DewDiligence
1 month ago
MRK’s RSV prophylactic, Clesrovimab meets_all_endpoints_in_phase-2/3_trial:
https://www.businesswire.com/news/home/20240723229019/en
If approved, Clesrovimab will compete against GSK’s Beyfortus.
Beyfortus and Clesrovimab are effective at preventing RSV for one season, but they do not confer lasting immunity. Patients taking these drugs are likely to contract RSV infection in a subsequent season, and hence the need for RSV treatments, such as those being developed by ENTA, is not diminished.
DewDiligence
1 year ago
MRK sues US over IRA drug-price “negotiation”:
https://www.wsj.com/articles/merck-challenges-u-s-governments-new-powers-to-negotiate-drug-prices-127d4b0c Drugmaker Merck & Co. filed a lawsuit on Tuesday challenging the U.S. government’s plan to negotiate drug prices, saying it is unconstitutional.
Drugmakers were expected to file lawsuits challenging the program, especially as Medicare neared the date later this year when it began naming some drugs it would target for price negotiations.
Among the drugs that analysts expected to face price negotiations are Merck’s top-selling product, the cancer immunotherapy Keytruda.
Merck’s complaint takes issue with the negotiation program’s enforcement rules, which include the power to levy an excise tax of up to 95% of a drug’s U.S. sales if a pharmaceutical company refuses to sell the drug to Medicare patients. Merck said the tax would be coercive and violate the constitution’s Fifth Amendment ban on private property being taken for public use without just compensation. [The so-called “takings” clause.]
Merck also said the law would force companies to agree that the government-mandated prices are “fair,” violating its free speech rights under the First Amendment. For biotech investors, there’s a lot riding on the outcome of this lawsuit and related cases.
Want more details? See https://www.cms.gov/files/document/medicare-drug-price-negotiation-program-initial-guidance.pdf (91 pages).
DewDiligence
2 years ago
Keytruda fails again in prostate cancer—one of the few cancer indications where it has not seen a positive outcome:
https://www.businesswire.com/news/home/20230124006084/en/Merck-Announces-KEYNOTE-991-Trial-Evaluating-KEYTRUDA%C2%AE-pembrolizumab-Plus-Enzalutamide-and-Androgen-Deprivation-Therapy-in-Patients-With-Metastatic-Hormone-Sensitive-Prostate-Cancer-to-Stop-for-Futility Merck…today announced that it will stop the Phase 3 KEYNOTE-991 trial investigating KEYTRUDA…in combination with enzalutamide and androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC).
…At the interim analysis, KEYTRUDA in combination with enzalutamide [Xtandi] and ADT did not demonstrate an improvement in overall survival (OS) or radiographic progression-free survival (rPFS), the trial’s dual primary endpoints, compared to placebo plus enzalutamide and ADT. This is Keytruda’s third recent phase-3 in prostate cancer. In the KEYNOTE-921 trial, which reported results in Aug 2021, Keytruda failed to show a statsig benefit when added to chemo in CRPC (#msg-169574792). In the KEYLINK-010 study, which reported results in Mar 2022, the combination of Keytruda and Lynparza (a PARP inhibitor) failed to show a statisig benefit compared to Xtandi or Zytiga in mCPRC refractory to chemo and either of Xtandi or Zytiga (https://www.clinicaltrials.gov/ct2/show/NCT03834519 ).
Keytruda is a great drug, but it’s not invincible.
DewDiligence
2 years ago
MRK/MRNA cancer vaccine shines in adjuvant melanoma (RFS HR=0.56):
https://www.accesswire.com/731571/Moderna-and-Merck-Announce-mRNA-4157V940-an-Investigational-Personalized-mRNA-Cancer-Vaccine-in-Combination-with-KEYTRUDAR-pembrolizumab-Met-Primary-Efficacy-Endpoint-in-Phase-2b-KEYNOTE-942-Trial …the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial of mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with KEYTRUDA…demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of recurrence-free survival (RFS) versus KEYTRUDA alone for the adjuvant treatment of patients with stage III/IV melanoma following complete resection.
Adjuvant treatment with mRNA-4157/V940 in combination with KEYTRUDA reduced the risk of recurrence or death by 44% (HR=0.56 [95% CI, 0.31-1.08]; one-sided p-value=0.0266) compared with KEYTRUDA alone. Note: If this had been a phase-3 trial, it would’ve been considered a failure since the standard cutoff for a one-sided p-value is 0.025. For a phase-2b, however, these results are just fine.
DewDiligence
2 years ago
Lagevrio misses_primary_endpoint_in_large_Oxford_U_trial:
https://ca.finance.yahoo.com/news/merck-ridgeback-biotherapeutics-clinical-non-235000071.html The PANORAMIC study, a UK-based clinical trial sponsored by the University of Oxford, included 25,783 participants who were randomized to open label treatment with LAGEVRIO plus usual care (n=12,821) or usual care alone (n=12,962); mean age of participants was 56.6 years. Primary outcome data were available in 25,000 (97%) participants. Nearly all (>98%) participants were vaccinated, with approximately 95% receiving three or more doses of a SARS-CoV-2 vaccine.
In the preliminary analysis, the primary endpoint of reduction of hospitalizations and deaths within 28 days of randomization, compared to usual care, was not met; 0.8% of patients in both the LAGEVRIO group (n=103/12,516) and the usual care group (n=96/12,484) were hospitalized or died in the first 28 days. Separately, in a retrospective study based on electronic medical records of high-risk patients in Israel, Lagevrio showed a benefit in reducing hospitalizations and death in the patients age 65+ but not in patients age 40-64.
Bottom line: Legevrio (molnupiravir) remains a poor choice for treating COVID. It is being prescribed only when Paxlovid is either unavailable or contra-indicated due to drug-drug interactions (from ritonavir).
DewDiligence
2 years ago
Keytruda narrowly_misses_statsig OS/PFS as_addend_to Lenvina in_ first-line HCC:
https://finance.yahoo.com/news/merck-eisai-present-results-phase-063000955.html
In the final analysis of the trial, there was a trend toward improvement for one of the study’s dual primary endpoints, overall survival (OS), for patients treated with KEYTRUDA plus LENVIMA versus LENVIMA monotherapy; however, the results did not meet statistical significance per the pre-specified statistical plan (HR=0.84 [95% CI: 0.71-1.00]; p=0.0227). The median OS was 21.2 months (95% CI: 19.0-23.6) for KEYTRUDA plus LENVIMA and 19.0 months (95% CI: 17.2-21.7) for LENVIMA monotherapy.
Additionally, treatment with KEYTRUDA plus LENVIMA resulted in a trend toward improvement in the trial’s other dual primary endpoint of progression-free survival (PFS) versus LENVIMA monotherapy; however, the results did not meet the pre-specified threshold at the first interim analysis for statistical significance (HR=0.87 [95% CI: 0.73-1.02]; p=0.0466). These results were presented at ESMO.
DewDiligence
2 years ago
FDA approves MRK’s pneumococcal vaccine, Vaxneuvance for infants/children:
https://finance.yahoo.com/news/u-fda-approves-merck-vaxneuvance-104500312.html
Vaxneuvance was already FDA-approved for adults (#msg-164961310), but I don’t think Vaxneuvance will compete effectively with PFE’s Prevnar-20, which has broader coverage of pneumococcal serotypes and a simpler (one-shot) treatment course (#msg-166441188).
PFE's Prevnar-20 is FDA approved for adults, but is not yet approved for infants/children, so MRK does have a head start in the pediatric market.
MRK pays PFE a royalty of 7.25% on worldwide Vaxneuvance sales during 2022-2026 and a 2.5% royalty during 2027-2035 (#msg-166075692).
DewDiligence
2 years ago
MRK’s V116—(follow-on_to Vaxneuvance)—receives FDA BTD for prevention of pneumococcal disease in adults:
https://finance.yahoo.com/news/merck-announces-u-fda-granted-104500278.html
The phase-3 trial is expected to start during 2022.
V116 is a 21-valent vaccine; the 21 strains are: 3, 6A/C, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B/C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B.