Merck HIV combo sees approval chances soar to 99%: regulatory roundup
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Regulatory roundup: Merck’s Phase III success propels HIV combo approval chances to 99%

By Reynald Castaneda 08 Nov 2021 (Last Updated November 8th, 2021 11:51)

AbbVie in Parkinson’s disease and Calithera’s glutaminase inhibitor are among other assets reviewed by GlobalData’s Investigative News team.

Regulatory roundup: Merck’s Phase III success propels HIV combo approval chances to 99%
Merck’s positive topline data with its Pifeltro (doravarine) and islatravir combination led their LoA to jump to 99% in HIV. Credit: Merck

Need to know:

GlobalData’s Investigative News team reviews data generated by an in-house model that combines machine learning and its proprietary algorithm. Likelihood of Approval (LoA) provides the probability of a drug in securing market authorization; Phase Transition Success Rate (PTSR) indicates the probability of a drug advancing to the next stage of development. The model uses data points from individual drugs, clinical trials, regulatory milestones, company, and financial databases.

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Merck has likely HIV combo approval win

Merck HIV combo Pifeltro (doravarine) and islatravir combination has reported positive trial results, leading its LoA to jump to 99%. The combo’s LoA jumped by 15 points on 28 October after positive data from two Phase III trials were reported. The two studies involved HIV-infected individuals who are virologically suppressed on other treatments.

The two Phase III trials (NCT04223778, NCT04223791) met the primary efficacy endpoint of percentage of participants with HIV-1 RNA levels ≥50 copies/mL, as per a 25 October company announcement. The results indicated that the Pifeltro/islatravir combo’s efficacy is comparable to other antiretroviral regimens or Gilead Sciences’ Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide).

Pifeltro is a non-nucleoside reverse transcriptase inhibitor (NNRTI), while islatravir is an investigational reverse transcriptase inhibitor. Pifeltro is already approved in HIV in individuals with no prior antiretroviral treatment history and in combination with other antiretroviral agents.

AbbVie reports positive Parkinson’s disease data

AbbVie’s ABBV-951 saw its LoA jump five points to 45% in Parkinson’s disease after the company announced positive topline Phase III data. The company reported results on 28 October and the LoA change took effect on 1 November.

The 174-patient Phase III study (NCT04380142) pit continuous subcutaneous infusion of ABBV-951 against standard of care Merck’s Sinemet (carbidopa/levodopa) tablets. Patients receiving ABBV-951 had a statistically significant increase in the primary endpoint of hours of “on” time without troublesome dyskinesia. Adverse events (AEs) occurred in 8% of the ABBV-951 group and 6% of the Sinemet group, with the most common treatment group AE being infusion-related.

AbbVie has said data from the head-to-head trial will be presented in a future medical conference or journal. ABBV-951, which also features carbidopa and levodopa, is intended to improve motor fluctuations in patients with Parkinson’s disease.

Calithera completes cancer basket trial

Calithera Biosciences’ glutaminase inhibitor telaglenastat hydrochloride (CB-839) saw its PTSR rise following the completion a Phase Ib/II oncology trial. The PTSR grew by seven points to 11% in solid tumours, and by nine points to 38% in pancreatic ductal adenocarcinoma (PDAC).

The 53-subject study (NCT03965845) had its status changed to “completed” as per a 29 October update on ClinicalTrials.gov. GlobalData updated telaglenastat’s PTSR on 2 November. The trial completion also saw a change in telaglenastat’s LoA in solid tumours, growing by one point to 2%. The LoA remained at 1% in PDAC.

The open-label Phase Ib/II sought to investigate telaglenastat in combination with Pfizer’s Ibrance (palbociclib). Telaglenastat inhibits tumour metabolism by blocking the conversion of glutamine into glutamate. Ibrance inhibits cyclin-dependent kinases CDK4 and CDK6.

The trial’s primary endpoint looked for safety signals and maximum tolerated dose on a 28-day timeframe. Maximum plasma concentration and antitumour activity are secondary efficacy endpoints.

Sanofi, Denali likely to progress in MS

Sanofi and Denali Therapeutics’ DNL788 for multiple sclerosis (MS) saw its PTSR leap seven points to 57% after its Phase I trial completed. DNL788 is a receptor-interacting serine/threonine kinase 1 (RIPK1) inhibitor.

The Phase I trial (NCT04982991) assessed the pharmacokinetics of ascending doses of DNL-788, also known as SAR443820, in 14 healthy adults. ClinicalTrials.gov updated the trial from “recruiting” to “completed” on 1 November, and the PTSR change took effect on 3 November.

The completed Phase I also led to a modest increase in the drug’s LoA in MS, which rose by one point to 8%. Sanofi paid Denali USD 125m upfront for a licensing deal that included DNL788. DNL788 is also in development for amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease.

Krystal approval shot bolstered by trial completion

Krystal Biotech’s topical gene therapy beremagene geperpavec (B-VEC) had its LoA rise in epidermolysis bullosa (EB) by seven points to 72%. The LoA update was due to the last dystrophic EB patient in a 31-patient Phase III trial completing the 26-week dosing period and the 30-day safety follow up visit.

The LoA was updated on 27 October, the day after Krystal made the announcement (26 October). Of the 31 patients in the Phase III GEM-3 trial (NCT04491604), 29 participants completed the study with no missing visits, including the three primary endpoint assessment visits, a company media release shows. GEM-3’s primary endpoint is complete wound healing determined by the investigator at week 22 and 24, or week 24 and 26.

Topline data from the placebo-controlled GEM-3 is expected this quarter. Dystrophic EB patients lack functional type VII collagen protein in the skin, leading the skin to tear or blister upon minor contact.

Cortexyme reports negative Alzheimer’s disease data

Cortexyme’s atuzaginstat saw its LoA drop eight points to 17% in Alzheimer’s disease (AD) after a Phase II/III trial missed its coprimary endpoints. Atuzaginstat is an oral small molecule that targets gingipain proteases in the bacterium Porphyromonas gingivalis.

The company announced topline Phase II/III GAIN trial (NCT03823404) results on 26 October, and the LoA change took effect on 28 October. The 643-patient GAIN trial missed its coprimary endpoints Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) and the Alzheimer’s Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL). Both primary endpoints measured change from baseline after 48 weeks.

Cortexyme plans to present additional results at the Clinical Trials on Alzheimer’s Disease (CTAD) conference in Boston, Massachusetts on 11 November. The company has said in a press release it will engage with regulators and stakeholders to determine next steps with atuzaginstat’s development.

MegaPro likely approval in anemia drops

MegaPro Biomedical’s iron deficiency anemia asset MPB-1514 saw LoA dive after the termination of its Phase II study. The LoA dropped by 16 points to 14%. The 49-subject study (NCT03485053) was terminated as per a 28 October update on ClinicalTrials.gov. GlobalData had its latest update on 29 October.

The study evaluated the efficacy and safety of MPB-1514 injections for the treatment of participants suffering from iron deficiency anemia. The trial sought to determine the maximum tolerated dose of MPB-1514. The asset had intended to be used in high doses to increase the number of red blood cells with fewer treatments.

The open-label trial investigated the mean difference in hemoglobin (Hb) from the baseline on a 28-day timeframe as the primary endpoint, evaluating the changes in Hb levels in participants after the dosing. Following the trial’s termination by its sponsor MegaPro, a further Phase IIb study is expected to be carried out.

Aquestive reports positive anaphylaxis trial data

Aquestive Therapeutics’ sublingual film epinephrine AQST-109 improved its chances for further investigations to treat anaphylaxis on the back of positive topline Phase I trial data. AQST-109’s PTSR is now at 81% after a 14-point increase.

Topline Phase I data was revealed on 25 October, with the PTSR updated on 27 October. Data shows AQST-109 has a median time to peak concentration of 15 minutes or less in multiple formulations at 12mg dose and is comparable to autoinjections.

AQST-109 offers a new approach in that it could be an oral alternative to typically injection-administered epinephrine for anaphylaxis. The company expects a crossover trial before the end of the year, and a pharmacokinetic trial in 2022. Following topline data, AQST-109’s LoA also increased by 6 points to 31%.

7 Hills completes solid tumour trial

7 Hills Pharma’s 7HP-349 for solid tumours saw its PTSR jump seven points to 38% after its Phase I trial was completed. The trial completion did not change the drug’s LoA, which remains at 1%.

Houston, Texas-based 7 Hills announced it completed a 60-patient Phase I study (NCT04508179) on 1 November, and the PTSR change took effect 4 November. The primary endpoint was safety and tolerability, and there were no reported treatment-related AE during the single and multiple-ascending dose portions. 7HP349 is an allosteric integrin agonist that can improve antigen-specific immune responses.