Merck’s Sotatercept Clears Phase III Trial

Merck’s USD 11.5 billion acquisition of Acceleron last year was based on the promise of pulmonary arterial hypertension (PAH) candidate sotatercept, which has recently met the mark in a much-anticipated phase III trial. The STELLAR trial found that adding the activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein to stable background therapy resulted in a significant increase in exercise capacity measured using the six-minute walking test in PAH patients, meeting the trial’s primary objectives.

Furthermore, the drug met 8 of 9 secondary endpoints in the study, except for one that looked at the emotional and cognitive impact of PAH on patients, in what appears to be a resounding win for the program.

“In the Phase III STELLAR study, sotatercept added to currently approved background therapy showed a profound effect on the primary efficacy outcome measure of improvement from baseline to 24 weeks in six-minute walk distance. The results from the secondary efficacy outcomes, including a favorable benefit seen in patients’ time to a clinical-worsening event, are especially noteworthy,” said Dr. Dean Y. Li, president of Merck Research Laboratories. “We believe that in totality, the results observed in the STELLAR study suggest that sotatercept has the potential to transform the treatment of patients with PAH. We are moving with urgency on our regulatory applications to bring this investigational therapy to these patients.”

Merck expects sotatercept to generate multibillion-dollar sales, putting it at the center of a renewed push into cardiovascular disease therapies. Merck is counting on Sotatercept to help it reduce its reliance on the USD 17 billion-a-year cancer immunotherapy blockbuster Keytruda (pembrolizumab), which accounts for more than a third of its total sales.

PARP Rivals Closing in On AstraZeneca and Merck’s Lynparza

Since a few years ago, Lynparza from AstraZeneca and Merck & Co. has been the undisputed market leader in the PARP inhibitor category. However, potential rivals are still eroding its market share. Two readouts for competitors from Clovis Oncology and Pfizer this week in prostate cancer—one of several indications on the label for Lynparza (olaparib)—could spark a legal challenge to the USD 3 billion blockbuster drug.

Pfizer reported that the anti-androgen therapy Xtandi (enzalutamide), developed in collaboration with Astellas, and the PARP drug Talzenna (talazoparib), in its phase III TALAPRO 2 trial, decreased radiographic progression-free survival (rPFS) in men with metastatic castration-resistant prostate cancer (mCRPC) who have not received chemotherapy and whose condition is no longer responding to hormonal treatments.

The combination decreased rPFS by 20% when compared to Xtandi plus placebo, and there was a trend toward improved overall survival, which the researchers hope will statistically differ with a longer follow-up. 

After Xtandi or Pfizer’s Zytiga (abiraterone) for mCRPC, AstraZeneca and Merck’s medication was also approved in 2020, but only as a monotherapy for patients with tumors that express homologous recombination repair (HRR) gene mutations, such as BRCA1/2 and ATM. Talzenna may become a treatment option for patients with or without HRR mutations if Pfizer successfully obtains FDA approval for TALAPRO 2, expanding the patient population for whom Lynparza is not currently indicated.

Meanwhile, Clovis reported that its PARP medication Rubraca (rucaparib), which had previously been used to treat men with metastatic castration-resistant prostate cancer (mCRPC) and taxane-based chemotherapy, had improved rPFS in phase III TRITON3 trial.

TRITON3 will serve as the foundation for a new marketing application for the PARP inhibitor in mCRPC patients in an effort to broaden its uses. However, TRITON3’s benefit was almost entirely restricted to the BRCA-positive population, with little effect on ATM, and Clovis has stated that it will now need to talk with the FDA about the final label.

The new data was released not long after AstraZeneca and Merck decided to withdraw an FDA-accelerated approval for a late-line BRCA-mutated ovarian cancer treatment because it did not prove effective in a confirmatory study. If approved, the partners’ request to use Lynparza in the first-line setting for mCRPC, regardless of tumor mutations, will solidify the drug’s advantage over competitors.

FDA Awards Fast Track Designation to Eftilagimod Alpha Plus Pembrolizumab in Frontline NSCLC

The FDA has granted a fast-track designation to eftilagimod alpha for use in combination with pembrolizumab as a frontline treatment for patients suffering with stage IIIB/IV non–small cell lung cancer.

The designation was based on data from the phase II TACTI-002 trial that demonstrated the combination of efti and pembrolizumab obtained an overall response rate of 38.6% by local read in the intent-to-treat population.

Efti is a first-in-class antigen-presenting cell activator for cancer treatment. Efti uses the unique features of LAG-3 to activate innate and adaptive immunity through binding to APCs such as monocytes, dendritic cells, and macrophages via MHC II molecules. Antigens are presented to the adaptive immune system by activating APCs, anti-tumor cells expand, and CD4+ and CD8+ T-cells are amplified.

The TACTI-002 trial assessed efti plus pembrolizumab as a first- or second-line treatment for patients with NSCLC and HNSCC.

Patients in the first-line NSCLC cohort were required to have a histologically/cytologically confirmed diagnosis of stage IIIB non-small cell lung cancer not amenable to curative treatment or stage IV NSCLC not amenable to EGFR/ALK-based therapy. 

Key exclusion criteria for the first-line non-small cell lung cancer cohort included the ability for patients to receive curative intent treatment with either surgical-resection, chemo-radiation, and radiation; prior systemic therapy for stage IV disease unless the completion of treatment with chemotherapy and radiation as part of neoadjuvant/adjuvant therapy occurred at least six months before the diagnosis of metastatic disease; the presence of an EGFR-sensitizing mutation or EML4/ALK gene fusions; or the prior lung radiation therapy of more than 30 Gy within six months of the first dose of trial treatment.

Enrolled patients received around 30 mg of efti every two weeks for the first eight cycles, then every three weeks starting in cycle 9, plus 200 mg of pembrolizumab every three weeks. Each process lasted three weeks.

The primary endpoint of the trial was overall response rate. Secondary endpoints consisted of time to response, duration of response, disease control rate, progression-free survival, overall survival, and safety.

Additional data showed that patients with a PD-L1 TPS of less than one experienced an overall response rate of 28.1%. Those with a PD-L1 TPS between 1% and 49% achieved an overall response rate of 41.7%. Patients with a PD-L1 TPS of at least 1% experienced an overall response rate of 45.5%, and those with a PD-L1 TPS of at least 50% had an overall response rate of 52.6%. Among all patients, the overall response rates for patients with squamous and non-squamous diseases were 35% and 38.9%, respectively.

Further, 8.6% of confirmed responders experienced disease progression within six months, and the median DOR has not yet been reached. The interim median PFS was around 7 months in the ITT, PD-L1 all-comers population. The temporary median PFS was 8.4 months and 11.8 months for patients with a PD-L1 TPS of at least 1% and patients with a PD-L1 TPS of at least 50%, respectively.

Solid Biosciences Announces Acquisition of AavantiBio and Concurrent USD 75 Million Private Placement

Solid Biosciences and AavantiBio declared that the companies have entered into a conclusive merger agreement wherein Solid will acquire AavantiBio, including its pipeline assets and net cash. The companies will focus on advancing a portfolio of neuro-muscular and cardiac programs led by SGT-003 for the treatment of Duchenne. Additional pipeline programs include AVB-202 for the treatment of Friedreich’s ataxia, AVB-401 for BAG3-mediated dilated cardiomyopathy and additional assets for the treatment of unrevealed cardiac diseases. 

Solid announced that it has signed a securities purchase agreement for a $75 million private placement with a limited group of accredited investors and institutional investors in support of the acquisition. The transaction is anticipated to close concurrently with the closing of the merger. The private placement is being led by existing investors such as Perceptive Advisors, Bain Capital Life Sciences, and RA Capital Management, and other new and existing investors are participating in the private placement, including Invus, CaaS Capital Management, Pura Vida Investments, and Laurion Capital Management.

The combined company’s total cash and investments are anticipated to be roughly $215 million as soon as the merger and financing are completed. Solid anticipates that this will be enough to cover the combined company’s expected operating costs and capital expenditure needs by 2025 as well as enable the potential achievement of significant lead programs milestones. Subject to the usual closing requirements, the merger and private placement are anticipated to close in the fourth quarter of 2022.

FDA Clears GlaxoSmithKline’s Boostrix (Tdap) Vaccine for Pertussis 

On 10th October 2022, GSK plc (LSE/NYSE: GSK) announced that the US FDA had approved its pertussis (whooping cough) therapy, BOOSTRIX (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed; Tdap). The therapy is intended for immunization during the third trimester of pregnancy to prevent pertussis in infants younger than two months of age. BOOSTRIX has already been approved in over 80 countries worldwide for treatment against different indications such as tetanus, diphtheria, and pertussis. With the recent approval from FDA, BOOSTRIX now becomes the first vaccine indicated in the US to protect infants younger than two months from pertussis (whooping cough).

As per the statement issued by CDC, “the Tdap vaccination given during pregnancy provides the best protection to infants against whooping cough in the first months of life. Protective antibodies are passed from mother to child when pregnant women are vaccinated.” Moreover, Roger Connor, President – Vaccines and Global Health, GSK, stated that “We’re immensely proud to have the first-ever Tdap vaccine approved by the FDA specifically for this use during pregnancy. We believe this approval may help protect more infants from the potentially life-threatening implications of whooping cough.”

Pertussis, also known as whooping cough, is violent and uncontrollable coughing. As per the CDC, since 2010, about 15,000 to 48,000 pertussis cases are being reported among people of all ages in the United States each year. Pertussis is a bacterial infection, it is being observed that infants are at high risk of complications from whooping cough as compared to other age groups because their immune systems are still developing. Pertussis treatment may be a bit tricky. Along with medication, they may need respiratory support and may require continuous observation. Antibiotics are a suggestive course of treatment. Even though they can take care of the infection, antibiotics cannot treat the cough itself. As per DelveInsight’s assessment, globally, about 10+ key companies are actively working in the Pertussis treatment market. The launch of emerging therapies, including BOOSTRIX, is expected to improve the Pertussis treatment outcome immensely. 

FDA Fast Track Designation to Nanoscope Therapeutics’s MCO-010

On October 10, 2022, Nanoscope Therapeutics announced that the U.S. Food and Drug Administration (FDA) had granted Fast Track Designation (FTD) to its Retinitis Pigmentosa (RP) therapy, MCO-010. Nanoscope’s MCO-010 is an ambient-light activatable Multi-Characteristic Opsin (MCO) optogenetic monotherapy to restore vision in blind patients with Retinitis Pigmentosa via intravitreal injection.

Sulagna Bhattacharya, CEO of Nanoscope, said, “the FDA’s decision to grant FTD underscores the importance of MCO-010 to address a serious unmet need and validates its potential as an effective therapy for patients with Retinitis Pigmentosa. The inputs from Nanoscope Therapeutics future state that they are looking forward to collaboratively interacting with the FDA to assess the next steps in the clinical development and future regulatory review of MCO-010.

Earlier, In January 2022, 27 Retinitis Pigmentosa patients with advanced vision loss were enrolled in a multicenter, randomized, double-masked, sham-controlled RESTORE clinical trial (NCT04945772) of MCO-010. Further, top-line data from the clinical trial are expected in H1 2023. Further, in September of this year, enrollment was completed in Phase 2 open-label STARLIGHT clinical trial (NCT05417126) of MCO-010 in patients with advanced vision loss due to Stargardt disease. Six-month data from the clinical trial are expected in H1 2023.

As per DelveInsight, in 2021, the Retinitis Pigmentosa diagnosed prevalent population in 7MM was observed to be 259,003. The diagnosed prevalence of RP in the United States was found to be 111,994. Moreover, among the European 5 countries, Germany had the highest diagnosed prevalent population, followed by France and the United Kingdom in 2021. There is no known cure for Retinitis Pigmentosa. However, some treatment options are available in the market that can slow down the progression of Retinitis Pigmentosa. Owing to the ongoing therapeutics development activities and the approval and launch of emerging therapies such as MCO-010, among others, is expected to improve the Retinitis Pigmentosa treatment outlook in the coming immensely.