Lifts Hold on Astellas’ Pompe Gene Therapy
Astellas Pharma declared that the U.S. Food and Drug Administration had lifted the clinical hold on January 19 for the FORTIS Phase I/II clinical trial accessing the safety, tolerability, and efficiency of investigational AT845 in adults suffering with late-onset pompe disease.
Ha Tran, Executive Medical Director for Astellas, said, “with that same spirit and attention on patient safety, we look forward to proceed with the FORTIS clinical trial and the further development of AT845 as an essential possible new treatment for individuals living with LOPD. As usual, we are grateful to the patients who took part in the FORTIS clinical trial, and we remain committed to exploring novel medicines for patients with significant unmet medical needs.”
Astellas completes the clinical and regulatory tasks to restart dosing in the FORTIS clinical trial, following the clinical hold lift.
Astellas’ financial projections for the current fiscal year, which ends on March 31, 2023, will not be affected by the clinical hold lift.