Merck reports positive mid-stage data for HIV combo therapy
Merck (MRK) announced mid-stage data from its Phase 2b trial NCT03272347 of HIV combination therapy. The trial seeks to assess the efficacy and safety of islatravir in combination with doravirine in treatment-naïve adults with HIV-1 infection. Islatravir is the company’s investigational oral nucleoside reverse transcriptase translocation inhibitor.
The data from Week 96 showed that the combination maintained virologic suppression. The measurement was done using the number of participants achieving HIV-1 RNA levels <50 copies/mL. The data was in line with the reading collected at Week 48. Dr. Joan Butterton of Merck Research Laboratories said, “We continue to pursue new methods for treating HIV, as shown by our growing body of clinical research, and we look forward to sharing new data from our ongoing, global Phase 3 clinical trials for islatravir with doravirine in the future.”
The supplemental Week 96 data demonstrated low rates of participants meeting the definition of protocol-defined virologic failure in both the arms. None of the participants in either cohorts fulfilled the criteria for resistance testing.
The Phase 2b study is an international, multicenter clinical trial. The patients were randomized in four once-daily oral treatment cohorts of islatravir 0.25 mg, 0.75 mg, or 2.25 mg in combination with doravirine (100 mg) and 3TC (300 mg). At Week 96, the ratio of participants maintaining HIV-1 RNA <50 copies/mL in the 0.25 mg, 0.75mg, and 2.25 mg islatravir groups was reported at 86.2 percent, 90 percent and 67.7 percent. In the combination therapy group, the ratio was at 81.1 percent.
Islatravir groups also reported lower number of drug-related adverse events at Week 96 than the Delstrigo group. Between Week 48 and Week 96, no new drug-related serious adverse events were reported. On the basis of data collated, it has been decided to use 0.75 mg dose of islatravir for further clinical development.
The company had conducted two randomized, double-blind, placebo-controlled Phase 1 clinical trials for evaluating the safety, tolerability, and pharmokinetics of single and multiple oral doses of MK-8507. The trials also studied the drug-drug interaction with midazolam, a CYP3A substrate, in healthy adult participants. In Study 1, the participants were given single doses of MK-8507 or placebo from 2 mg to 400 mg, while in Study 2, the participants were administered single doses of MK-8507 or placebo from 400 mg to 1200 mg and multiple doses of MK-8507 or placebo.
The pharmacokinetics of MK-8507 is conducive to once-weekly administration for treating HIV-1 infection. The antiviral efficacy, pharmacokinetics, safety, and tolerability of single doses of 40 mg, 80 mg, and 600 mg of MK-8507 was tested in a Phase 1b open-label, proof-of-concept study. The trial involved 18 HIV-1 infected, antiretroviral-naïve adult males. Single doses of MK-8507 showed reduction in viral load at seven days, in comparison to other NNRTIs dosed daily for the same time frame.
Analysis: According to a market report, HIV-1 continues to be a challenging health issue globally, with the market expected to reach $15.8 billion by 2025. The disease is not yet curable, and therapies still target suppression of viral replication. Combination therapies target different stages in the virus lifecycle and have to be chosen carefully considering adverse effects and co-infections. The NRTI segment accounts for over 40% of the market share. While Gilead Sciences is the leader in HIV-1 therapeutics, other players include AbbVie (ABBV), Bristol-Myers Squibb (BMY), Boehringer Ingelheim, Cipla, F. Hoffmann-La Roche (RHHBY), GlaxoSmithKline (GSK), Johnson & Johnson (JNJ), Mylan (MYL), Teva (TEVA), and ViiV Healthcare, apart from Merck. The combination course therapies cost between ~$17K and ~$38K per year. The primary of Merck’s trial of islatravir combination therapy in HIV-1 is expected to complete by 2Q-2021, and the study will complete by 1Q-2022.
Investment Thesis: Merck is a blue-chip stock. Despite holding strong in the past, it is currently trading at attractive valuation. With its robust market portfolio and healthy development pipeline, the stock price has decent runway up ahead.
Takeda collaborates with Arrowhead Pharma for liver disease program
Takeda Pharmaceutical Company Limited (TAK) announced its new collaboration with Arrowhead Pharmaceuticals Inc. (ARWR). The collaboration will mainly deal with the development of ARO-AAT for treating alpha-1 antitrypsin-associated liver disease. The drug candidate has the potential to become the first-in-class therapy for reducing the production of mutant alpha-1 antitrypsin protein.
Under this arrangement, Arrowhead stands to receive an upfront payment of $300 million. It is also entitled to potential development, regulatory, and commercial milestones payments of up to $740 million. Asit Parikh of Takeda said, “AAT-associated liver disease is a devastating condition for which there are no approved therapies. With its RNAi-based mechanism of action, ARO-AAT has the potential to treat the underlying cause of AATLD, thereby helping patients avoid the need for liver transplantation and associated co-morbidities.”
Takeda and Arrowhead will work together to co-develop ARO-AAT and later commercialize upon approval by the appropriate regulatory authorities. Both the companies will have 50/50 profit sharing structure for this purpose. Takeda will have an exclusive license to commercialize the therapy and will also lead the global commercialization strategy outside of the United States.
ARO-AAT works by knocking down the hepatic production of the mutant alpha-1 antitrypsin (Z-AAT) protein. This protein is believed to cause progressive liver disease in AATD patients. Controlling the production of this inflammatory protein is expected to cease the growth of liver disease. It is also expected to allow the liver to repair and regenerate.
Takeda Pharmaceutical Company Limited is mainly invested in four disease segments, which are Oncology, Rare Diseases, Neuroscience, and Gastroenterology. The company is also working in Plasma-Derived Therapies and Vaccines segments.
Investment Thesis: the stock made a smart recovery from pandemic lows. The company is also working on a COVID-19 treatment and may provide positive impetus to the stock price.
Xenon Pharmaceuticals receives FDA feedback for XEN496 phase 3 clinical trial
Xenon Pharmaceuticals Inc. (XENE) provided an update for its XEN496 program. The company stated that the FDA has completed its review of the clinical trial protocol, enabling Xenon to initiate the Phase 3 clinical trial in pediatric patients with KCNQ2-DEE before the end of this year. It has also received a positive opinion from the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency for the drug candidate.
The phase 3 clinical trial EPIK is a randomized, double-blind, placebo-controlled, parallel group, multicenter clinical study. It seeks to assess the efficacy, safety, and tolerability of XEN496 administered as adjunctive treatment of KCNQ2-DEE. The trial will enroll approximately 40 pediatric patients aged one month to less than 6 years. The patients will be screened and then entered into a baseline period for assessing the frequency of seizures.
The trial will randomize the participants on a 1:1 basis and will administer either XEN496 or placebo for approximately 15 weeks. The treatment period will be followed by a tapering-off period, which will be succeeded by a 28-day safety monitoring period. Dr. Simon Pimstone, Xenon’s Chief Executive Officer, said, “With feedback from the FDA, pharmacokinetic data supportive of our proprietary pediatric formulation, and considerable progress made in site selection and other preparations, we are excited to move forward with our ‘EPIK’ Phase 3 clinical trial studying XEN496 in pediatric patients with KCNQ2-DEE.”
Xenon is a clinical-stage biopharmaceutical company. It has a robust development pipeline of neurology therapies.
Investment Thesis: the stock is currently trading at appreciable discounts to its previous highs. The company has considerably robust prospects ahead and may be an attractive option for a long-term investment portfolio.
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